Linvoseltamab Pivotal Data Presented at AACR Reinforce High Response Rate that Deepens Over Time in Patients with Heavily Pre-Treated Multiple Myeloma
- Positive pivotal data presented for linvoseltamab in patients with relapsed/refractory multiple myeloma.
- 71% objective response rate with 46% achieving a complete response and 62% achieving a very good partial response.
- Median duration of response, progression-free survival, and overall survival not reached at 11-month follow-up.
- 93% of patients who achieved a complete response were minimal residual disease negative at 10-5.
- High objective response rates observed across various subgroups, including high-risk populations.
- Linvoseltamab showed a good safety profile with manageable adverse events.
- Fast Track Designation and Priority Review granted by the FDA with a target action date of August 22, 2024.
- Phase 3 confirmatory trial (LINKER-MM3) for linvoseltamab in patients with relapsed/refractory multiple myeloma ongoing.
- 46% of patients experienced cytokine release syndrome as the most common treatment-emergent adverse event.
- Infections occurred in 73% of patients, with 34% being Grade 3 or 4.
- Six deaths occurred on treatment or within 30 days of the last dose due to treatment-emergent adverse events.
- Safety and efficacy of linvoseltamab have not been fully evaluated by any regulatory authority.
Insights
The recent data from the Phase 1/2 LINKER-MM1 trial of linvoseltamab for the treatment of relapsed/refractory multiple myeloma presented at AACR is a significant milestone in oncology therapeutics. The reported 71% objective response rate and 46% complete response rate are notable, particularly in a patient population that has limited treatment options. These results may suggest a strong potential for linvoseltamab to become a key player in the multiple myeloma treatment landscape, pending regulatory approval.
Furthermore, the response-adapted dosing regimen presents a potential improvement in patient quality of life by reducing the frequency of dosing upon achieving a very good partial response. This innovation could lead to better patient adherence and reduced healthcare costs associated with treatment administration. However, the occurrence of cytokine release syndrome in 46% of patients and infections in 73% of patients raises safety concerns that may need to be addressed through careful patient monitoring and management strategies.
The clinical efficacy of linvoseltamab, as evidenced by the high rates of complete response and very good partial response, is impressive and could represent a breakthrough in the treatment paradigm for multiple myeloma. The depth and durability of responses, coupled with the favorable safety profile, particularly the manageable rates of Grade 3 or higher adverse events, suggest that linvoseltamab could offer a substantial benefit to patients. The MRD negativity in 93% of evaluable patients who achieved a complete response is a strong predictor of long-term outcomes and could potentially set a new standard for therapeutic success in this disease.
Regeneron Pharmaceuticals' linvoseltamab, if approved, could capture a significant share of the multiple myeloma market, which is characterized by high unmet needs for effective and durable treatments. The Fast Track Designation and Priority Review status by the FDA indicate the therapy's potential to address these needs. The market impact could be substantial, as investors and stakeholders closely watch the FDA's decision expected in August. The successful development of linvoseltamab may also lead to an increase in Regeneron's market valuation and could attract further investment in bispecific antibody technologies for cancer treatment.
Regulatory applications for linvoseltamab currently under review by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA)
TARRYTOWN, N.Y., April 07, 2024 (GLOBE NEWSWIRE) -- Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced the oral plenary session presentation of positive pivotal data from the Phase 1/2 LINKER-MM1 trial of linvoseltamab in patients with relapsed/refractory (R/R) multiple myeloma (MM) at the American Association for Cancer Research (AACR) Annual Meeting 2024 in San Diego. Linvoseltamab is an investigational bispecific antibody designed to bridge B-cell maturation antigen (BCMA) on multiple myeloma cells with CD3-expressing T cells to facilitate T-cell activation and cancer-cell killing.
“The presentation of these pivotal results in an oral plenary session at AACR recognizes the exciting potential of linvoseltamab to advance the treatment of multiple myeloma,” said Sundar Jagannath, M.D., Director of the Multiple Myeloma Center of Excellence at Tisch Cancer Center at Mount Sinai in New York City and a trial investigator. “In clinical trials, linvoseltamab treatment led to responses that occurred early, were durable and deepened over time – all critical efficacy measures for this heavily pre-treated patient population. Further, among patients who had at least 24 weeks of treatment, the majority achieved a very good partial response, enabling them to transition from every two-week to every four-week dosing. This is an important accomplishment that I’ve seen firsthand in my trial patients, and I eagerly anticipate the FDA decision expected this August.”
With an 11-month median duration of follow up, the linvoseltamab data among 117 patients presented at AACR reinforce the strength of previously shared findings and included a:
71% objective response rate (ORR), with46% of patients achieving a complete response (CR) or better and62% achieving a very good partial response (VGPR) or better, as determined by an independent review committee.- 1-month median time to response (range: <1-6 months). In responders, the median time to a VGPR or better was 3 months (range: <1-13 months) and to a CR or better was 8 months (range: 2-14 months).
- Median duration of response (DoR), median progression-free survival (PFS) and median overall survival (OS) were not reached. At 12 months, the estimated probability of maintaining a response was
78% , being progression free was69% and survival was75% . - Among patients who had a CR or better and were minimum residual disease (MRD) evaluable,
93% (25 of 27 patients) were MRD negative at 10-5.
The trial included a response-adapted regimen that enabled linvoseltamab patients to shift to every four-week dosing if they achieved a VGPR or better and completed at least 24 weeks of therapy. In the dose expansion portion of the trial (n=105), of the patients who had at least 24 weeks of therapy at data cutoff,
In addition, high ORRs were observed across prespecified subgroups – including high-risk and high-disease burden populations – as follows:
85% among Black or African American patients (17 of 20 patients)71% among those aged 75 years or older (22 of 31 patients)67% among those with high cytogenetic risk (31 of 46 patients)62% among those with International Staging System stage III disease (13 of 21 patients)53% among those with extramedullary plasmacytomas (10 of 19 patients)
Cytokine release syndrome (CRS) was the most commonly occurring treatment-emergent adverse event (TEAE) and was observed in
Linvoseltamab has been granted Fast Track Designation and was accepted for Priority Review for the treatment of R/R MM by the FDA, with a target action date of August 22, 2024. In addition, linvoseltamab is being reviewed by the EMA. Linvoseltamab is currently under clinical development, and its safety and efficacy have not been fully evaluated by any regulatory authority.
The Phase 3 confirmatory trial for linvoseltamab in patients with R/R MM (LINKER-MM3) is underway.
About Multiple Myeloma
As the second most common blood cancer, there are over 176,000 new cases of MM diagnosed globally, and 35,000 cases are diagnosed in the U.S. every year. In the U.S., there are approximately 8,000 people who have MM that has progressed after three lines of therapy, and 4,000 whose disease has progressed after four or more therapies. The disease is characterized by the proliferation of cancerous plasma cells (MM cells) that crowd out healthy blood cells in the bone marrow, infiltrate other tissues and cause potentially life-threatening organ injury. Despite treatment advances, MM is not curable and while current treatments are able to slow progression of the cancer, most patients will ultimately experience cancer progression and require additional therapies.
About the Linvoseltamab Phase 1/2 Trial and Clinical Development Program
The ongoing, open-label, multicenter Phase 1/2 dose-escalation and dose-expansion LINKER-MM1 trial is investigating linvoseltamab in 282 enrolled patients with relapsed/refractory MM. The Phase 1 dose-escalation portion of the trial – which is now complete – primarily assessed safety, tolerability and dose-limiting toxicities across nine dose levels of linvoseltamab and explored different administration regimens. The ongoing Phase 2 dose expansion portion is assessing the safety and anti-tumor activity of linvoseltamab, with the primary endpoint of ORR. Key secondary endpoints include DoR, PFS, rate of MRD negative status and OS.
Eligibility in the Phase 2 portion requires patients to have received at least three prior lines of therapy or have triple-class refractory MM. Linvoseltamab is administered with an initial step-up dosing regimen followed by the full 200 mg dose administered weekly. At week 16, all patients transition to every two-week dosing. A response-adapted regimen further enables patients to shift to every four-week dosing if they achieve a VGPR or better and have completed at least 24 weeks of therapy. The regimen requires a total of two 24-hour hospitalizations for safety monitoring.
The broader linvoseltamab clinical development program includes additional trials in earlier lines of therapy and stages of disease that are planned or underway. They include a Phase 1/2 trial in first-line MM, a Phase 2 trial in high-risk smoldering MM, and a Phase 2 trial in monoclonal gammopathy of undetermined significance. A Phase 1 trial of linvoseltamab in combination with a Regeneron CD38xCD28 costimulatory bispecific in MM is also planned. For more information, visit the Regeneron clinical trials website, or contact via clinicaltrials@regeneron.com or 844-734-6643.
About Regeneron in Hematology
At Regeneron, we’re applying more than three decades of biology expertise with our proprietary VelociSuite® technologies to develop medicines for patients with diverse blood cancers and rare blood disorders.
Our blood cancer research is focused on bispecific antibodies that are being investigated both as monotherapies and in various combinations and emerging therapeutic modalities. Together, they provide us with unique combinatorial flexibility to develop customized and potentially synergistic cancer treatments.
Our research and collaborations to develop potential treatments for rare blood disorders include explorations in antibody medicine, gene editing and gene-knockout technologies, and investigational RNA-approaches focused on depleting abnormal proteins or blocking disease-causing cellular signaling.
About Regeneron
Regeneron is a leading biotechnology company that invents, develops and commercializes life-transforming medicines for people with serious diseases. Founded and led for over 35 years by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to numerous FDA-approved treatments and product candidates in development, almost all of which were homegrown in our laboratories. Our medicines and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, hematologic conditions, infectious diseases and rare diseases.
Regeneron is accelerating and improving the traditional drug development process through our proprietary VelociSuite technologies, such as VelocImmune®, which uses unique genetically humanized mice to produce optimized fully human antibodies and bispecific antibodies, and through ambitious research initiatives such as the Regeneron Genetics Center®, which is conducting one of the largest genetics sequencing efforts in the world.
For more information about Regeneron, please visit www.Regeneron.com or follow Regeneron on LinkedIn.
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