A Randomized Phase 2 Trial to Evaluate the Efficacy of BCL-2 Inhibitor Therapy With Chemotherapy Compared to Chemotherapy Alone in Adult Patients With Newly Diagnosed T-Cell ALL and T-Cell Lymphoblastic Lymphoma

This phase II trial tests the safety and effectiveness of giving chemotherapy with or without venetoclax and/or navitoclax for the treatment of patients with newly diagnosed T-cell acute lymphoblastic leukemia (T-ALL) or T-cell lymphoblastic lymphoma (T-LBL). Chemotherapy drugs work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Venetoclax and navitoclax are in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. They may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving chemotherapy with or without venetoclax and/or navitoclax may be effective treatments for patients with newly diagnosed T-ALL or T-LBL.

Start Date09 Aug 2024

Sponsor / Collaborator

National Cancer Institute

NCT06317662 / Not yet recruitingPhase 2IIT

A Phase 2 Study of Blinatumomab in Combination With Chemotherapy for Infants With Newly Diagnosed Acute Lymphoblastic Leukemia With Randomization of KMT2A-Rearranged Patients to Addition of Venetoclax

This phase II trial tests the addition of venetoclax and/or blinatumomab to usual chemotherapy for treating infants with newly diagnosed acute lymphoblastic leukemia (ALL) with a KMT2A gene rearrangement (KMT2A-rearranged [R]) or without a KMT2A gene rearrangement (KMT2A-germline [G]). Venetoclax is in a class of medications called B-cell lymphoma-2 (Bcl-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Blinatumomab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Chemotherapy drugs work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Adding venetoclax and/or blinatumomab to standard chemotherapy may be more effective at treating patients with ALL than standard chemotherapy alone, but it may also cause more side effects. This clinical trial evaluates the safety and effectiveness of adding venetoclax and/or blinatumomab to chemotherapy for the treatment of infants with KMT2A-R or KMT2A-G ALL.

Start Date31 Jul 2024

Sponsor / Collaborator

National Cancer Institute

NCT06124157 / Not yet recruitingPhase 3IIT

A Randomized International Phase 3 Trial of Imatinib and Chemotherapy With or Without Blinatumomab in Patients With Newly-Diagnosed Philadelphia Chromosome-Positive or Philadelphia Chromosome-Like ABL-Class B-Cell Acute Lymphoblastic Leukemia

This phase III trial compares the effect of the combination of blinatumomab with dasatinib and standard chemotherapy versus dasatinib and standard chemotherapy for treating patients with Philadelphia chromosome positive (PH+) or Philadelphia chromosome-like (Ph-Like) ABL-class B-Cell acute lymphoblastic leukemia (B-ALL). Blinatumomab is a bispecific antibody that binds to two different proteins-one on the surface of cancer cells and one on the surface of cells in the immune system. An antibody is a protein made by the immune system to help fight infections and other harmful processes/cells/molecules. Blinatumomab may bind to the cancer cell and a T cell (which plays a key role in the immune system's fighting response) at the same time. Blinatumomab may strengthen the immune system's ability to fight cancer cells by activating the body's own immune cells to destroy the tumor. Dasatinib is in a class of medications called tyrosine kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply, which may help keep cancer cells from growing. Giving blinatumomab and dasatinib in combination with standard chemotherapy may work better in treating patients with PH+ or Ph-Like ABL-class B-ALL compared to dasatinib and chemotherapy alone.

Start Date22 Jul 2024

Sponsor / Collaborator

National Cancer Institute

100 Clinical Results associated with Mercaptopurine

100 Translational Medicine associated with Mercaptopurine

100 Patents (Medical) associated with Mercaptopurine

5,506

Literatures (Medical) associated with Mercaptopurine

01 May 2024·Current drug safety

The Effect of Renal Replacement Therapy in a Patient with Mercaptopurine Toxicity: Time to Revise Guidelines

Author: Sikma, M A ; Derijks, L J J ; Annema, P A ; Quaedvlieg, H J L ; Bethlehem, C ; Borkent, M ; Polderman, F N ; Jonge, De H J M

Introduction::

Mercaptopurine, a thiopurine, is used in various disorders of immune regulation, such as autoimmune hepatitis. Thiopurine metabolism is complex with risk for overdosing, especially when metabolism is impaired by liver dysfunction. Hepatotoxicity may be due to mercaptopurine overdose and is often reversible after prompt cessation of the drug.

Case Presentation::

Treatment of thiopurine toxicity is mainly supportive and literature on enhanced elimination by renal replacement therapy is ambiguous.

Conclusion::

In this case of thiopurine toxicity, a patient with autoimmune hepatitis presents with abdominal pain, nausea, vomiting, and diarrhea. We show in this case report that renal replacement therapy had no effect on total body clearance of mercaptopurine.

01 Mar 2024·Pediatric blood & cancer

Bioequivalence study followed by model‐informed dose optimization of a powder for oral suspension of 6‐mercaptopurine

Article

Author: Joshi, Mahendra ; Gota, Vikram ; Arun, Bhavatharini ; Chinnaswamy, Girish ; Madki, Shivkumar ; Ivaturi, Vijay ; Banavali, Shripad ; Kakkar, Archana Khosa

Abstract:

Background:

6‐Mercaptopurine (6MP) is the mainstay chemotherapy for acute lymphoblastic leukemia (ALL) and is conventionally available as 50 mg tablets. A new 6MP powder for oral suspension (PFOS 10 mg/mL) was developed recently by IDRS Labs, India, intended for pediatric use. A comparative pharmacokinetics of PFOS with T. mercaptopurine was conducted to determine the dose equivalence.

Methods:

An open‐label, randomized, two‐treatment, two‐period, two‐sequence, single oral dose, crossover, bioequivalence study was conducted on 51 healthy adult subjects. Post hoc, a population pharmacokinetic (PopPK) model was developed using the healthy volunteer data to perform simulations with various PFOS doses and select a bioequivalent dose. Further, to confirm the safety of PFOS in pediatrics, a simulation of 6MP and 6‐thioguanine exposures was performed by incorporating the formulation‐specific parameters derived from the healthy volunteer study into the PopPK model in childhood ALL available in literature.

Results:

The 6MP PFOS had 47% higher oral bioavailability compared to the reference product. Simulations using a two‐compartmental PopPK model with dissolution and transit compartments showed that 40 mg of PFOS was found to be equivalent to 50 mg tablets. The simulated 6‐thioguanine nucleotide concentrations in children using the dose adjusted for PFOS were between 114 and 703.6 pmol/8 × 108 RBC, which was within the range reported in pediatric ALL studies.

Conclusion:

6MP PFOS 10 mg/mL should be administered at a 20% lower dose than the tablet to achieve comparable exposure. 6MP PFOS addresses an unmet medical need for a liquid formulation of 6MP in the Indian subcontinent.

01 Feb 2024·Clinical pharmacology and therapeutics

Individualized Use of 6‐Mercaptopurine in Chinese Children with ALL: A Multicenter Randomized Controlled Trial

Article

Author: van den Anker, John ; Zhao, Bei-Bei ; Wu, Ke-Liang ; Ju, Xiu-Li ; Sun, Li-Rong ; Zhang, Li ; Yang, Fan ; Zhou, Yue ; Wang, Ling-Zhen ; Song, Chao ; Gu, Yan ; Li, Yun ; Wang, Hong-Mei ; Zhu, Xiao-Fan ; Xu, Hui-Juan ; Zhuang, Yong ; Zhao, Wei ; Liu, Xi-Ting ; Liang, Yu-Li ; Fu, Jin-Qiu ; Wang, Li

Continuous 6‐mercaptopurine (6‐MP) dose titration is necessary because of its narrow therapeutic index and frequently encountered dose‐limiting hematopoietic toxicity. However, evidence‐based guidelines for gene‐based 6‐MP dosing have not been established for Chinese children with acute lymphoblastic leukemia (ALL). This multicenter, randomized, open‐label, active‐controlled clinical trial randomly assigned Chinese children with low‐ or intermediate‐risk ALL in a 1:1 ratio to receive TPMT–NUDT15 gene–based dosing of 6‐MP (N = 44, 10 to 50 mg/m2/day) or standard dosing (N = 44, 50 mg/m2/day) during maintenance therapy. The primary end point was the incidence of 6‐MP myelosuppression in both groups. Secondary end points included frequencies of 6‐MP hepatotoxicity, duration of myelosuppression and leukopenia, event‐free survival, and steady‐state concentrations of active metabolites (6‐thioguaninenucleotides and 6‐methylmercaptopurine nucleotides) in erythrocytes. A 2.2‐fold decrease in myelosuppression, the primary end point, was observed in the gene‐based–dose group using ~ 50% of the standard initial 6‐MP dose (odds ratio, 0.26, 95% confidence interval, 0.11 to 0.64, P = 0.003). Patients in the gene‐based–dose group had a significantly lower risk of developing thiopurine‐induced myelosuppression and leukopenia (P = 0.015 and P = 0.022, respectively). No significant differences were observed in the secondary end points of the incidence of hepatotoxicity and steady‐state concentrations of active metabolites in erythrocytes between the two groups. TPMT‐ and NUDT15‐based dosing of 6‐MP will significantly contribute toward further reducing the incidence of leukopenia in Chinese children with ALL. This trial is registered at www.clinicaltrial.gov as #NCT04228393.

News (Medical) associated with Mercaptopurine

13 Jun 2024

·www.prnewswire.com

New CIMZIA® data for women living with chronic rheumatic diseases throughout pregnancy, and for people living with RA and high rheumatoid factor levels

Pharmacokinetic data from the CHERISH study suggest that pregnant women treated with certolizumab pegol can maintain their dosing regimen throughout pregnancy An in vitro study found that rheumatoid factor (RF) antibodies bind to Fc-containing tumor necrosis factor inhibitors (TNFis) but are not able to bind to Fc-free certolizumab pegol – providing molecular insights towards more personalized therapeutic approaches in rheumatoid arthritis (RA) A separate post hoc analysis of the phase 3b REALISTIC trial suggests that in high RF patients with RA treated with certolizumab pegol, clinical responses to certolizumab pegol were similar over time, regardless of RF level including in TNFi inadequate responders ATLANTA, June 13, 2024 /PRNewswire/ -- UCB, a global biopharmaceutical company, will present results from three studies for CIMZIA® (certolizumab pegol), a PEGylated fragment crystalized (Fc)-free tumor necrosis factor inhibitor (TNFi), for women of childbearing age living with chronic immune-mediated diseases and people with rheumatoid arthritis (RA) and high rheumatoid factor (RF) levels.1,2,3 These data will be presented at the European Congress of Rheumatology, EULAR 2024, and provide evidence to inform personalized treatment decisions for patient populations with high unmet need. CHERISH study results (abstract POS0888) Results from the open-label, phase 1b CHERISH study in women with immune-mediated diseases, including psoriatic arthritis (PsA), axial spondyloarthritis (axSpA), and RA, found that the range of blood plasma concentrations of certolizumab pegol throughout and after pregnancy were similar to those observed in studies of non-pregnant women with PsA, axSpA, and RA, suggesting that women may maintain stable therapeutic levels of certolizumab pegol throughout pregnancy.1 These data build on previous pharmacokinetic studies – CRIB and CRADLE – that showed minimal-to-no transfer from mother to baby through the placenta or breast milk.4,5 The latest study, CHERISH, expands on the data available by focusing on certolizumab pegol and stability of exposure for the mother.1 The safety profile observed in the CHERISH study was consistent with the known safety profile of certolizumab pegol, which includes extensive pharmacovigilance data.1 The CHERISH, CRIB, and CRADLE studies are pharmacokinetic studies. There are no adequate and well-controlled studies of CIMZIA in pregnant women or lactation to demonstrate efficacy or establish safety. "Women of childbearing age living with chronic immune-mediated diseases are understandably concerned about how to ensure adequate disease control throughout pregnancy while preventing or minimizing exposure for their baby," said Emmanuel Caeymaex, Executive Vice President, Head of Patient Impact, Chief Commercial Officer, UCB. "Through CHERISH and the full body of evidence we have built, we are equipping women and healthcare professionals with the data they need to make informed, personalized decisions around treatment continuation during family planning, pregnancy and breastfeeding. These studies underscore our commitment to serving specific subpopulations of patients with information that is directly relevant to them." RF-drug interaction research (abstract POS0722) A further study presented at EULAR provided molecular insights into why individuals living with RA and high RF levels generally maintain consistent drug concentrations and may experience consistent clinical outcomes when treated with certolizumab pegol.3,6 An in vitro study found that three different RF antibodies all bound to Fc-containing TNFi adalimumab and enabled the formation of large immune complexes. Conversely, the RFs were unable to interact with certolizumab pegol, due to its lack of Fc domain, and no complexes with RF were formed.3 REALISTIC trial results (abstract AB0638) Insights into the effects of certolizumab pegol in people living with RA and high RF levels were investigated in a post-hoc analysis of the double-blind, placebo controlled, phase 3b REALISTIC trial – also accepted as an abstract at EULAR. Clinical response to certolizumab pegol was analyzed according to the highest quartile RF level compared with the lowest and in people with a previous inadequate response to TNFi versus those with no prior TNFi exposure.2 Responses were greater with certolizumab pegol versus placebo in all groups. In patients who previously had an inadequate response to TNFis, responses among those who were randomized to placebo were lower in the high RF group compared with the low RF group at week 12. By contrast, clinical responses to certolizumab pegol treatment were similar between those with high and with low RF levels, indicating that RF level does not influence a patient's response to certolizumab pegol.2 "For people living with RA, high RF levels are associated with more severe disease activity, risk of progression and loss of treatment efficacy, so the encouraging results of the REALISTIC study may impact treatment choices for people living with RA and high RF levels who have previously had an inadequate response to TNFis," said Dr James Galloway, investigator on the REALISTIC trial, Professor of Rheumatology at King's College London and an honorary Consultant in Rheumatology at King's College Hospital, London. "The RF-drug interaction research also presented at EULAR provides important molecular insights in to why we see more consistent drug concentrations among high RF patients treated with certolizumab pegol compared with Fc-containing TNFis." These certolizumab pegol data together demonstrate how tailored treatment approaches can support specific groups of patients. Dr. Oseme Etomi, Consultant Rheumatologist and Obstetric Physician, Guy's and St Thomas Hospitals, London, said, "Chronic rheumatological diseases such as axSpA, RA, and PsA are multifactorial and present significant treatment challenges, particularly as patients progress through different stages of life, such as family planning, pregnancy and breastfeeding, or disease progression. The new clinical data we've seen at EULAR are valuable to support more personalized treatment that is tailored to the individual needs, lifestyle choices and clinical profile of each patient." For further information, contact UCB: Investor Relations Antje Witte T: +32.2.559.94.14 email [email protected] U.S. Communications Nicole Herga T: +1.773.960.5349 email [email protected] Notes to editors: About CHERISH1 The CHERISH study was a multicenter, longitudinal, interventional, prospective, open-label phase 1B exploratory study evaluating the impact of pregnancy on the pharmacokinetics of certolizumab pegol. The study consisted of a screening period, pregnancy period (up to 40 weeks), post-partum period (up to 13 weeks), and a safety follow-up contact (five weeks after final study visit). CHERISH investigated the blood concentrations of certolizumab pegol during and after pregnancy, alongside monitoring any adverse events. Twenty-one women, nine of them with rheumatoid arthritis, were enrolled into CHERISH when up to 10 weeks pregnant and having been on a stable maintenance dose of certolizumab pegol (either 200 mg or 400 mg every two weeks, or 400 mg every four weeks) for at least 12 weeks. Blood samples were taken pre-dose every four weeks during pregnancy and once at roughly 12 weeks post-partum, as well as one week after a certolizumab pegol dose every eight weeks during pregnancy and once post-partum. The participants were contacted for a safety follow-up after another five weeks. All observed concentrations of certolizumab pegol were within the range seen in non-pregnant patients with psoriatic arthritis, axial spondyloarthritis, and rheumatoid arthritis (1.7-45.3 µg/ml). Levels of certolizumab pegol remain consistent throughout pregnancy, although they were somewhat lower during pregnancy than post-partum. The adverse event profile was consistent with the known profile of certolizumab pegol, and no safety concerns were reported. The findings from CHERISH suggest that women may continue certolizumab pegol at their usual dose and expect to maintain stable therapeutic levels throughout pregnancy. About CRIB and CRADLE CRIB was a pharmacokinetic study of women ≥30 weeks pregnant receiving commercial certolizumab pegol for a locally approved indication (last dose ≤35 days prior to delivery). Blood samples were taken from mother, infant, and umbilical cord at birth, and again from the baby at four and eight weeks of age, to assess whether certolizumab pegol is transferred to infants via the placenta. Of the 16 women who participated, eleven were receiving certolizumab pegol for rheumatoid arthritis, three for Crohn's disease, one for psoriatic arthritis, and one for axial spondyloarthritis/ankylosing spondylitis; all had healthy pregnancies, and 14 of the babies gave samples that could be included in the study. Using a specific, sensitive assay, levels of certolizumab pegol in the mothers at delivery were found to be in the therapeutic range, whereas the level was below measurable in 13 of the newborns. In the fourteenth infant, a minimal level of certolizumab pegol was detected, equivalent to 0.09% of the maternal level and considered unlikely to have any effect. By weeks four and eight, certolizumab pegol was undetectable in all the babies. There were no patterns of adverse events in the babies to suggest any difference from children of mothers not treated with certolizumab pegol, while safety data in the mothers were consistent with the known profile of certolizumab pegol and of the underlying diseases in pregnancy. Thus, CRIB showed minimal to no placental transfer of certolizumab pegol from mother to infant, supporting continuation of treatment throughout pregnancy when clinically needed. CRADLE was a pharmacokinetic study of lactating mothers receiving certolizumab pegol. The study assessed whether certolizumab pegol is transferred into breast milk and the level of dose an infant might be exposed to. The 17 women involved were receiving certolizumab pegol (seven for rheumatoid arthritis, five for Crohn's disease, three for psoriatic arthritis, and two for axial spondyloarthritis/ankylosing spondylitis) and had chosen to breastfeed – both decisions were made independent of the study. Mothers provided milk samples during at-home visits starting at least six weeks post-partum, to allow breastfeeding routine to be established undisturbed, beginning with a pre-dose sample on the day of their certolizumab pegol dose, and then every two days for two weeks. One mother on a four-week dose schedule gave one additional pre-dose sample at four weeks. Certolizumab pegol levels were below measurable in 77 of 137 milk samples tested (56%), while the remainder had minimal levels, all less than 1% of the expected level in the blood of an adult receiving a therapeutic maintenance dose. A relative infant dose (RID) below 10% is considered unlikely to be of concern to infant wellbeing. The mean RID for certolizumab pegol was calculated to be below 0.5% of the maternal dose and the median RID was 0.15%. Adverse events in the infants of mothers treated with certolizumab pegol were consistent with those occurring in unexposed infants of similar age, while those in the mothers were consistent with the known safety profile of certolizumab pegol. With results indicating minimal to no transfer into breast milk, CRADLE showed that continued treatment with certolizumab pegol is compatible with breastfeeding. About REALISTIC2 REALISTIC (RA Evaluation in Subjects Receiving TNF Inhibitor Certolizumab Pegol) was a multicenter phase 3b trial in patients with active rheumatoid arthritis who had shown inadequate response to disease-modifying antirheumatic drugs, including patients with/without prior TNFi exposure, with/without concomitant methotrexate or other disease-modifying anti-rheumatic drugs (DMARDs);), and varying lengths of disease duration. The study demonstrated that – in a diverse group of RA patients reflecting those seen in daily clinical practice (including those with prior TNF-inhibitor use) – addition of certolizumab pegol to current therapy was associated with a rapid and consistent clinical response, including improved physical function and reduced disease activity. Patients with active RA with inadequate response to ≥1 DMARD were randomized 4:1 to subcutaneous injections of certolizumab pegol 400 mg at Weeks 0, 2, and 4 followed by 200 mg every 2 weeks or placebo injection (control) every 2 weeks + current therapy. Primary outcome was ACR20 at Week 12. Randomization was stratified by prior TNF inhibitor use, concomitant use of methotrexate (MTX), and disease duration (<2 y vs ≥2 y). About CIMZIA® in the U.S.7 CIMZIA® is the only Fc-free, PEGylated anti-TNF (tumor necrosis factor). CIMZIA has a high affinity for human TNF-alpha, selectively neutralizing the pathophysiological effects of TNF-alpha. CIMZIA is also indicated for the treatment of adults with moderately to severely active rheumatoid arthritis (RA), adults with active psoriatic arthritis (PsA), adults with active ankylosing spondylitis (AS), and adults with active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation. CIMZIA is indicated for the treatment of moderate-to-severe plaque psoriasis (PSO) in adults who are candidates for systemic therapy or phototherapy. In addition, CIMZIA is indicated for reducing signs and symptoms of Crohn's disease (CD) and maintaining clinical response in adult patients with moderately to severely active disease who have had an inadequate response to conventional therapy. See important safety information including risk of serious bacterial, viral and fungal infections and tuberculosis below. IMPORTANT SAFETY INFORMATION about CIMZIA in the U.S. CONTRAINDICATIONS CIMZIA is contraindicated in patients with a history of hypersensitivity reaction to certolizumab pegol or to any of the excipients. Reactions have included angioedema, anaphylaxis, serum sickness, and urticaria. SERIOUS INFECTIONS Patients treated with CIMZIA are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. Discontinue CIMZIA if a patient develops a serious infection or sepsis. Reported infections include: Active tuberculosis (TB), including reactivation of latent TB. Patients with TB have frequently presented with disseminated or extrapulmonary disease. Test patients for latent TB before CIMZIA use and during therapy. Initiate treatment for latent TB prior to CIMZIA use. Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized, disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Consider empiric anti-fungal therapy in patients at risk for invasive fungal infections who develop severe systemic illness. Bacterial, viral, and other infections due to opportunistic pathogens, including Legionella and Listeria. Carefully consider the risks and benefits of treatment with CIMZIA prior to initiating therapy in the following patients: with chronic or recurrent infection; who have been exposed to TB; with a history of opportunistic infection; who resided in or traveled in regions where mycoses are endemic; with underlying conditions that may predispose them to infection. Monitor patients closely for the development of signs and symptoms of infection during and after treatment with CIMZIA, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy. Do not start CIMZIA during an active infection, including localized infections. Patients older than 65 years, patients with co-morbid conditions, and/or patients taking concomitant immunosuppressants may be at greater risk of infection. If an infection develops, monitor carefully and initiate appropriate therapy. MALIGNANCY Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, of which CIMZIA is a member. CIMZIA is not indicated for use in pediatric patients. Consider the risks and benefits of CIMZIA treatment prior to initiating or continuing therapy in a patient with known malignancy. In clinical trials, more cases of malignancies were observed among CIMZIA-treated patients compared to control patients. In CIMZIA clinical trials, there was an approximately 2-fold higher rate of lymphoma than expected in the general U.S. population. Patients with rheumatoid arthritis, particularly those with highly active disease, are at a higher risk of lymphoma than the general population. Malignancies, some fatal, have been reported among children, adolescents, and young adults being treated with TNF blockers. Approximately half of the cases were lymphoma, while the rest were other types of malignancies, including rare types associated with immunosuppression and malignancies not usually seen in this patient population. Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers, including CIMZIA. These cases have had a very aggressive disease course and have been fatal. The majority of reported TNF blocker cases have occurred in patients with Crohn's disease or ulcerative colitis, and the majority were in adolescent and young adult males. Almost all of these patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with a TNF blocker at or prior to diagnosis. Carefully assess the risks and benefits of treating with CIMZIA in these patient types. Cases of acute and chronic leukemia were reported with TNF blocker use. HEART FAILURE Worsening and new onset congestive heart failure (CHF) has been reported with TNF blockers. Exercise caution and monitor carefully. HYPERSENSITIVITY Angioedema, anaphylaxis, dyspnea, hypotension, rash, serum sickness, and urticaria have been reported following CIMZIA administration. If a serious allergic reaction occurs, stop CIMZIA and institute appropriate therapy. The needle shield inside the removable cap of the CIMZIA prefilled syringe contains a plastic derivative of natural rubber latex which may cause an allergic reaction in individuals sensitive to latex. HEPATITIS B VIRUS REACTIVATION Use of TNF blockers, including CIMZIA, may increase the risk of reactivation of hepatitis B virus (HBV) in patients who are chronic carriers. Some cases have been fatal. Test patients for HBV infection before initiating treatment with CIMZIA. Exercise caution in patients who are carriers of HBV and monitor them before and during CIMZIA treatment. Discontinue CIMZIA and begin antiviral therapy in patients who develop HBV reactivation. Exercise caution when resuming CIMZIA after HBV treatment. Abbreviations: HBV: hepatitis B, RA: rheumatoid arthritis, RF: rheumatoid factor, TNF: tumor necrosis factor. NEUROLOGIC REACTIONS TNF blockers, including CIMZIA, have been associated with rare cases of new onset or exacerbation of central nervous system and peripheral demyelinating diseases, including multiple sclerosis, seizure disorder, optic neuritis, peripheral neuropathy, and Guillain-Barré syndrome. HEMATOLOGIC REACTIONS Rare reports of pancytopenia, including aplastic anemia, have been reported with TNF blockers. Medically significant cytopenia has been infrequently reported with CIMZIA. Consider stopping CIMZIA if significant hematologic abnormalities occur. DRUG INTERACTIONS Do not use CIMZIA in combination with other biological DMARDS. AUTOIMMUNITY Treatment with CIMZIA may result in the formation of autoantibodies and, rarely, in development of a lupus-like syndrome. Discontinue treatment if symptoms of a lupus-like syndrome develop. IMMUNIZATIONS Patients on CIMZIA should not receive live or live-attenuated vaccines. ADVERSE REACTIONS The most common adverse reactions in CIMZIA clinical trials (≥8%) were: upper respiratory infections (18%), rash (9%), and urinary tract infections (8%). For full prescribing information, please visit . Abbreviations: ACR: American College of Rheumatology, AS: ankylosing spondylitis; axSpA: axial spondyloarthritis, CD28: cluster of differentiation 28 (a protein expressed on T cells), CRP: C-reactive protein, DMARDs: disease-modifying antirheumatic drugs, EEA: European Economic Area, EU: European Union, HBV: hepatitis B virus, MRI: magnetic resonance imaging, MTX: methotrexate, NSAIDs: non-steroidal anti-inflammatory drugs, RA: rheumatoid arthritis, RF: rheumatoid factor, TNFis: tumor necrosis factor inhibitors. About UCB UCB, Brussels, Belgium () is a global biopharmaceutical company focused on the discovery and development of innovative medicines and solutions to transform the lives of people living with severe diseases of the immune system or of the central nervous system. With approximately 9,000 people in approximately 40 countries, the company generated revenue of €5.3 billion in 2023. UCB is listed on Euronext Brussels (symbol: UCB). Follow us on Twitter: @UCB_USA. Forward looking statements This press release may contain forward-looking statements including, without limitation, statements containing the words "believes", "anticipates", "expects", "intends", "plans", "seeks", "estimates", "may", "will", "continue" and similar expressions. These forward-looking statements are based on current plans, estimates and beliefs of management. All statements, other than statements of historical facts, are statements that could be deemed forward-looking statements, including estimates of revenues, operating margins, capital expenditures, cash, other financial information, expected legal, arbitration, political, regulatory or clinical results or practices and other such estimates and results. By their nature, such forward-looking statements are not guarantees of future performance and are subject to known and unknown risks, uncertainties and assumptions which might cause the actual results, financial condition, performance or achievements of UCB, or industry results, to differ materially from those that may be expressed or implied by such forward-looking statements contained in this press release. Important factors that could result in such differences include: changes in general economic, business and competitive conditions, the inability to obtain necessary regulatory approvals or to obtain them on acceptable terms or within expected timing, costs associated with research and development, changes in the prospects for products in the pipeline or under development by UCB, effects of future judicial decisions or governmental investigations, safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, product liability claims, challenges to patent protection for products or product candidates, competition from other products including biosimilars, changes in laws or regulations, exchange rate fluctuations, changes or uncertainties in tax laws or the administration of such laws, and hiring and retention of its employees. There is no guarantee that new product candidates will be discovered or identified in the pipeline, will progress to product approval or that new indications for existing products will be developed and approved. Movement from concept to commercial product is uncertain; preclinical results do not guarantee safety and efficacy of product candidates in humans. So far, the complexity of the human body cannot be reproduced in computer models, cell culture systems or animal models. The length of the timing to complete clinical trials and to get regulatory approval for product marketing has varied in the past and UCB expects similar unpredictability going forward. Products or potential products, which are the subject of partnerships, joint ventures or licensing collaborations may be subject to differences disputes between the partners or may prove to be not as safe, effective or commercially successful as UCB may have believed at the start of such partnership. UCB's efforts to acquire other products or companies and to integrate the operations of such acquired companies may not be as successful as UCB may have believed at the moment of acquisition. Also, UCB or others could discover safety, side effects or manufacturing problems with its products and/or devices after they are marketed. The discovery of significant problems with a product similar to one of UCB's products that implicate an entire class of products may have a material adverse effect on sales of the entire class of affected products. Moreover, sales may be impacted by international and domestic trends toward managed care and health care cost containment, including pricing pressure, political and public scrutiny, customer and prescriber patterns or practices, and the reimbursement policies imposed by third-party payers as well as legislation affecting biopharmaceutical pricing and reimbursement activities and outcomes. Finally, a breakdown, cyberattack or information security breach could compromise the confidentiality, integrity and availability of UCB's data and systems. Given these uncertainties, you should not place undue reliance on any of such forward-looking statements. There can be no guarantee that the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labelling in any market, or at any particular time, nor can there be any guarantee that such products will be or will continue to be commercially successful in the future. UCB is providing this information, including forward-looking statements, only as of the date of this press release. UCB expressly disclaims any duty to update any information contained in this press release, either to confirm the actual results or to report or reflect any change in its forward-looking statements with regard thereto or any change in events, conditions or circumstances on which any such statement is based, unless such statement is required pursuant to applicable laws and regulations. Additionally, information contained in this document shall not constitute an offer to sell or the solicitation of an offer to buy any securities, nor shall there be any offer, solicitation or sale of securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of such jurisdiction. References 1 Clowse ME, et al. Pharmacokinetics of certolizumab pegol in pregnancy: results from the open-label, phase 1b CHERISH study. EULAR, Vienna, 12-15 June 2024. Abstract POS0888. 2 Smolen JS, et al. Do high rheumatoid factor levels impact response to certolizumab pegol in patients with inadequately controlled rheumatoid arthritis? A post hoc analysis of the phase 3b REALISTIC trial. EULAR, Vienna, 12-15 June 2024. Abstract number AB0638. 3 Bidgood SR, et al. Purified monoclonal rheumatoid factors bind Fc containing TNF inhibitors in vitro but not the Fc-free TNF inhibitor, certolizumab pegol. EULAR, Vienna, 12-15 June 2024. Abstract POS0722. 4 Mariette X, et al. Lack of placental transfer of certolizumab pegol during pregnancy: results from CRIB, a prospective, postmarketing, pharmacokinetic study. Ann Rheum Dis. 2018;77(2):228-33. 5 Clowse ME, et al. Minimal to no transfer of certolizumab pegol into breast milk: results from CRADLE, a prospective, postmarketing, multicentre, pharmacokinetic study. Ann Rheum Dis. 2017;76(11):1890-6. 6 Smolen J, et al. Do High RF Titers Impact Response to TNF Inhibitors? Comparison of Certolizumab Pegol and Adalimumab in Patients with RA and High Titers of RF: A Post Hoc Analysis of a Phase 4 Trial. Rheumatology. 2024;63(suppl 1):75-76. 7 CIMZIA (certolizumab pegol) [prescribing information]. Smyrna, GA: UCB, Inc. US-CZ-2400269 CIMZIA® is a registered trademark of the UCB Group of Companies. ©2024 UCB, Inc., Smyrna, GA 30080. All rights reserved. Date of preparation: June 2024 SOURCE UCB

Clinical ResultPhase 3Phase 1

21 May 2024

·www.prnewswire.com

ZYMFENTRA™ (infliximab-dyyb) demonstrated long-term efficacy and safety profile of maintenance treatment through two years for adults with moderately to severely active Crohn's disease and ulcerative colitis

Findings from the extended LIBERTY studies and associated post-hoc analysis support the long-term efficacy and safety of ZYMFENTRA™, the first and only FDA-approved subcutaneous infliximab[1],[2] Data from a post-hoc analysis of the LIBERTY-CD study showed that, despite affecting drug levels, anti-drug antibodies (ADAs) status appeared to have no significant impact on W54 clinical outcomes or discontinuation rates [3] JERSEY CITY, N.J., May 21, 2024 /PRNewswire/ -- Celltrion USA announced today positive two-year results from the extended LIBERTY studies (LIBERTY-CD and LIBERTY-UC) for ZYMFENTRA™ (infliximab-dyyb) in adult patients with moderately to severely active Crohn's disease (CD) and ulcerative colitis (UC) after induction with intravenous (IV) infliximab, further supporting the efficacy and safety seen in previous pivotal studies. The data was shared during 18 oral and poster presentations at the Digestive Disease Week® (DDW) 2024 Annual Meeting in Washington, D.C., from May 18 to 21. The presentations included results of the two-year LIBERTY studies and a post-hoc analysis of the LIBERTY-CD study, which evaluated the impact of anti-drug antibodies (ADAs) on drug levels and efficacy in patients treated with ZYMFENTRA. "Establishing the long-term efficacy and safety profile of ZYMFENTRA is an important step as we work to bring relief and remission to the millions of people worldwide living with Crohn's disease and ulcerative colitis," said Thomas Nusbickel, Chief Commercial Officer at Celltrion USA. "These studies reaffirm efficacy and tolerance of ZYMFENTRA as maintenance therapy and underscore Celltrion USA's commitment to delivering different treatment options for patients in the gastroenterology space." Two-year extension phase of LIBERTY studies The extension phase of the LIBERTY studies (LIBERTY-CD and LIBERTY-UC) was carried out over a duration of 102 weeks (including 10 weeks of infliximab IV induction), expanding upon the initial LIBERTY trials. These two-year studies evaluated the long-term efficacy and safety of infliximab SC in patients diagnosed with Crohn's disease (CD) and ulcerative colitis (UC). In both LIBERTY-CD and UC studies, efficacy results, including but not limited to clinical remission, clinical response and corticosteroid-free remission, were generally well maintained at Week 102 compared to those of Week 54. Post-hoc analysis of LIBERTY-CD study A post-hoc analysis evaluated the impact of ADAs on clinical outcomes in patients with CD who received infliximab SC maintenance treatment. The analysis comprised 231 patients (ADA-positive: n=150; ADA-negative: n=81) who received infliximab SC as maintenance treatment. Notably, there were no statistically significant differences in clinical outcomes at Week 54 between ADA-positive and ADA-negative patients. Although mean trough serum infliximab concentrations at Week 54 were notably lower in the ADA-positive group than in the ADA-negative group (11.7 vs. 19.3 μg/mL; p<0.00001), both groups exceeded the historical therapeutic target concentration of 5 μg/mL, with comparable discontinuation rates observed between the groups. "Results from the two-year extension phase LIBERTY studies, alongside post-hoc analysis, highlight important data supporting the efficacy and safety of ZYMFENTRA as a subcutaneous maintenance treatment option for people living with CD and UC," said Hetal Patel, Senior Director, Medical Affairs at Celltrion USA. "The post-hoc analysis reveals that ADAs showed no significant impact on clinical outcomes or discontinuation rates. These findings could be explained by the relatively high trough serum infliximab concentrations achieved by ADA-positive patients."[1],[2],[3] PEREM long term study In a large multi-center prospective cohort of inflammatory bowel diseases, the study assessed SC infliximab persistence, efficacy and tolerance after the switch from intravenous infliximab. The study enrolled 426 patients, with 72.4% diagnosed with Crohn's disease (CD). At baseline, 74% of participants were receiving the standard IV infliximab dose (5 mg/kg every 8 weeks), with 16% receiving combination therapy with an immunosuppressant. Drug persistence with SC infliximab was notably high at 95.3% among patients with complete data up to Week 48 (95% confidence interval: 93.2-97.5)[4] About Celltrion USA Celltrion USA is Celltrion's U.S. subsidiary established in 2018. Headquartered in New Jersey, Celltrion USA is committed to expanding access to innovative biologics to improve care for U.S. patients. Celltrion currently has five biosimilars approved by the U.S. FDA: INFLECTRA® (infliximab-dyyb), TRUXIMA® (rituximab-abbs), HERZUMA® (trastuzumab-pkrb), VEGZELMA® (bevacizumab-adcd) and YUFLYMA®(adalimumab-aaty) as well as a new biologic ZYMFENTRA™. Celltrion USA will continue to leverage Celltrion's unique heritage in biotechnology, supply chain excellence and best-in-class sales capabilities to improve access to high-quality biopharmaceuticals for U.S. patients. For more information, please visit: . About Digestive Disease Week ® Digestive Disease Week® (DDW) is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE) and the Society for Surgery of the Alimentary Tract (SSAT), DDW is an in-person and online meeting from May 18-21, 2024. The meeting showcases more than 4,400 abstracts and hundreds of lectures on the latest advances in GI research, medicine and technology. More information can be found at About ZYMFENTRA ™ (infliximab-dyyb) ZYMFENTRA is a prescription medicine used as an injection under the skin (subcutaneous injection) by adults for the maintenance treatment of: Moderately to severely active ulcerative colitis following treatment with an infliximab product given by intravenous infusion (IV) and moderately to severely active Crohn's disease following treatment with an infliximab product given by intravenous infusion (IV). ZYMFENTRA blocks the action of tumor necrosis factor-alpha (TNF-alpha), a protein that can be overproduced in response to certain diseases and cause the immune system to attack normal, healthy parts of the body. ZYMFENTRA (infliximab-dyyb) was approved by the FDA through the Biologics License Application (BLA) under the 351 (a) pathway of the Public Health Service Act (a "stand-alone" BLA). ZYMFENTRA is a self-injected form of infliximab and thus will be under patent protection for its dosage form by 2037 and for its route of administration by 2040. ZYMFENTRA™ (infliximab-dyyb) U.S. Use and Important Safety Information ZYMFENTRA is a prescription medicine indicated in adults for maintenance treatment of: Moderately to severely active Crohn's disease following treatment with an infliximab product administered intravenously. Moderately to severely active ulcerative colitis following treatment with an infliximab product administered intravenously. It is not known if ZYMFENTRA is safe and effective in children under 18 years of age. What is the most important information I should know about ZYMFENTRA? SERIOUS INFECTIONS Patients treated with ZYMFENTRA are at increased risk for developing serious infections involving various organ systems and sites that may lead to hospitalization or death. Discontinue ZYMFENTRA if a patient develops a serious infection or sepsis. Reported infections include: Active tuberculosis (TB), including reactivation of latent TB. Patients frequently presented with disseminated or extrapulmonary disease. Patients should be tested for latent TB before and during treatment with ZYMFENTRA. Treatment for latent infection should be initiated prior to treatment with ZYMFENTRA. Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients may present with disseminated, rather than localized, disease. Empiric anti-fungal therapy should be considered in patients at risk for invasive fungal infections who develop severe systemic illness. Bacterial, viral, and other infections due to opportunistic pathogens, including Legionella and Listeria. The risks and benefits of treatment with ZYMFENTRA should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection. Closely monitor patients for the development of signs and symptoms of infection during and after treatment with ZYMFENTRA, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy. Risk of infection may be higher in patients greater than 65 years of age, patients with comorbid conditions and/or patients taking concomitant immunosuppressant therapy. In clinical trials, other serious infections observed in patients treated with infliximab included arthritis bacterial, pneumonia, and urinary tract infection. MALIGNANCIES Malignancies, some fatal, have been reported in children, adolescents, and young adults treated with TNF blockers, including infliximab products. Approximately half of these cases were lymphomas, including Hodgkin's and non-Hodgkin's lymphoma. The other cases represented a variety of malignancies, including rare malignancies that are usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents. The malignancies occurred after a median of 30 months after the first dose of therapy. Most of the patients were receiving concomitant immunosuppressants. Post-marketing cases of hepatosplenic T-cell lymphoma, a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers, including infliximab products. These cases have had a very aggressive disease course and have been fatal. The majority of reported cases have occurred in patients with Crohn's disease or ulcerative colitis, and most were in adolescent and young adult males. Almost all of these patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with a TNF blocker at or prior to diagnosis. Carefully assess the risks and benefits of treatment with ZYMFENTRA, especially in these patient types. In clinical trials of all TNF blockers, more cases of malignancies were observed compared with controls and the expected rate in the general population. In clinical trials of some TNF blockers, including infliximab products, more cases of other malignancies were observed compared with controls. As the potential role of TNF blocker therapy in the development of malignancies is not known, caution should be exercised when considering treatment of patients with a current or a past history of malignancy. Melanoma and Merkel cell carcinoma have been reported in patients treated with TNF blocker therapy, including infliximab products. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer. CONTRAINDICATIONS ZYMFENTRA is contraindicated in patients with a previous severe hypersensitivity reaction to infliximab-dyyb, other infliximab products, any of the inactive ingredients of ZYMFENTRA or any murine proteins (severe hypersensitivity reactions have included anaphylaxis, hypotension, and serum sickness). HEPATITIS B VIRUS REACTIVATION TNF blockers, including infliximab products, have been associated with reactivation of hepatitis B virus (HBV) in patients who are chronic carriers. Some cases were fatal. Patients should be tested for HBV infection before initiating ZYMFENTRA. For patients who test positive, consult a physician with expertise in the treatment of hepatitis B. Exercise caution when prescribing ZYMFENTRA for patients identified as carriers of HBV, and monitor closely for active HBV infection during and following termination of therapy with ZYMFENTRA. Discontinue ZYMFENTRA in patients who develop HBV reactivation and initiate antiviral therapy with appropriate supportive treatment. Exercise caution when considering resumption of ZYMFENTRA, and monitor patients closely. HEPATOTOXICITY Hepatobiliary disorders, including acute liver failure, jaundice abnormal hepatic function, hepatic steatosis, hepatitis, hepatotoxicity, hyperbilirubinemia, and non-alcoholic fatty liver, have been reported in patients receiving infliximab products post-marketing. Some cases were fatal or required liver transplant. Aminotransferase elevations were not noted prior to discovery of liver injury in many cases. Patients with symptoms or signs of liver dysfunction should be evaluated for evidence of liver injury. If jaundice and/or marked liver enzyme elevations (eg, ≥5 times the upper limit of normal) develop, ZYMFENTRA should be discontinued, and a thorough investigation of the abnormality should be undertaken. CONGESTIVE HEART FAILURE Cases of worsening congestive heart failure (CHF) and new onset CHF have been reported with TNF blockers. Some cases had a fatal outcome. In several exploratory trials of other TNF blockers in the treatment of CHF, there were greater proportions of TNF-blocker-treated patients who had CHF exacerbations requiring hospitalization or increased mortality. ZYMFENTRA has not been studied in patients with a history of CHF and ZYMFENTRA should be used with caution in patients with CHF. HEMATOLOGIC REACTION Cases of leukopenia, neutropenia, thrombocytopenia, and pancytopenia (some fatal) have been reported. The causal relationship to infliximab-product therapy remains unclear. Exercise caution in patients who have ongoing or a history of significant hematologic abnormalities. Advise patients to seek immediate medical attention if they develop signs and symptoms of blood dyscrasias or infection. Consider discontinuation of ZYMFENTRA in patients who develop significant hematologic abnormalities. HYPERSENSITIVITY AND OTHER ADMINISTRATION REACTIONS In post-marketing experience, serious systemic hypersensitivity reactions (including anaphylaxis, hypotension, and serum sickness) have been reported following administration of infliximab products. If an anaphylactic or other clinically significant hypersensitivity reaction occurs, institute appropriate therapy and discontinue ZYMFENTRA. INJECTION SITE REACTIONS In clinical studies, localized injection-site reactions were reported following administration of ZYMFENTRA. If a clinically significant injection-site reaction occurs, institute appropriate therapy and discontinue ZYMFENTRA. NEUROLOGIC REACTIONS Agents that inhibit TNF have been associated with central nervous system (CNS) manifestation of systemic vasculitis, seizure, and new onset or exacerbation of CNS demyelinating disorders, including multiple sclerosis and optic neuritis, and peripheral demyelinating disorders, including Guillain-Barré syndrome. Exercise caution when considering ZYMFENTRA in patients with these disorders and consider discontinuation if these disorders develop. RISK OF INFECTION WITH CONCURRENT ADMINISTRATION OF OTHER BIOLOGICS PRODUCTS Serious infections and neutropenia have been reported with concurrent use of ZYMFENTRA with other immunosuppressive biological products. The concurrent use of ZYMFENTRA with other immunosuppressive biological products used to treat UC and CD may increase the risk of infection and is not recommended. RISK OF ADDITIVE IMMUNOSUPPRESSIVE EFFECTS FROM PRIOR BIOLOGICAL PRODUCTS Consider the half-life and mode of action of prior biological products to avoid unintended additive immunosuppressive effects when initiating ZYMFENTRA. AUTOIMMUNITY Treatment with TNF blockers may result in the formation of autoantibodies and in the development of a lupus-like syndrome. Discontinue ZYMFENTRA treatment if symptoms of a lupus-like syndrome develop. VACCINATIONS AND USE OF LIVE VACCINES/THERAPEUTIC INFECTIOUS AGENTS Prior to initiating ZYMFENTRA, update vaccinations in accordance with current vaccination guidelines. Live vaccines or therapeutic infectious agents should not be given with ZYMFENTRA due to the possibility of clinical infections, including disseminated infections. At least a 6-month waiting period following birth is recommended before the administration of any live vaccine to infants exposed in utero to ZYMFENTRA. ADVERSE REACTIONS In clinical trials with ZYMFENTRA, the most common adverse reactions occurring in ≥3% of ZYMFENTRA -treated patients included site reactions, COVID-19, anemia, arthralgia, infection site reaction, increased alanine aminotransferase and abdominal pain for UC, and COVID-19, headache, upper respiratory tract infection, injection site reaction, diarrhea, increased blood creatine phosphokinase, arthralgia, increased alanine aminotransferase, hypertension, urinary tract infection, neutropenia, dizziness and leukopenia for CD. Please click for Full U.S. Prescribing Information. Globally, prescribing information varies; refer to the individual country product label for complete information. References Contacts Sarah Amundsen [email protected] +1 920-946-0918 SOURCE Celltrion USA

Clinical ResultDrug Approval

20 May 2024

·www.prnewswire.com

TREMFYA® (guselkumab) QUASAR Maintenance Study in UC met its primary endpoint and all major secondary endpoints, including highly statistically significant rates of endoscopic remission

WASHINGTON, May 20, 2024 /PRNewswire/ -- Johnson & Johnson today announced the first data from the Phase 3 QUASAR Maintenance Study (Abstract #759) that showed 50.0 percent (p<0.001) of patients with moderately to severely active ulcerative colitisa (UC) receiving subcutaneous (SC) TREMFYA® (guselkumab) 200 mg every four weeks (q4w) and 45.2 percent (p<0.001) of patients receiving SC TREMFYA® 100 mg every eight weeks (q8w) achieved the primary endpoint of clinical remissionb at Week 44 compared to placebo (18.9 percent).1 In additional analyses of patients who were in clinical remission, 67 percent and 71 percent, respectively, were also in endoscopic remission at Week 44 (Mayo endoscopic subscore [MES]= 0), indicating they had normal appearance of intestinal mucosa.2 "These data suggest the potential of guselkumab to provide durable, clinical remission and improve important high-bar endpoints such as endoscopic remission to the point of normalization and histologic remission, which represent the kind of progress needed in new treatments for this inflammatory bowel disease," said David T. Rubin, M.D., Chief, Section of Gastroenterology, Hepatology and Nutrition, University of Chicago and lead study investigator.f "The clinical results measured at Week 44 in the QUASAR Maintenance Study suggest that treatment with guselkumab is a promising therapy to help ulcerative colitis patients with challenging symptoms that impact their daily lives." Both TREMFYA® treatment groups also met all nine major secondary endpoints with high statistical significance and clinically meaningful improvements versus placebo. A summary of select secondary endpoints from the 44-week Maintenance Study include:1 The proportion of patients with more than one adverse event (AE) was similar across treatment groups: SC TREMFYA® 200mg q4w, 70.0 percent; SC TREMFYA® 100mg q8w, 64.5 percent; placebo, 68.2 percent.1 The most common AEs in the combined TREMFYA® group compared to placebo were COVID-19 (11.2 percent vs. 14.1 percent), UC (11.2 percent vs. 29.7 percent) and joint pain (6.1 percent vs. 6.8 percent), respectively.1 The safety results were consistent to the safety profile of TREMFYA® in the approved indications of moderate to severe plaque psoriasis (PsO) and active psoriatic arthritis (PsA).1,e "The Phase 3 QUASAR Maintenance Study continues to demonstrate the promise of TREMFYA to unlock potential treatment options for patients living with ulcerative colitis who continue to experience debilitating symptoms despite the availability of treatments today," said David Lee, M.D., Ph.D., Global Therapeutic Area Head, Immunology, Johnson & Johnson. "These findings underscore our commitment to elevate the standard of care in ulcerative colitis and strengthen our resolve to advance inflammatory bowel disease science." These data are among 28 oral and poster presentations that Johnson & Johnson is presenting at Digestive Disease Week 2024, highlighting the company's commitment and leadership in advancing the science of inflammatory bowel disease. This year, Johnson & Johnson submitted regulatory applications seeking the approval of TREMFYA® for the treatment of adults with moderately to severely active UC in countries or regions including the United States and Europe. Editor's Notes: a. Baseline modified score of 5 to 9 with a Mayo rectal bleeding subscore of ≥ 1 and a Mayo endoscopy subscore ≥ 2 based on central review.1 b. Clinical remission was defined as a Mayo stool frequency subscore of 0 or 1 and not increased from induction baseline, a Mayo rectal bleeding subscore of 0, and a Mayo endoscopy subscore of 0 or 1 with no friability present on the endoscopy.1 c. Endoscopic remission (normalization) was defined as a MES of 0.1 d. Histologic-endoscopic mucosal improvement was defined as achieving a combination of histologic improvement (neutrophil infiltration in <5 percent of crypts, no crypt destruction, and no erosions, ulcerations or granulation tissue per Geboes grading system) and endoscopic improvement.1 e. TREMFYA® is not approved for the treatment of adults living with UC in the U.S. f. Dr. Rubin is a paid consultant for Johnson & Johnson. He has not been compensated for any media work. g. Endoscopic improvement was defined as an endoscopy subscore of 0 or 1 with no friability present on the endoscopy.1 h. Clinical response was defined as a decrease from induction baseline in the modified Mayo score by ≥30 percent and ≥2 points, with either a ≥1-point decrease from baseline in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1.1 ABOUT THE QUASAR PROGRAM (NCT04033445) QUASAR is a randomized, double-blind, placebo-controlled, parallel group, multicenter, seamless Phase 2b/3 program designed to evaluate the efficacy and safety of guselkumab, a selective IL-23 inhibitor, in adult patients with moderately to severely active ulcerative colitis who experienced an inadequate response or who demonstrate intolerance to conventional therapy (e.g., thiopurines or corticosteroids), other biologics and/or JAK inhibitors (i.e., tumor necrosis factor [TNF]-alpha antagonists, vedolizumab, or tofacitinib).3 QUASAR includes a Phase 2b dose-ranging induction study, a confirmatory Phase 3 induction study, a Phase 3 randomized withdrawal maintenance study, and a long-term extension study through a total of 5 years. Efficacy, safety, pharmacokinetics, immunogenicity, and biomarkers are assessed at specified time points.2 In the Phase 3 randomized withdrawal QUASAR Maintenance Study, adult patients who demonstrated a clinical response to 12 weeks of TREMFYA® IV induction in the Phase 2 and Phase 3 induction studies were randomized 1:1:1 to three treatment groups: SC TREMFYA® 200 mg q4w, TREMFYA® 100 mg q8w or placebo (TREMFYA® withdrawal).1 The major secondary endpoints included corticosteroid-free clinical remission, maintenance of clinical remission, clinical response, symptomatic remission, endoscopic improvement, histo-endoscopic mucosal improvement, endoscopic normalization, Inflammatory Bowel Disease Questionnaire (IBDQ) remission, and fatigue response at Week 44 (56 weeks after initiation of treatment).1 ABOUT ULCERATIVE COLITIS Ulcerative colitis is a chronic disease of the large intestine, also known as the colon, in which the lining of the colon becomes inflamed and develops tiny open sores, or ulcers, that produce pus and mucus. It is the result of the immune system's overactive response.4 Symptoms vary but may typically include loose and more urgent bowel movements, rectal bleeding or bloody stool, persistent diarrhea, abdominal pain, loss of appetite, weight loss, and fatigue. UC patients also have increased rates of depression.3 ABOUT TREMFYA® (guselkumab) Developed by Johnson & Johnson, TREMFYA® is the first approved fully-human dual-acting monoclonal antibody that blocks IL-23 by binding to the p19 subunit of IL-23 and binding to CD64, a receptor on cells that produce IL-235. IL-23 is an important driver of the pathogenesis of inflammatory diseases.4 Findings for dual acting are limited to in vitro studies that demonstrate guselkumab binds to CD64, which is expressed on the surface of IL-23 producing cells in an inflammatory monocyte model. The clinical significance of this finding is not known.6,7,8,9 TREMFYA® is approved in the U.S. and a number of other countries for the treatment of adults with moderate to severe plaque PsO who are candidates for injections or pills (systemic therapy) or phototherapy (treatment using ultraviolet light) and for the treatment of adult patients with active PsA.4,10 It is also approved in the EU for the treatment of moderate to severe plaque PsO in adults who are candidates for systemic therapy and for the treatment of active PsA in adult patients who have had an inadequate response or who have been intolerant to a prior disease-modifying antirheumatic drug therapy.11 Johnson & Johnson maintains exclusive worldwide marketing rights to TREMFYA®. IMPORTANT SAFETY INFORMATION4 What is the most important information I should know about TREMFYA® (guselkumab)? TREMFYA® is a prescription medicine that may cause serious side effects, including: Serious Allergic Reactions. Stop using TREMFYA® and get emergency medical help right away if you develop any of the following symptoms of a serious allergic reaction: fainting, dizziness, feeling lightheaded (low blood pressure) swelling of your face, eyelids, lips, mouth, tongue, or throat trouble breathing or throat tightness chest tightness skin rash, hives itching Infections. TREMFYA® may lower the ability of your immune system to fight infections and may increase your risk of infections. Your healthcare provider should check you for infections and tuberculosis (TB) before starting treatment with TREMFYA® and may treat you for TB before you begin treatment with TREMFYA® if you have a history of TB or have active TB. Your healthcare provider should watch you closely for signs and symptoms of TB during and after treatment with TREMFYA®. Tell your healthcare provider right away if you have an infection or have symptoms of an infection, including: fever, sweats, or chills muscle aches weight loss cough warm, red, or painful skin or sores on your body different from your psoriasis diarrhea or stomach pain shortness of breath blood in your phlegm (mucus) burning when you urinate or urinating more often than normal Do not use TREMFYA® if you have had a serious allergic reaction to guselkumab or any of the ingredients in TREMFYA®. Before using TREMFYA®, tell your healthcare provider about all of your medical conditions, including if you: have any of the conditions or symptoms listed in the section "What is the most important information I should know about TREMFYA®?" have an infection that does not go away or that keeps coming back. have TB or have been in close contact with someone with TB. have recently received or are scheduled to receive an immunization (vaccine). You should avoid receiving live vaccines during treatment with TREMFYA®. are pregnant or plan to become pregnant. It is not known if TREMFYA® can harm your unborn baby. are breastfeeding or plan to breastfeed. It is not known if TREMFYA® passes into your breast milk. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. What are the possible side effects of TREMFYA®? TREMFYA® may cause serious side effects. See "What is the most important information I should know about TREMFYA®?" The most common side effects of TREMFYA® include: upper respiratory infections, headache, injection site reactions, joint pain (arthralgia), diarrhea, stomach flu (gastroenteritis), fungal skin infections, herpes simplex infections, and bronchitis. These are not all the possible side effects of TREMFYA®. Call your doctor for medical advice about side effects. Use TREMFYA® exactly as your healthcare provider tells you to use it. Please read the full Prescribing Information , including Medication Guide for TREMFYA®, and discuss any questions that you have with your doctor. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit or call 1– 800– FDA– 1088. ABOUT JOHNSON & JOHNSON At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity. Learn more at or at . Follow us at @JNJInnovMed. Janssen Research & Development, LLC and Janssen Biotech, Inc. are Johnson & Johnson companies. Cautions Concerning Forward-Looking Statements This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding TREMFYA®. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Research & Development, LLC, Janssen Biotech, Inc. and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended December 31, 2023, including in the sections captioned "Cautionary Note Regarding Forward-Looking Statements" and "Item 1A. Risk Factors," and in Johnson & Johnson's subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at , or on request from Johnson & Johnson. None of Janssen Research & Development, LLC, Janssen Biotech, Inc. nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments. SOURCE Johnson & Johnson

Clinical ResultDrug ApprovalPhase 3Phase 2

100 Deals associated with Mercaptopurine

External Link

KEGG	Wiki	ATC	Drug Bank
D00161	Mercaptopurine	L01BB02	DB01033

R&D Status

Approved

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Choriocarcinoma	CN	Changzhou Yabang Pharmaceutical Co., Ltd.	01 Jan 1992
Choriocarcinoma	CN	Shanxi Xingbang Pharmaceutical Co. Ltd.	01 Jan 1992
Leukemia	JP	Ohara Pharmaceutical Co., Ltd.	26 Dec 1956
Philadelphia chromosome positive chronic myelogenous leukemia	JP	Ohara Pharmaceutical Co., Ltd.	26 Dec 1956
Acute Lymphoblastic Leukemia	US	Stason Industrial Corp.	11 Sep 1953
Acute Myelomonocytic Leukemia	US	Stason Industrial Corp.	11 Sep 1953
Central Nervous System Neoplasms	US	Stason Industrial Corp.	11 Sep 1953

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Hydatidiform Mole	NDA/BLA	CN	China Resources Double-Crane Pharmaceutical Co., Ltd.	29 Sep 2023
Crohn Disease	Phase 2	IL	Teva Pharmaceutical Industries Ltd.	01 Nov 2010

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02553460 (CTgov)	Phase 1/2	Acute Lymphoblastic Leukemia	50	glucocorticoids+hydroxyurea+vincristine	iitwirnbkc(tcsedcghbb) = ffxobiiaul jicvkqsqbs (hyiuwzvlba, cnfqxvgdxe - grdohsmrxj) View more	-	07 Jun 2023
NCT02101853 (AALL1331, CTgov)	Phase 3	Recurrent B Acute Lymphoblastic Leukemia \| Pre B-cell acute lymphoblastic leukemia	669	Asparaginase+etoposide+CYCLOPHOSPHAMIDE+Leucovorin Calcium+pegaspargase+Therapeutic Hydrocortisone+Mitoxantrone+Dexamethasone+Vincristine Sulfate+Methotrexate+Cytarabine (Arm A (HR and IR Control))	trmpylgndy(osbomdlvbw) = wykvmtziqk ogsarraofl (jdactbaagi, dmarecvoeq - obyeiybgcc) View more	-	06 Dec 2022
NCT02101853 (AALL1331, CTgov)	Phase 3		669	Pharmacological Study+Therapeutic Hydrocortisone+blinatumomab+Dexamethasone+Methotrexate+Cytarabine (Arm B (HR and IR Blinatumomab))	trmpylgndy(osbomdlvbw) = hcphosxhht ogsarraofl (jdactbaagi, uzdrqkxmew - zbmsxiiwbw) View more	-	06 Dec 2022
NCT03518112 (CTgov)	Phase 2	Recurrent B Acute Lymphoblastic Leukemia \| Philadelphia Chromosome Negative Acute Lymphoblastic Leukemia \| Refractory B Acute Lymphoblastic Leukemia	6	Laboratory Biomarker Analysis+cyclophosphamide+Leucovorin Calcium+Filgrastim+Mercaptopurine+blinatumomab+Dexamethasone+Rituximab+Vincristine Sulfate+Methotrexate+Cytarabine	vulolasqep(ftibevpvcg) = bspnligpbg ksiniqbwzm (ipdfwtvvsg, aajpmqjpmt - ffjcvdeuhv) View more	-	04 Nov 2022
NCT02828358 (AALL15P1, CTgov)	Phase 2	Pre B-cell acute lymphoblastic leukemia \| Mixed phenotype acute leukemia	78	HC+cyclophosphamide+PEG+leucovorin calcium+thioguanine+6-MP+dexamethasone+MTX+vincristine sulfate+daunorubicin hydrochloride+ARA-C (KMT2A-Rearranged)	zrviijchjk(vpzadodbnx) = ptqrgkgovs ndahzlwgam (xxckcszcqn, luqaowgkeu - qgmthklqlt) View more	-	26 Oct 2021
NCT02828358 (AALL15P1, CTgov)	Phase 2		78	cytarabine (ARA-C)+prednisolone+dexamethasone+vincristine sulfate+Methotrexate+daunorubicin hydrochloride (KMT2A-Germline)	gvciqrjkut(cftqfpslhx) = wnsborzmid ozilmqaqez (trnhjawdxp, aukpnyayic - jzllqcelos) View more	-	26 Oct 2021
NCT03488225 (CTgov)	Phase 2	Chronic Lymphocytic Leukemia \| Philadelphia Chromosome Negative Acute Lymphoblastic Leukemia \| Pre B-cell acute lymphoblastic leukemia	4	Laboratory Biomarker Analysis+doxorubicin hydrochloride+Inotuzumab Ozogamicin+Mercaptopurine+Methotrexate+Cytarabine+CYCLOPHOSPHAMIDE+Leucovorin Calcium+prednisone+Dexamethasone+Rituximab+Vincristine Sulfate+ofatumumab	gsisjdhijl(mhgvfdmbvo) = beutekmxzj dercbrffch (qzswxiewvw, dzrragxiid - pvxsemdwwm) View more	-	13 Apr 2021
NCT01503632 (Pubmed)	Phase 3	Acute Lymphoblastic Leukemia	444	Mercaptopurine (Education alone)	nwdcprzdia(ehnczxvksv) = rgyccddtzm phcjeikcpb (akgbtepwpn )	-	03 Aug 2020
NCT01503632 (Pubmed)	Phase 3	Acute Lymphoblastic Leukemia	444	Mercaptopurine (Intervention package)	nwdcprzdia(ehnczxvksv) = bcsqjvicxe phcjeikcpb (akgbtepwpn )	-	03 Aug 2020
NCT01906671 (Pubmed \| Cancer Chemother Pharmacol)	Phase 4	Acute Lymphoblastic Leukemia	16	6MP tablet (Puri-Nethol®)	mxcbejhaic(rzhjkpturu) = bcnrjwkojh iqebmswzxf (tqbrnzkjgf )	-	01 Jul 2020
NCT01906671 (Pubmed \| Cancer Chemother Pharmacol)	Phase 4	Acute Lymphoblastic Leukemia	16	6MP liquid suspension (Xaluprine®)	mxcbejhaic(rzhjkpturu) = udxruojbmv iqebmswzxf (tqbrnzkjgf )	-	01 Jul 2020
NCT01432145 (Pubmed)	Phase 2	Neoplasms	67	6-mercaptopurine (6MP)	gtravjoetu(xhpcdbbczs) = gxdcutblun urxiupivmm (gcrsmnlsbg ) View more	-	01 Feb 2020
NCT02413047 (CTgov)	Not Applicable	Crohn Disease \| Colitis, Ulcerative	3	Azathioprine+6 mercaptopurine+Methotrexate	ovlauqomhs(wqplekookz) = ndzifhjetv ocdrllezor (ubthkcmjiz, fgmhucdjsp - dchymrlqqp) View more	-	04 Nov 2019
NCT00866749 (CTgov)	Phase 2	Acute Lymphoblastic Leukemia	120	PEG-asparaginase+Cyclophosphamide+doxorubicin+Thioguanine+Mercaptopurine+Methotrexate+Vincristine+cytarabine+Daunorubicin	maiquqtuku(vvtpgemmtg) = fthvgelptc wwchuwektf (npwukwwumz, sraiwtchhf - rentxlzqff) View more	-	10 Sep 2019

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Leverages most recent intelligence information, enabling fullest potential.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis