RegulationPriority Review (United States), Breakthrough Therapy (United States), Orphan Drug (United States), Orphan Drug (European Union), Orphan Drug (Australia), Orphan Drug (United Kingdom)

Structure/Sequence

Sequence Code 315603822L

Source: *****

Sequence Code 315603823H

Source: *****

Clinical Trials associated with Crizanlizumab-TMCA

NCT06439082

/ RecruitingPhase 3

A Phase III, Multicenter, Randomized, Placebo Controlled, Double-blind Study to Assess Efficacy and Safety of Crizanlizumab (5 mg/kg) Versus Placebo, With or Without Hydroxyurea/Hydroxycarbamide Therapy, in Adolescent and Adult Sickle Cell Disease Patients With Frequent Vaso-Occlusive Crises

A phase III, multi-center, randomized, placebo-controlled, double-blind study to assess efficacy and safety of crizanlizumab (5 mg/kg) versus placebo, with or without hydroxyurea/hydroxycarbamide therapy, in adolescent and adult Sickle Cell Disease patients with frequent vaso-occlusive crises.

Start Date24 Oct 2024

Sponsor / Collaborator

Novartis Pharmaceuticals Canada, Inc.

NCT05469828

/ Not yet recruitingPhase 1/2IIT

Crizanlizumab Improves Tissue Oxygen Supply Demand Matching in Patients With Sickle Cell Anemia

Hypothesis
Efficient unloading of oxygen to regions of high metabolic demand requires a healthy microvasculature to sense local oxygen tension and regulate flow, accordingly. In sickle cell disease patients, the investigators have demonstrated oxygen supply-demand mismatch, or SDM, in proportion to anemia severity. SDM occurs in both the peripheral circulation and the brain, and four characteristics: 1) Hyperemia beyond expected for the level of anemia, 2) Corresponding loss of vascular dilatory reserve, 3) Impaired oxygen unloading to the tissues, and 4) Tissue hypoxia. In sickle cell disease, red blood cell (RBC) and white blood cell (WBC) adhere to vascular endothelium triggering transient or irreversible microvascular damage as well as releasing vasoactive substances that contribute to microvascular dysregulation. The investigators postulate that ongoing microvascular damage/dysregulation in the setting of increased total blood flow contributes to SDM. The investigators believe SEG101, by lowering RBC and WBC adhesion to the microvasculature, will improve SDM and tissue oxygenation.
Objectives
Primary - The investigators will test whether SEG101 improves SDM in patients with sickle cell anemia by measuring the change in tissue oxygenation measured by near infrared spectroscopy (NIRS).
Secondary/Exploratory - The investigators will identify end-organ disease and whether improvement of SDM by SEG101 occurs in patients with sickle cell anemia.

Start Date01 Jul 2024

Sponsor / Collaborator

Children's Hospital Los Angeles

[+1]

NCT05909618

/ RecruitingPhase 2IIT

An Open Label Phase 2 Study of Intravenously Administered Crizanlizumab Alone or in Combination With Nivolumab for Glioblastoma and Melanoma With Brain Metastases

A single-center, open-label, non-randomized phase I/II study to evaluate the efficacy, safety and tolerance of crizanlizumab monotherapy and in combination with nivolumab in patients with advanced glioblastoma (GB) who exhausted standard of care (SOC) therapy, patients with metastatic brain melanoma (MBM) and patients with newly diagnosed unmethylated GB.
Subjects will be screened for up to 28 days prior to treatment initiation. Eligible subjects will be allocated to one of 3 cohorts:
Cohort 1: Patients with metastatic melanoma with primarily diagnosed or newly progressing brain metastases who failed immunotherapy.
Cohort 2: Patients with recurrent or progressing GB following primary radiation therapy and temozolomide. Patients may have failed up to 2 prior systemic treatment lines (including temozolomide as adjuvant therapy) and are candidates for further treatment.
Cohort 3: Patients with newly diagnosed GB who were evaluated for methylguanine-DNA methyltransferase(MGMT) methylation status and have un-methylated MGMT promotor-therefore, they are not candidates for maintenance temozolomide therapy.

Start Date11 Jul 2023

Sponsor / Collaborator

Sheba Medical Center

100 Clinical Results associated with Crizanlizumab-TMCA

100 Translational Medicine associated with Crizanlizumab-TMCA

100 Patents (Medical) associated with Crizanlizumab-TMCA

122

Literatures (Medical) associated with Crizanlizumab-TMCA

01 Jul 2026·Cancer research communications

Tumor-Associated Platelets Suppress T-cell Function and Promote Immune Evasion in TNBC via the P-selectin/P-selectin Glycoprotein Ligand 1 Pathway

Article

Author: Kane, Natalie ; Gautam, Deepa ; Davenport, Patricia ; Goggi, Giovanni ; Battinelli, Elisabeth M. ; Sullivan, Megan E. ; Baginska, Joanna ; Garrido-Castro, Ana C. ; Brown, Jared ; Petrarca, Grace C. ; McAllister, Sandra S. ; Roweth, Harvey G. ; Spasic, Milos ; Smith-Oliver, Margaret R. ; Clarke, Emily M.

Abstract:

Tumor-associated platelets (TAP), which are reprogrammed by tumor-derived signals to acquire immunosuppressive properties, represent an emerging mechanism of immune evasion in triple-negative breast cancer (TNBC). Although immune checkpoint inhibitors have shown promise, their efficacy is frequently limited by T-cell exhaustion and therapeutic resistance. In this study, we demonstrate that TAPs, unlike healthy circulating platelets, induce T-cell dysfunction through platelet-derived P-selectin, which engages P-selectin glycoprotein ligand 1 (PSGL-1) on T cells. This interaction promotes immunosuppressive signaling, driving T-cell exhaustion and impairing antitumor cytotoxicity. Using in vitro coculture systems and in vivo TNBC models, we show that disruption of the P-selectin–PSGL-1 axis, including pharmacologic blockade with the FDA-approved anti–P-selectin antibody crizanlizumab, restores T-cell function and enhances responsiveness to immune checkpoint blockade. Notably, PSGL-1, traditionally recognized for its role in leukocyte trafficking and immune regulation, is co-opted by TAPs to suppress T-cell activity, revealing a mechanism of platelet-mediated immune modulation. These findings establish TAPs as active regulators of antitumor immunity and identify the P-selectin–PSGL-1 axis as a therapeutically actionable target to overcome resistance to immunotherapy in TNBC.

Significance::

Tumor-associated platelets help TNBCs evade immune attack by suppressing T-cell function through P-selectin signaling. Blocking this pathway with crizanlizumab restores antitumor immunity and enhances response to immunotherapy, identifying a promising new combination treatment strategy for patients with this aggressive form of breast cancer.

01 Apr 2026·AMERICAN JOURNAL OF HEMATOLOGY

Advancing Sickle Cell Disease Treatment in Sub‐Saharan Africa: Challenges and Opportunities for Disease Modifying Therapies

Review

Author: Ambrose, Emmanuela E. ; Power‐Hays, Alexandra ; Dei‐Adomakoh, Yvonne

ABSTRACT:

Sickle cell disease (SCD) is a major individual and public health challenge in sub‐Saharan Africa, where over 5 million affected individuals live and where access to disease‐modifying treatment is limited. Despite established safety and efficacy of hydroxyurea, its use is limited across the region due to inconsistent healthcare infrastructure, high medication and laboratory costs, inadequate clinician training, and persistent disease stigma. Practical hydroxyurea dosing strategies, integration into national health plans, and a stronger supply chain are necessary to improve access to this life‐saving medication. Newly approved medications, such as L‐glutamine and crizanlizumab, may provide additional benefits to select patients, but are expensive and unavailable. The increased mortality observed in people on voxelotor in Africa highlights the need to ensure the safety of any new medication in varied settings through high‐quality research conducted on the continent. Overall, holistic strategies are needed to improve SCD care in Africa, such as universal screening with connection to comprehensive care that includes disease‐modifying treatment, community and healthcare worker education, centers of excellence, and capacity building. SCD management in Africa can be transformed by addressing systemic barriers and leveraging collaborative partnerships, leading to reduced mortality and alleviation of the individual and economic burdens of the disease. It is a moral and economic imperative to prioritize access to SCD treatment in Africa, the region with the greatest disease burden globally.

10 Feb 2026·Blood Advances

Low bone mineral density and pain impact in adults with sickle cell disease

Article

Author: Wun, Ted ; Wu, Qian V. ; Adesina, Oyebimpe O. ; Zemel, Babette ; Nalbant, Hande ; Nardo, Lorenzo ; Voutsinas, Jenna ; Rokni, Mehrad ; Teos, Leyla Y.

Abstract:

Low bone mineral density (BMD) is a prevalent skeletal finding in sickle cell disease (SCD), but its clinical consequences are poorly understood. We hypothesized that low BMD, independent of osteonecrosis (ON), would associate with pain in adults with SCD. In the SCD Bone Pain study, 53 ambulatory adults (64% females; mean age, 38 ± 11 years; 66% hemoglobin [Hb] SS/Sβ0 thalassemia) underwent dual-energy X-ray absorptiometry scans of their lumbar spine, hip, forearm, and whole body. They also completed the Adult Sickle Cell Quality of Life Measurement Information System pain impact questionnaire. Twenty-three participants (43%) had low BMD, defined as lumbar spine, total hip, or femoral neck BMD z scores of −2 or less. In multivariate linear regression, lumbar spine BMD z scores significantly changed by +0.31, −0.29, −0.14, and −1.3 for every unit increase in Hb, indirect bilirubin, and white blood cell count, and with crizanlizumab use, respectively. Pain impact T-scores significantly decreased (worsened) by 6.0 and 6.5 with reduced estimated glomerular filtration rate and chronic opioid therapy but increased (improved) by 3.8 for every unit increase in serum phosphate. The median [interquartile range] pain impact T-scores were significantly lower in participants with low BMD and ON (38.3 [37.4, 40.1]) than those with either low BMD (49.5 [43.6, 54.4]; P = 3 × 10−5) or ON (52.7 [45.3, 57]; P = 2 × 10−4) alone. Whether sickle cell–related low BMD results from impaired bone formation and/or accelerated bone loss remains unclear. Understanding how low bone density, with or without ON, mediates SCD pain warrants further investigation. This trial was registered at www.clinicaltrials.gov as #NCT05283148.

News (Medical) associated with Crizanlizumab-TMCA

31 Jul 2026

·www.biopharmadive.com

Agios scraps sickle cell drug

Dive Brief:Agios Pharmaceuticals has decided not to further develop one of its more closely watched medicines as a treatment for sickle cell disease due to disappointing results from a mid-stage clinical trial.The drug, called tebapivat, did not demonstrate the level of differentiation required to support continued development, Agios said in a statement. Tebapivat has been billed as a next-generation version of another Agios medicine, mitapivat, which is already approved for use in two blood disorders. These drugs work by activating the pyruvate kinase enzyme thats essential for the health and survival of red blood cells.Shares of Agios were down 6.5%, to about $37.50 apiece, in mid-morning trading Tuesday. Leerink Partners analyst Andrew Berens wrote in a note to clients that, while his team had not yet attributed any of Agios stock value to tebapivat, the drug did represent the companys primary opportunity to differentiate itself in sickle cell disease from Novo Nordisk, which has its own once-daily enzyme activator that recently scored positive Phase 3 results.Dive Insight:Tebapivat is the latest example that drug companies, whether in research or in selling a product, find sickle cell significantly challenging.Just last month, Fulcrum Therapeutics, a Boston-area biotechnology firm, said it made the very difficult decision to stop advancing a potential sickle cell medicine because the Food and Drug Administration had unshakable concerns about safety risks. That medicine, pociredir, had already gone through early-stage human testing. But with no viable regulatory path forward for Fulcrums main asset, the company is now looking into strategic alternatives, including a possible sale.The Fulcrum update came less than a year after Pfizer unveiled underwhelming resultsfor a sickle cell drug it had picked up through the $5.4 billion acquisition Global Blood Therapeutics. In 2024, the pharmaceutical giant pulled a central asset in that deal, Oxbryta, from the market because of safety concerns. Novartis, too, withdrew a sickle cell therapy named Adakveo from the European market after regulators formally revoked the drugs authorization.Elsewhere, Sangamo Therapeutics and Graphite Bio each discontinued development of an experimental genetic medicine in 2023.Agios had another recent setback, disclosing in November mixed results from a late-stage trial evaluating mitapivat against sickle cell. The company is still forging ahead on that front, though, and expects an FDA approval decision by Nov. 1.In his client note, Berens wrote that tebapivats end places greater importance on the commercial execution of mitapivat and a smooth FDA review of the drugs expansion into sickle cell. It also puts more pressure on the company to succeed with its earlier-stage research projects and to take advantage of potential business development opportunities, the analyst added. '

Phase 3AcquisitionDrug ApprovalClinical ResultCell Therapy

02 Jul 2026

·www.biospace.com

Vertex Announces US FDA Approval for Expanded Use of CASGEVY® for the Treatment of People Ages 2 Years and Older With Sickle Cell Disease or Transfusion-Dependent Beta Thalassemia

- First and only approved genetic therapy to treat children as young as 2 years for both severe sickle cell disease and transfusion-dependent beta thalassemia - - Approximately 5,500 additional children in the U.S. are now eligible for this established one-time therapy, expanding upon the prior FDA approval in people 12 years and older - - Regulatory review for label expansion underway in the Kingdom of Saudi Arabia and United Kingdom - BOSTON--(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) announced today that the U.S. Food and Drug Administration (FDA) has approved expanded use of CASGEVY ® (exagamglogene autotemcel) for the treatment of people ages 2 years and older with either sickle cell disease (SCD) with recurrent vaso-occlusive crises (VOCs) or transfusion-dependent beta thalassemia (TDT). CASGEVY is the first approved genetic therapy indicated for children as young as 2 years for both SCD and TDT. “Just as we redefined what is possible in cystic fibrosis, our ambition is to transform the future for people living with sickle cell disease and transfusion-dependent beta thalassemia. The remarkable consistency of results across age groups reinforces the potential of CASGEVY to deliver durable, transformative benefits to those who have historically had limited options,” said Reshma Kewalramani, M.D., Chief Executive Officer and President, Vertex. “We’re deeply grateful to the patients, families and investigators who participated in the clinical trials that led to this historic approval, and we are ready to bring CASGEVY to children and their families across the U.S.” “Today’s approval offers renewed hope for children living with sickle cell disease or transfusion‑dependent beta thalassemia,” said Haydar Frangoul, M.D., M.S., Medical Director of HCA Healthcare’s Sarah Cannon Transplant and Cellular Therapy Program at TriStar Centennial Children’s Hospital, investigator with Sarah Cannon Research Institute (SCRI) and Member of Vertex’s SCD Program Steering Committee. “Earlier access to the transformative potential of this therapy will allow clinicians and families to consider treatment before years of cumulative damage from these life-shortening diseases take hold.” Vertex has established a network of independently operated, authorized treatment centers (ATCs) throughout the U.S. to offer CASGEVY to eligible patients through existing access and reimbursement pathways. Today, there are more than 75 activated ATCs in the U.S. The full list can be accessed at CASGEVY.com . About Sickle Cell Disease (SCD) Sickle cell disease (SCD) is a rare serious, inherited blood disease that is progressive and life‑shortening. The disease causes red blood cells to become rigid and misshapen, restricting blood flow and oxygen delivery to vital organs. Recurrent vaso‑occlusive crises (VOCs), unpredictable episodes of severe pain caused by blocked blood vessels, are a defining feature of SCD and frequently require hospitalization. Many patients experience these complications early in life, and over time, repeated VOCs and chronic anemia lead to progressive and irreversible organ damage, including damage to the brain, lungs, kidneys and heart. SCD places a substantial burden on patients and their families, who must manage frequent medical visits, hospitalizations, school and work disruptions, and the emotional toll of chronic pain and life‑threatening complications. Despite lifelong treatment, people with SCD and recurrent VOCs in the U.S. face shortened life expectancy, with a median age of death of approximately 45 years, report quality‑of‑life scores far below the general population and the estimated lifetime healthcare costs of managing the disease are $4–6 million. About Transfusion‑Dependent Beta Thalassemia (TDT) Transfusion‑dependent beta thalassemia (TDT) is a rare serious, inherited blood disease that is progressive and life‑shortening. The disease impairs the body’s ability to produce sufficient hemoglobin, limiting oxygen delivery to tissues and organs. People with TDT do not have enough functional hemoglobin in their red blood cells and require regular, lifelong blood transfusions, often beginning early in childhood, along with ongoing iron chelation therapy. While transfusions are necessary for survival, many of the long‑term complications of TDT are exacerbated by chronic transfusion therapy and iron overload and cumulative damage to the heart, liver and endocrine system, as well as bone abnormalities and delayed growth and puberty. TDT places a significant and ongoing burden on patients and their families, requiring frequent medical visits and complex lifelong treatment. Despite lifelong treatment, people with TDT in the U.S. face shortened life expectancy, with a median age of death of approximately 37 years, reduced quality of life and productivity, and the estimated lifetime healthcare costs of managing the disease are $5–5.7 million. About CASGEVY ® (exagamglogene autotemcel) CASGEVY is a non-viral, ex vivo CRISPR/Cas9 gene-edited cell therapy for eligible patients with SCD or TDT, in which a patient’s own hematopoietic stem and progenitor cells are edited at the erythroid specific enhancer region of the BCL11A gene through a precise double-strand break. This edit results in the production of high levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells. HbF is the form of the oxygen-carrying hemoglobin that is naturally present during fetal development, which then switches to the adult form of hemoglobin after birth. CASGEVY has been shown in clinical trials to reduce or eliminate VOCs for patients with SCD and transfusion requirements for patients with TDT. In the United States, CASGEVY was approved using the Commissioner’s National Priority Voucher. Vertex has also recently completed regulatory submissions in the Kingdom of Saudi Arabia and United Kingdom to expand the use of CASGEVY to children as young as five. About the CLIMB Studies The completed Phase 1/2/3 open-label studies, CLIMB-111 and CLIMB-121, were designed to assess the safety and efficacy of a single dose of CASGEVY in patients ages 12-35 years with TDT or with SCD and recurrent VOCs. Patients were followed for approximately two years after CASGEVY infusion in these studies. CLIMB-141 and CLIMB-151 are ongoing Phase 3 open-label studies, designed to assess the safety and efficacy of a single dose of exagamglogene autotemcel in patients ages 2-11 years with TDT or with SCD and recurrent VOCs. Enrollment and dosing are complete for the 5–11-year-old cohort in both studies. Each patient in these studies is asked to participate in the ongoing long-term, open-label study, CLIMB-131. CLIMB-131 is designed to evaluate the long-term safety and efficacy of CASGEVY in patients with up to 15 years of follow up after CASGEVY infusion. U.S. INDICATIONS AND IMPORTANT SAFETY INFORMATION FOR CASGEVY INDICATION CASGEVY is indicated for the treatment of patients aged 2 years and older with: sickle cell disease (SCD) with recurrent vaso-occlusive crises (VOCs) transfusion-dependent β-thalassemia (TDT) IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS Neutrophil Engraftment Failure There is potential risk of neutrophil engraftment failure after treatment with CASGEVY. In the clinical trials, all treated patients achieved neutrophil engraftment and no patients received rescue CD34 + cells. Monitor absolute neutrophil counts (ANC) and manage infections according to standard guidelines and medical judgement. In the event of neutrophil engraftment failure, patients should be infused with rescue CD34 + cells. Granulocyte colony-stimulating factor (G-CSF) is not recommended for 21 days after CASGEVY infusion. Delayed Platelet Engraftment Delayed platelet engraftment has been observed with CASGEVY treatment. There is an increased risk of bleeding until platelet engraftment is achieved. Monitor patients for bleeding according to standard guidelines and medical judgement. Conduct frequent platelet counts until platelet engraftment and platelet recovery are achieved. Perform blood cell count determination and other appropriate testing whenever clinical symptoms suggestive of bleeding arise. Hypersensitivity Reactions Hypersensitivity reactions, including anaphylaxis can occur due to dimethyl sulfoxide (DMSO) or dextran 40 in the cryopreservation solution. Monitor patients for hypersensitivity reactions during and after infusion. Off-Target Genome Editing Risk The risk of unintended, off-target editing in an individual’s CD34 + cells cannot be ruled out due to genetic variants. The clinical significance of potential off-target editing is unknown. ADVERSE REACTIONS The most common Grade 3 or 4 non‑laboratory adverse reactions (occurring in ≥ 25%) were mucositis and febrile neutropenia in patients with SCD and patients with TDT, and decreased appetite in patients with SCD. All (100%) of the patients with TDT and SCD experienced Grade 3 or 4 neutropenia and thrombocytopenia. Other common Grade 3 or 4 laboratory abnormalities (≥ 50%) include leukopenia, anemia, and lymphopenia. DRUG INTERACTIONS No formal drug interaction studies have been performed. CASGEVY is not expected to interact with the hepatic cytochrome P450 family of enzymes or drug transporters. Use of Granulocyte-Colony Stimulating Factor (G-CSF): G-CSF must not be used for CD34 + HSC mobilization of patients with SCD. Use of Hydroxyurea: Discontinue the use of hydroxyurea at least 8 weeks prior to start of each mobilization cycle and conditioning. There is no experience of the use of hydroxyurea after CASGEVY infusion. Use of Crizanlizumab: Discontinue the use of crizanlizumab at least 8 weeks prior to start of mobilization and conditioning, as their interaction potential with mobilization and myeloablative conditioning agents is not known. Use of Iron Chelators: Discontinue the use of iron chelators at least 7 days prior to initiation of myeloablative conditioning, due to potential interaction with the conditioning agent. Some iron chelators are myelosuppressive. If iron chelation is required, avoid the use of non-myelosuppressive iron chelators for at least 3 months and use of myelosuppressive iron chelators for at least 6 months after CASGEVY infusion. Phlebotomy can be used instead of iron chelation, when appropriate. USE IN SPECIFIC POPULATIONS Pregnancy/Lactation: CASGEVY must not be administered during pregnancy and breastfeeding should be discontinued during conditioning because of the risks associated with myeloablative conditioning. Pregnancy and breastfeeding after CASGEVY infusion should be discussed with the treating physician. Females and Males of Reproductive Potential: A negative serum pregnancy test must be confirmed prior to the start of each mobilization cycle and reconfirmed prior to myeloablative conditioning. Women of childbearing potential and men capable of fathering a child should use effective methods of contraception from start of mobilization through at least 6 months after administration of CASGEVY. Advise patients of the risks associated with conditioning agents. Infertility has been observed with myeloablative conditioning, therefore, advise patients of fertility preservation options before treatment, if appropriate. Please see full Prescribing Information for CASGEVY. About Vertex Vertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious diseases and conditions. The company has approved therapies for cystic fibrosis, sickle cell disease, transfusion-dependent beta thalassemia and acute pain, and it continues to advance clinical and research programs in these areas. Vertex also has a robust clinical pipeline of investigational therapies across a range of modalities in other serious diseases where it has deep insight into causal human biology, including IgA nephropathy, neuropathic pain, APOL1-mediated kidney disease, primary membranous nephropathy, autosomal dominant polycystic kidney disease, type 1 diabetes, generalized myasthenia gravis, and myotonic dystrophy type 1. Vertex was founded in 1989 and has its global headquarters in Boston, with international headquarters in London. Additionally, the company has research and development sites and commercial offices in North America, Europe, Australia, Latin America and the Middle East. Vertex is consistently recognized as one of the industry's top places to work, including 16 consecutive years on Science magazine's Top Employers list and one of Fortune’s 100 Best Companies to Work For. For company updates and to learn more about Vertex's history of innovation, visit or follow us on LinkedIn , Facebook , Instagram , YouTube and X . Special Note Regarding Forward-Looking Statements This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including, without limitation, statements made by Reshma Kewalramani, M.D., and Haydar Frangoul, M.D., M.S., in this press release, statements regarding the expected clinical benefits of CASGEVY, expectations regarding the eligible patient population, and expectations for patient access to CASGEVY. While Vertex believes the forward-looking statements contained in this press release are accurate, these forward-looking statements represent the company's beliefs only as of the date of this press release and there are a number of factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include the risks listed under the heading “Risk Factors” in Vertex's annual report and in subsequent filings filed with the Securities and Exchange Commission at and available through the company's website at . You should not place undue reliance on these statements. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available. (VRTX-GEN) Contacts Vertex Pharmaceuticals Incorporated Investors: InvestorInfo@vrtx.com or +1 617-341-6108 Media: mediainfo@vrtx.com or 617-341-6992

02 Jun 2026

·www.biopharmadive.com

Fulcrum exploring a potential sale after FDA sidelined its sickle cell drug

Fulcrum Therapeutics has begun a strategic review that may result in it getting sold, a move made after the companys main medicine hit a possibly insurmountable obstacle.On Tuesday, Fulcrum disclosed that, late last month, it received the official record from a recent meeting with the Food and Drug Administration. The meeting revolved around next steps for pociredir, an experimental treatment for sickle cell disease that Fulcrum had ushered through early-stage human testing.According to the company, FDA staff were worried about pociredirs safety, given emerging data that showed higher-than-expected rates of secondary blood cancers in patients who had received an Ipsen drug, Tazverik, which was pulled from the market in March. Fulcrums drug works in a similar-but-different way, and the company tried to make the case that these differences are important to assessing overall benefits and risks. The FDA, though, still concluded the potential hazards were too great and left no viable regulatory path forward.Fulcrum has therefore made the very difficult decision to discontinue development of pociredir, said CEO Alex Sapir. The company is now exploring strategic alternatives, including potentially merging or selling either assets or the entire business. Its also started efforts to significantly reduce operating expenses and preserve capital, though specific details werent provided. Fulcrum had a third of a billion dollars in cash, cash equivalents, and marketable securities as of March 31.Fulcrums stock price, which had already fallen significantly since late last year, cratered following Tuesdays update. Shares were down more than 50%, to just above $3 apiece.With limited visibility into future value creation beyond strategic alternatives and cost-cutting initiatives, we are moving to the sidelines, wrote Leerink Partners analyst Joseph Schwartz, who also downgraded his rating on Fulcrums stock to Market Perform.Schwartz noted, however, that his team was surprised by this outcome due to the effects pociredir demonstrated in that early-stage study. There, the drug boosted fetal hemoglobin levels one of the most proven methods for treating sickle cell and improved red blood cell health in adults with severe disease. Schwartz highlighted how the trial also hadnt reported any new clinical safety signals.Pociredir is designed to inhibit a large protein complex, PRC2, that helps turn off fetal hemoglobin production. It does this by latching onto a specific piece of the protein that, notably, is distinct from where Tazverik binds. Recent clinical data pointing to an increased incidence of hematologic malignancies among patients given Tazverik appears to have led the FDA to draw a hard line regarding the risk/benefit profile of all PRC2 inhibitors regardless of mechanistic differences, Schwartz wrote.The FDA previously put a so-called full clinical hold on Fulcrums program in early 2023, in part because of concerns with the wider class of PRC2-targeting drugs. The hold was lifted that summer, with Fulcrum agreeing to tailor the type of patients who were eligible to participate in its Phase 1 study. Schwartz argues the FDA position regarding pociredir seems to have been biased by malignancy observations seen in preclinical testing.Luca Issi, an analyst at RBC Capital Markets, claims his team wasnt entirely surprised by this outcome. While its unfortunate for the many [sickle cell] patients looking for therapeutic alternatives, we do believe that discontinuing the program is the right pragmatic decision given the FDA clearly believes that this is a class effect, Issi wrote in his own note to clients.Fulcrums is the latest in a string of setbacks for sickle cell drugmakers. In 2023, development was discontinued for three experimental treatments from Intellia Therapeutics, Sangamo Therapeutics and Graphite Bio. Two years later, Pfizer and Agios Pharmaceuticalseach delivered disappointing clinical results.Pfizers study was for a drug that the pharmaceutical giant picked up through the $5.4 billion acquisition of Global Blood Therapeutics. In 2024, Pfizer removed from the market another asset from that deal, the approved sickle cell therapy Oxbryta, because of safety concerns.The year prior, Novartis withdrew Adakveo from the European market after authorities there formally revoked the sickle cell disease drugs authorization.The World Health Organization estimates that, as of 2021, close to 8 million people had sickle cell. The disease causes “vaso-occlusive crises,“ a sudden, brutal wave of pain brought on by the crescent-shaped blood cells block small blood vessels. It can also make patients more vulnerable to infections and trigger chronic damage. Often, the life expectancy for people with sickle is 20 or so years less than their peers. '

Cell TherapyAcquisitionPhase 1Accelerated Approval

100 Deals associated with Crizanlizumab-TMCA

External Link

KEGG	Wiki	ATC	Drug Bank
D11480	Crizanlizumab-TMCA	B06AX01	DB15271

R&D Status

Approved

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Anemia, Sickle Cell	United States	Novartis Pharmaceuticals Corp.	15 Nov 2019
Vaso-occlusive crisis	United States	Novartis Pharmaceuticals Corp.	15 Nov 2019

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Sickle Cell Trait	Phase 3	Netherlands	Novartis Pharma AG	03 May 2021
COVID-19	Phase 2	United States	Novartis AG	09 Jul 2020
Priapism	Phase 2	United States	Novartis Pharmaceuticals Corp.	16 Oct 2019
Myelofibrosis	Phase 2	Australia	Novartis Pharmaceuticals Corp.	26 Sep 2019
Myelofibrosis	Phase 2	Canada	Novartis Pharmaceuticals Corp.	26 Sep 2019
Myelofibrosis	Phase 2	Denmark	Novartis Pharmaceuticals Corp.	26 Sep 2019
Myelofibrosis	Phase 2	Germany	Novartis Pharmaceuticals Corp.	26 Sep 2019
Myelofibrosis	Phase 2	Hungary	Novartis Pharmaceuticals Corp.	26 Sep 2019
Myelofibrosis	Phase 2	Italy	Novartis Pharmaceuticals Corp.	26 Sep 2019
Myelofibrosis	Phase 2	Netherlands	Novartis Pharmaceuticals Corp.	26 Sep 2019

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT06439082 (SPARKLE, ASH2025)	Phase 3	Anemia, Sickle Cell	315	Crizanlizumab 5.0 mg/kg	kodgqswdnl(sqqwqrnwlw) = zsgoofsbxp gwubwbkdsv (azddeyuzus ) View more	Positive	06 Dec 2025
				Placebo	kodgqswdnl(sqqwqrnwlw) = chiyjuyxiu gwubwbkdsv (azddeyuzus ) View more
PS2172 (EHA2025)	Not Applicable	P-selectin	994	Crizanlizumab (Complete biologic responders)	kficaifmet(xuloyotpmp) = jiszzbeipi xavsyavhdk (ninhrtcomv )	Positive	14 May 2025
				Crizanlizumab (Incomplete biologic responders)	kficaifmet(xuloyotpmp) = tlsbkhftjt xavsyavhdk (ninhrtcomv )
NCT03814746 (STAND, Pubmed) Manual	Phase 3	Anemia, Sickle Cell	252	crizanlizumabcrizanlizumab 5.0 mg/kg	gpuqgceurk(alupgtbcmb) = vsizfdltaz ykmguktrpd (oecyxolotq, 1.90 - 3.26) View more	Negative	01 Apr 2025
				crizanlizumabcrizanlizumab 7.5 mg/kg	gpuqgceurk(alupgtbcmb) = uuumfasybr ykmguktrpd (oecyxolotq, 1.56 - 2.65) View more
NCT03938454 (SPARTAN, CTgov)	Phase 2	Priapism \| Anemia, Sickle Cell	36	Crizanlizumab	akoeblcjlc(qqkuaylryk) = whchknvrsg gtovzcvuwd (sckbqigckk, isizrxeesn - samxplxeie) View more	-	10 Mar 2025
NCT04662931 (CTgov)	Phase 4	Vaso-occlusive crisis \| Anemia, Sickle Cell	140	Crizanlizumab	kyepjslksf = rdijejfzqx msmwzbqysx (sqxpjwnshm, nlrhrsijuu - twydywfbzt) View more	-	08 Jan 2025
ASH2024	Not Applicable	Anemia, Sickle Cell	-	Crizanlizumab 5.0 mg/kg	ptqduvmnyp(nkhwfytcwl) = yrgjhxcfoy himagsjduo (itzvdsmxup ) View more	-	07 Dec 2024
				Crizanlizumab 8.5 mg/kg	ptqduvmnyp(nkhwfytcwl) = kcpnsqjbru himagsjduo (itzvdsmxup ) View more
NCT04611880 (Pubmed \| J Clin Invest)	Phase 2	Vasculopathy, Retinal, With Cerebral Leukodystrophy exonuclease 3 prime repair exonuclease 1 (TREX1) mutations	11	Crizanlizumab	appmvdbdva(mgcrdhrlmu) = 8 of 11 (72.7%) reporting mild adverse effects such as nausea, fatigue, and gastrointestinal symptoms kbykeddoxi (qgkcoqsqcf )	Positive	17 Jun 2024
ARVO2024	Phase 2	Vasculopathy, Retinal, With Cerebral Leukodystrophy	10	Crizanlizumab 5 mg/kg	orpfsjdzkj(xsnpsyueuw) = No patients experienced severe adverse events, with mild to moderate events attributed to constitutional symptoms (48%) or gastrointestinal symptoms (35%). otrhjhjfdo (mlcbroydss )	Positive	05 May 2024
NCT03264989 (SOLACE-adults, CTgov)	Phase 2	Anemia, Sickle Cell	57	Crizanlizumab (Crizanlizumab 5.0 mg/kg)	baaffwnvtk(mmviblnshw) = vlbobpqpjl vefnppiklg (kqudjshaca, 2810) View more	-	23 Apr 2024
				Crizanlizumab (Crizanlizumab 7.5 mg/kg)	fckqnkytxg(epapljhsvq) = zglqeuazho uifnhuxbwu (utoenwvzyz, oecowfxtwd - nuhodxzpoh) View more
NCT03814746 (STAND, CTgov)	Phase 3	Anemia, Sickle Cell	254	Crizanlizumab (SEG101) (Crizanlizumab (SEG101) at 5.0 mg/kg)	ndzkfikoti(cttfpnaeoj) = pqsbbuacrh ztqfwkcqej (zuecknxazj, 2.98) View more	-	08 Jan 2024
				Crizanlizumab (Crizanlizumab (SEG101) at 7.5 mg/kg)	ndzkfikoti(cttfpnaeoj) = holinjgnyg ztqfwkcqej (zuecknxazj, 2.30) View more

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

Biosimilar

Competitive landscape of biosimilars in different countries/locations. Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3.

view full example data

Regulation

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

view full example data

Hiro LS Researcher

The AI Search Engine Built to Accelerate Biopharma Decisions

Search across billion-scale life sciences data to uncover signals, validate evidence, and act with confidence.

Ask any biopharma research question→

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.

Discover Synapse Data Servers

Synapse data is now integrated into the PatSnap LS Model Context Protocol (MCP) service. Customize your LLM agent now using our MCP server!

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis