Shots:
- Lynozyfic is emerging as a standout in heavily pre-treated multiple myeloma. In the pivotal LINKER-MM1 trial, it delivered early, deep, and durable responses, offering renewed hope for patients with limited options. Its response-adapted dosing regimen further reduces treatment burden and enhances convenience
- Regeneron is accelerating progress with a broad development strategy, advancing Lynozyfic across multiple therapy lines, combination regimens, precursor conditions, and global markets. The program integrates MRD as a key biomarker and reinforces patient safety through a comprehensive REMS program
- Karen Rodriguez Lorenc, Vice President and Therapeutic Area Lead for Hematology Oncology at Regeneron, highlights major milestones ahead, including the Phase 3 LINKER-MM3 confirmatory trial, EU commercialization in 2025, expanded global access efforts, and a growing pipeline of studies. These initiatives aim to position Lynozyfic earlier in the treatment journey and enhance outcomes for patients worldwide
Saurabh: Lynozyfic has recently emerged as a new option for heavily pre-treated multiple myeloma patients. In your view, what sets it apart from other therapies currently available for this challenging patient group?
Karen: There are no head-to-head studies comparing Lynozyfic to any therapies, so we are unable to make any comparative conclusions about efficacy or safety.
We believe Lynozyfic offers a differentiated profile. The FDA approval was based on results from the pivotal Phase 1/2 LINKER-MM1 trial, in which Lynozyfic demonstrated early, deep and durable responses in R/R MM in which patients (n=80) experienced a:
- 70% objective response rate (ORR), with 45% achieving a complete response (CR) or better, as determined by an independent review committee.
- 0.95 month median time to first response (range: 0.5 to 6 months).
- Median duration of response (DoR) that was not reached (95% Confidence Interval [CI]: 12 months to not estimable). The estimated DoR was 89% at 9 months (95% CI: 77 to 95 months) and 72% at 12 months (95% CI: 54 to 84 months) among responders who had a median follow-up of 13 months.
The prescribing information for Lynozyfic has a Boxed Warning for cytokine release syndrome (CRS) and neurologic toxicity – including immune effector cell-associated neurotoxicity syndrome – in addition to warnings and precautions for infections, neutropenia, hepatotoxicity and embryo-fetal toxicity. The most common adverse reactions (≥20%) in the safety population of LINKER-MM1 (n=117) were musculoskeletal pain, CRS, cough, upper respiratory tract infection, diarrhea, fatigue, pneumonia, nausea, headache and dyspnea. The most common Grade 3 or 4 laboratory abnormalities (≥30%) were decreased lymphocyte count, decreased neutrophil count, decreased hemoglobin and decreased white blood cell count.
Saurabh: Could you walk me through how the response-adapted dosing regimen for Lynozyfic works in practice? What advantages does this approach offer for patients, especially regarding treatment burden and their overall quality of life?
Karen: Patients treated with Lynozyfic will start with an initial step-up dosing regimen followed by the full 200 mg dose administered weekly. Per label, at week 14, patients transition to every two-week dosing. This regimen further enables patients to shift to every four-week dosing if they achieve and maintain a very good partial response or better after having completed at least 24 weeks of therapy and 17 full doses. This dosing schedule can potentially help alleviate treatment burden by reducing the amount of time patients need to spend at planned doctor’s appointments over the course of treatment, which may be particularly beneficial for older patients.
Saurabh: Multiple myeloma remains an incurable disease with significant unmet needs, particularly for those who have exhausted several lines of therapy. How does Lynozyfic address these challenges and offer hope for patients in this situation?
Karen: Multiple myeloma (MM) is the second most common blood cancer, and despite all the treatments available, patients are still progressing after four or more lines of therapy.
Lynozyfic provides a new treatment option for patients with relapsed or refractory (R/R) MM that have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an antiCD38 monoclonal antibody. Additionally, the response-adapted dosing schedule may be convenient for patients.
Saurabh: Are there ongoing or future plans to investigate Lynozyfic’s use earlier in the treatment pathway or in combination with other therapies?
Karen: Lynozyfic (linvoseltamab) is being investigated in a broad clinical development program exploring its use as a monotherapy as well as in combination regimens across different lines of therapy in MM, including earlier lines of treatment, as well as plasma cell precursor disorders. Trials include:
- LINKER-MM1: Phase 1/2 dose-escalation and dose-expansion trial evaluating the safety, tolerability, dose-limiting toxicities and anti-tumor activity of linvoseltamab monotherapy in R/R MM
- LINKER-MM2: Phase 1b trial evaluating linvoseltamab in combination with other cancer treatments, including standard of care therapies and novel therapies such as immunomodulatory drugs, proteasome inhibitors, anti-CD38 antibodies, checkpoint inhibitors and a gamma secretase inhibitor, in R/R MM
- LINKER-MM3: Phase 3 confirmatory trial evaluating linvoseltamab monotherapy compared to the combination of elotuzumab, pomalidomide and dexamethasone in R/R MM
- Phase 1 trial evaluating linvoseltamab in combination with a Regeneron CD38xCD28 costimulatory bispecific in R/R MM
- LINKER-MM4: Phase 1/2 trial evaluating linvoseltamab monotherapy in newly diagnosed MM
- LINKER-SMM1: Phase 2 trial evaluating linvoseltamab monotherapy in high-risk smoldering MM (SMM)
- LINKER-MGUS1: Phase 2 dose-ranging trial evaluating linvoseltamab monotherapy in high-risk monoclonal gammopathy of unknown significance and non-high-risk SMM
- LINKER-AL2: Phase 1/2 trial evaluating linvoseltamab monotherapy in R/R systemic light chain amyloidosis
Saurabh: Are there any additional biomarkers or patient characteristics being studied to optimize patient selection and personalize Lynozyfic treatment?
Karen: Yes, we are evaluating minimal residual disease (MRD) status in patients treated with Lynozyfic.
This is an important measure that can aid in predicting whether a patient can experience longer progression-free and overall survival outcomes. Last year, the FDA’s Oncologic Drugs Advisory Committee voted unanimously that the totality of available data supports the use of MRD as an end point for accelerated approval of new treatments for patients with MM making it an important measure in our current and future trials.
Saurabh: Patient safety is always a top priority, especially with novel therapies. Can you share the key components of the Lynozyfic Risk Evaluation and Mitigation Strategy (REMS), and how Regeneron is working to ensure patient safety during treatment?
Karen: Lynozyfic has a REMS program with the goal of mitigating the risks of cytokine release syndrome (CRS) and neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS). Key requirements of our program include:
- Prescribers must be certified with the program by enrolling and completing training.
- Prescribers must counsel patients receiving Lynozyfic about the risk of CRS and neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS), and provide patients with a Lynozyfic Patient Wallet Card.
- Pharmacies and healthcare settings that dispense Lynozyfic must be certified with the Lynozyfic REMS program and must verify prescribers are certified through the Lynozyfic REMS program.
- Wholesalers and distributors must only distribute Lynozyfic to certified pharmacies or healthcare settings.
More information is available at LynozyficREMS.com.
Saurabh: The recent approval of Lynozyfic in the EU is a significant milestone. How has this influenced Regeneron’s strategy for expanding global access and developing patient support programs?
Karen: This is an important year for Regeneron’s Hematology Oncology teams. Following the recent EU approval of Lynozyfic, we intend to commercialize the therapy in Germany in 2025, subject to product manufacturing and availability. We also recently launched Ordspono in Germany. These milestones contribute greatly to our growing oncology portfolio and goal of supporting patients in the EU living with difficult-to-treat blood cancers.
Looking ahead, we are continuing to take a measured approach to our international expansion and will work with the proper parties in each market to provide appropriate patient support programs like our U.S. program, Lynozyfic Surround, which offers financial and educational resources to support patients throughout their treatment journey.
Saurabh: Could you elaborate on the primary objectives and design of the Phase 3 confirmatory trial, and what key outcomes Regeneron hopes to demonstrate to support full regulatory approval for Lynozyfic in relapsed or refractory multiple myeloma?
Karen: The Phase 3 LINKER-MM3 trial is an open-label, randomized study investigating linvoseltamab as a monotherapy compared to the combination of elotuzumab, pomalidomide and dexamethasone (EPd) in adult patients with R/R MM. The aim of the LINKER-MM3 trial is to evaluate the safety and efficacy of linvoseltamab compared to EPd in participants who have received prior treatment, including lenalidomide, a proteosome inhibitor and, for participants in some countries, a CD38 antibody.
The primary endpoint is progression-free survival. Key secondary endpoints include objective response rate, minimal residual disease negative status, overall survival, and change in pain at Week 12. Incidence and severity of treatment-emergent AEs will also be assessed.
Our hope is that the Phase 3 trial will support the strong efficacy data seen in the LINKER-MM1 trial.
About the Author:
Karen Rodriguez Lorenc, M.D.
Vice President, Therapeutic Area Lead, Hematology Oncology within the Hematology Clinical Development Unit, Regeneron
Karen is responsible for the overall strategic program direction for Regeneron’s hematology-oncology assets across all indications and phases of drug development. She has nearly two decades of clinical development experience, a deep understanding of end-to-end drug development, and a proven track record of success.
Beyond effectively leading cross-functional teams in a complex and dynamic environment, Karen is known for her scientific excellence, leadership, strong commitment to talent development, and collaborative spirit. As a medical oncologist by training, she refused to accept that relapsing or progressing patients eventually run out of approved therapies for their cancer.
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