Multi-Centric Castleman's Disease

BEIJING--( BUSINESS WIRE )--Latest data of InnoCare’s (HKEX: 09969; SSE: 688428) orelabrutinib were presented at the ongoing 66th American Society of Hematology (ASH) Annual Meeting. Poster Presentation 1. Orelabrutinib in Patients with Indolent Non-Hodgkin Lymphoma (iNHL) Who Are Intolerant to Prior Bruton Tyrosine Kinase Inhibitors (BTKi): Updated Results from a Phase 2 Study (Abstract No.: 4399) Orelabrutinib improved outcomes of prior BTKi-intolerant adverse events (AEs), particularly the off-target toxicities. Patients who switched experienced minimal and low levels of intolerance recurrences and all achieved disease control. These updated results show promising efficacy and safety data of orelabrutinib in prior BTKi-intolerant iNHL patients. As data cutoff (July 9, 2024), 66 patients were enrolled and 64 patients were available for AE and efficacy analysis. At a median follow-up of 6.8 months, the median progression-free survival (PFS) and overall survival (OS) were not reached. Both PFS and OS rates remained 100%. 2. Orelabrutinib, Fludarabine, Cyclophosphamide, and Obinutuzumab (OFCG) for First-Line Treatment of Chronic Lymphocytic Leukemia: A Multicenter, Investigator-Initiated Study (cwCLL-001 Study) (Abstract No.: 3244) This is a multicenter, open-label, non-randomized phase II study for previously untreated patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) without restriction by del(17p)/TP53 aberrations and/or immunoglobulin heavy⁃chain variable region gene (IGHV) mutation status. The Orelabrutinib, Fludarabine, Cyclophosphamide, and Obinutuzumab regimen leads to a rapid and deep molecular remission with a manageable safety profile in previously untreated CLL patients including those with unfavorable characteristics. After cycle 6, the rates of peripheral blood (PB) undetectable minimal residual disease (uMRD) and bone marrow (BM) uMRD by flow cytometry (FCM) were 95% and 86%, respectively, and the rate of complete response (CR)/CR with incomplete hematologic recovery (CRi ) was 59%. After cycle 12, the rates of PB-uMRD by FCM, BM-uMRD by FCM, and CR/CRi were 95%, 91% and 77% respectively. 3. A Prospective, Multicenter, Single-Arm Study on the Combination of Orelabrutinib and Rituximab in the Second-Line Treatment of Relapsed/Refractory Marginal Zone Lymphoma (Abstract No.: 4391) This is a prospective, multicenter, single-arm, phase II clinical trial, aiming to evaluate the efficacy and safety of orelabrutinib in combination with rituximab in patients with relapsed or refractory Marginal Zone Lymphoma (MZL). The preliminary results of this study suggest that the combination therapy of orelabrutinib and rituximab is effective in patients with rrMZL and has manageable safety, with tolerable maintenance therapy. Of the 12 enrolled patients, 6 have completed the interim efficacy assessment, achieving an overall response rate (ORR) of 100%. 3 patients completed the combination therapy and entered the maintenance phase, keeping the ORR at 100%. All patients chose orelabrutinib for maintenance therapy. 4. Orelabrutinib, Rituximab, and Thiotepa (ORT) in Combination with or without High-Dose Methotrexate in Untreated Primary Central Nervous System Lymphoma (Abstract No.: 4487) The orelabrutinib, rituximab, and thiotepa (ORT) regimen, with or without high-dose methotrexate (HD-MTX), has shown initial efficacy and a manageable safety profile in treating Primary Central Nervous System Lymphoma (PCNSL), particularly in elderly patients with MCD subtypes. Autologous stem cell transplantation (ASCT) following ORT with or without HD-MTX induction therapy further improves patient response. Patients with complete response (CR) did not relapse and were well-tolerated on orelabrutinib maintenance therapy. The median follow-up was 8.27 months. The best CR rate was 85.71%, and the longest CR duration was 22.53 months. The objective response rate (ORR) was 85.71%. 5. Preliminary Data of a Single-Arm, Phase II Study of Orelabrutinib with/without Rituximab in Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma after BTK Inhibitor Therapy (Abstract No.: 3240) Despite the currently limited follow-up period, orelabrutinib combined with or without rituximab, demonstrated favorable efficacy in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) patients with detectable MRD post-BTK inhibitor treatment, and MRD decreased significantly after 9 months. This treatment holds the potential to emerge as a new therapeutic option for CLL/SLL patients. At 9 months, 66.7% achieved undetectable peripheral blood MRD, with a 9-month complete response rate (CRR) of 77.8% and a 1-year overall survival (OS) of 100%, and no patient has progressed thus far. 6. Preliminary Data on the Efficacy and Safety of Orelabrutinib Combined with Rituximab and Methotrexate (ORM Regimen) As First-Line Treatment for Primary Central Nervous System Lymphoma, and the Exploration of Cerebrospinal Fluid ctDNA Dynamic Monitoring (Abstract No.: 4500) The Orelabrutinib Combined with Rituximab and Methotrexate regimen demonstrates high overall response rate (ORR) and complete response (CR) in the treatment of Primary Central Nervous System Lymphoma (PCNSL), with acceptable safety. Our results suggest that dynamic monitoring of cerebrospinal fluid circulating tumor DNA (ctDNA) is of significant importance for the early evaluation of therapeutic efficacy and prognosis prediction in PCNSL. During treatment the best response evaluation showed an ORR of 86.4% and a disease control rate (DCR) of 100%; Among the 21 patients who completed all induction therapies, the ORR was 85.71% with a CR rate of 76.19%. Among 19 patients with detectable ctDNA in baseline CSF, 13 patients had undetectable ctDNA in C5D1 CSF, of which 12 patients achieved CR. Patients with undetectable CSF ctDNA at C5D1 showed longer progression-free survival (PFS), indicating that early clearance of CSF ctDNA can predict favorable prognosis. 7. Preliminary Efficacy of Orelabrutinib Targeted Therapy in Induction Therapy of Primary Central Nervous System Diffuse B-Cell Lymphoma (Abstract No.: 4496) The Orelabrutinib, Rituximab and High-dose MTX regimen is an effective and safe induction therapy for primary central nervous system diffuse B-cell lymphoma, with a total response rate of 83.3% and a median onset time of 1 course for partial response (PR) and 2 courses for complete response (CR). It is a promising induction therapy for primary central nervous system diffuse B-cell lymphoma. 8. The Primary Results of R-MTO Regimen (Rituximab, Methotrexate, Thiotepa, and Orelabrutinib) As the First-Line Induction Therapy Followed By Autologous Stem Cell Transplantation in Newly Diagnosed Primary Central Nervous System Lymphoma (Abstract No.: 1742) This is a prospective designed, ongoing, single-center, single-arm, open-label study. The Rituximab, Methotrexate, Thiotepa, and Orelabrutinib induction treatment has demonstrated notable efficacy in achieving higher response rates among patients with newly diagnosed Primary Central Nervous System Lymphoma (PCNSL), and a tolerable safety profile. A total of 26 patients with newly diagnosed PCNSL were enrolled in this study. The overall response rate (ORR) was 96.15%, and the complete response (CR) rate was 92.30% after 4 cycles of treatment. Among ten patients who underwent autologous hematopoietic stem cell transplantation (HSCT), all of them (100%) remained in CR. The progression-free survival (PFS) and overall survival (OS) rate at 12 months were 82.24%, and 87.00% respectively. 9. Efficacy and Safety of Orelabrutinib in Relapsed/Refractory Idiopathic Multicentric Castleman Disease: A Single-Center, Retrospective Study (Abstract No.: 1656) Orelabrutinib, with its high response rate, durable response time, and improved safety profile can be a viable alternative for the treatment of patients with relapsed/refractory (r/r) idiopathic multicentric Castleman disease (iMCD). Ten patients with r/r iMCD were included in the study, Seven patients (70%) were assessed as responders, two of whom achieved complete response. The median time to remission for responders was 9.8 months (range: 5.9–20.5 months). In the non-responder group, despite not achieving response criteria, these patients still showed a continuous improvement in median hemoglobin, albumin, C-reactive protein (CRP) and creatine levels with treatment at month 12. No grade 3 or above adverse reactions occurred. Except poster presentation, more than 10 studies were also selected as online publications at the meeting. For more detailed clinical data, please refer to ASH website. About InnoCare InnoCare (HKEX: 09969; SSE: 688428) is a commercial stage biopharmaceutical company committed to discovering, developing, and commercializing first-in-class and/or best-in-class drugs for the treatment of cancer and autoimmune diseases with unmet medical needs in China and worldwide. InnoCare has branches in Beijing, Nanjing, Shanghai, Guangzhou, Hong Kong, and United States. InnoCare Forward-looking Statements This report contains the disclosure of some forward-looking statements. Except for statements of facts, all other statements can be regarded as forward-looking statements, that is, about our or our management's intentions, plans, beliefs, or expectations that will or may occur in the future. Such statements are assumptions and estimates made by our management based on its experience and knowledge of historical trends, current conditions, expected future development and other related factors. This forward-looking statement does not guarantee future performance, and actual results, development and business decisions may not match the expectations of the forward-looking statement. Our forward-looking statements are also subject to a large number of risks and uncertainties, which may affect our short-term and long-term performance.

Sanofi’s Enjaymo, the only approved drug therapy for a rare and debilitating blood disorder, is being acquired by Recordati in a deal that helps the Italian company build its rare disease portfolio and expand its commercial reach in key markets. Recordati is paying $825 million up front for global rights to Enjaymo, a drug that is approved in the U.S., Japan, and Europe. If the drug achieves sales milestones, the company could pay out up to $275 million more, according to deal terms announced Friday. Sanofi and Recordati expect to complete the transaction by the end of this year. Enjaymo treats cold agglutinin disease, a condition in which the immune system attacks red blood cells and causes them to rupture. This process happens at cold temperatures, giving the disease its name. At these temperatures, antibodies that normally attack bacteria instead attach to red blood cells, causing them to bind together, or agglutinate. The red blood cells are destroyed by the immune system, leading to anemia. presented by Health Tech What’s Keeping Healthcare CIOs Up at Night: How to Improve Patient Satisfaction by Handling Calls More Efficiently Health systems have spent billions on portals while investments in modernizing the voice channel — the dominant preference of healthcare consumers — have taken a backseat. By Stephanie Baum The resulting anemia can be managed with blood transfusions. Enjaymo takes a different approach by interfering with the process that leads to red blood cell destruction in cold agglutin disease. The drug, an intravenously infused monoclonal antibody, is designed to selectively target and block a complement system protein called C1. This in turn stops immune system antibodies from attaching to immune cells. The FDA approved Enjaymo in 2022. Approvals in Japan and Europe soon followed. In these three markets, the companies estimate cold agglutin disease affects between 11,000 and 12,000 patients. Recordati, which is headquartered in Milan, is the latest stop in a long journey for Enjaymo. The drug was initially developed by True North Therapeutics, which itself was acquired by Bioverativ in 2017. In 2018, Sanofi paid $11.6 billion to buy Bioverativ. Enjaymo generated €72 million (about $79 million) in sales last year, a 240% increase over the product’s sales in 2022, according to Sanofi’s annual report. Sales for Enjaymo are continuing to grow, but it’s not on track to become a blockbuster seller. Recordati said that in the 12 months ending in August, the drug accounted for €100 million (about $109 million) in revenue. The company projects the product’s peak sales could reach €250 million to €300 million (about $274 million to $328 million). Recordati said its milestone payment to Sanofi is tied to the achievement of net sales at or above the top end of peak year sales expectations. Rare disease accounts for about 34% of Recordati’s more than €2 billion in annual revenue, according to a September investor presentation. Most of those rare disease sales are in the U.S. Much of the company’s rare disease portfolio is comprised of assets from its 2022 acquisition of EUSA Pharma, a developer of drugs for rare cancers. Sponsored Post Get Ready for HLTH 2024: A Preview Guide HLTH 2024, scheduled for October 20-23 at the Venetian Expo Center in Las Vegas, will highlight new programming, a physicians roundtable, generative AI, the shifting landscapes of telemedicine, retail health, women's health, and lots more. By Stephanie Baum In a prepared statement, Recordati CEO Rob Koremans said Enjaymo is particularly complementary to one of those products, Sylvant. This drug, an antibody designed to block the inflammatory signaling protein IL-6, has approvals in more than 40 countries for treating idiopathic multicentric Castleman disease, a rare disorder characterized by abnormal growth of the lymph nodes. While this disease is not cancer, its progression is similar to that of lymphoma, a cancer of the lymph nodes. Last year, Recordati began exploring the development of Sylvant for other diseases driven by IL-6 signaling. “Enjaymo further expands our rare diseases footprint in the U.S., Japan and Europe, and will contribute positively to both our top and bottom lines,” Koremans said. “Most importantly, with a strong clinical profile and as the only product approved for the treatment of [cold agglutinin disease], Enjaymo addresses a serious unmet medical need for patients living with this debilitating disease.” Image by istocksdaily, via Getty Images

Researchers have developed a model of Kaposi sarcoma that could expedite the development of new drugs to treat the disease, which is the most common cancer in people living with HIV. Researchers at UNC Lineberger Comprehensive Cancer Center, after decades of research efforts, have developed a mouse model of Kaposi sarcoma that could be key to the development of new drugs to treat the disease. Kaposi sarcoma is a cancer that is the most common cancer in people living with HIV. The findings appeared in Cell Host & Microbe. "This is an important development as we have created the first animal model ever of Kaposi sarcoma. Animal models are essential to move new drugs from the laboratory bench into clinical trials," said UNC Lineberger's Dirk Dittmer, PhD, senior corresponding author, co-leader of the UNC Lineberger Virology Research Program and director of the UNC Viral Genomics Core. "Before this, only repurposed drugs from other cancers were used to treat Kaposi sarcoma, but now we can start investigating entirely new compounds to help treat what can be a lethal cancer." About 20% of all human cancers arise from viruses or require viral infection as an essential cofactor. The Kaposi sarcoma-associated herpes virus (KSHV) was discovered in 1994 and is associated with Kaposi's sarcoma as well as B-cell cancers. KSHV-associated diseases affect internal organs and are ultimately fatal. In the U.S., the diseases are found primarily in immunosuppressed people such as those who are HIV-positive or are transplant patients. Worldwide, an estimated 34,270 cases of Kaposi sarcoma were diagnosed, and 15,086 deaths reported in 2020, with twice as many cases and deaths occurring in men compared to women. Africa accounted for 73% of new cases and 86.6% of the deaths from Kaposi sarcoma worldwide. The disease is endemic, and not HIV-related, in some southern and eastern African countries. Aside from animal models, one way to study cancer is to look at tumor cells in the lab. But according to Dittmer, Kaposi sarcoma tumor cells are very finicky and dependent on signaling molecules and blood supply, which is why they don't survive in a laboratory culture dish. Therefore, researchers have been focusing on developing animal models that would mimic, as closely as possible, the disease in humans. One of the challenges the researchers faced in developing their model was the fact that two types of genes are transcribed into proteins in the Kaposi sarcoma mouse model. Normally when a virus infects a cell, the cell dies as the virus replicates, which is a process called cell lysis; the genes that are needed for the virus to propagate itself are lytic genes. Cancer viruses are different as they enter a quiet state, called latency, where only the genes that help the infected cell survive are expressed. The mouse model the researchers developed is complex as a bit of both types of genes were needed. Cervical cancer and its related virus, HPV (human papilloma virus), offers a good comparison for the challenge of developing a Kaposi sarcoma mouse model. The KSHV genome is 20 times larger than HPV. HPV has two cancer-causing genes, E6 and E7, so to mimic the disease in animals, researchers only needed to design two mice, one for each gene. KSHV may have as many as 10 cancer-causing genes that all work together so it would be way too difficult to develop that many mice, hence the virtue of their single model, Dittmer noted. "Another of the key virtues of our new mouse model is that it helps us understand angiogenesis, or new blood vessel formation. Without angiogenesis cancer cells are deprived of oxygen and die," Dittmer said. "In this mouse model, we can study angiogenesis blocking drugs better than ever before. If new drugs work against Kaposi sarcoma, they will also likely work against lesser-angiogenic tumors, which would be a major plus." For next steps, the researchers hope that others will pursue drug and vaccine development based on a new understanding of fundamental aspects of KSHV provided by their mouse model, including possible development of a much-needed primate model for human KSHV and Kaposi sarcoma.