The U.S. Food and Drug Administration (FDA) has granted Lynozyfic (linvoseltamab-gcpt) accelerated approval for adults with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor (PI), an immunomodulatory agent (IMiD) and an anti-CD38 monoclonal antibody.
Lynozyfic is a bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager.
This approval was based on study findings from the LINKER-MM1 trial, in which the overall response rate was 70%. Among those who responded, 89% still had a response at 9 months and 72% at 12 months, with a median follow-up of 11.3 months.
Glossary:
Overall response rate (ORR): percentage of patients whose cancer shrinks or disappears after treatment.
Cytokine release syndrome (CRS): an inflammatory response caused by immune cells releasing cytokines, which can cause fever, low blood pressure, and organ dysfunction.
Immune effector cell-associated neurotoxicity syndrome (ICANS): neurologic side effects including confusion, seizures, or difficulty speaking caused by immune cell therapies.
Risk Evaluation and Mitigation Strategy (REMS): a program required by the FDA to manage known or potential serious risks of a drug, restricting its distribution and use.
Life-threatening side effects, including cytokine release syndrome (CRS) and neurologic toxicity such as immune effector cell-associated neurotoxicity (ICANS), were reported in patients treated with Lynozyfic at the recommended dose in the LINKER-MM1 trial. CRS occurred in 46% of patients, with fewer than 1% experiencing it at grade 3 (severe) severity. Neurologic toxicity, including ICANS, occurred in 54% of patients, with grade 3 or 4 (life-threatening) events reported in 8%. These risks are reflected in a boxed warning in the prescribing information.
Given the risk of cytokine release syndrome and neurologic toxicity, including ICANS, Lynozyfic is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS), known as the Lynozyfic REMS. Additional warnings and precautions include infections, neutropenia, liver toxicity, and embryo-fetal toxicity.
The recommended intravenous dosing schedule for Lynozyfic begins with step-up doses of 5 milligrams, 25 milligrams, and 200 milligrams, followed by 200 milligrams once weekly for 10 doses, then 200 milligrams every two weeks. For patients who achieve and maintain a very good partial response or better at or after week 24 and have received at least 17 doses of 200 milligrams, the dosing can be reduced to 200 milligrams every four weeks.
In addition to priority review, linvoseltamab-gcpt has also received orphan drug designation and fast track designation — both of which are part of the FDA’s suite of expedited programs intended to help bring promising therapies to patients more quickly.
Orphan drug designation is granted to medications that treat rare diseases or conditions affecting fewer than 200,000 people in the United States. This designation provides incentives to drug developers, including tax credits for clinical testing, exemption from certain fees, and seven years of marketing exclusivity upon approval.
Fast track designation is designed to accelerate the development and review of drugs that treat serious conditions and fill an unmet medical need. This program facilitates more frequent communication with the FDA and allows the drug sponsor to submit sections of a new drug application as they are completed, rather than waiting until the entire application is ready.
These programs are outlined in the FDA’s Guidance for Industry: Expedited Programs for Serious Conditions — Drugs and Biologics, which provides direction to developers of therapies for patients facing life-threatening or debilitating diseases.
Reference
“FDA grants accelerated approval to linvoseltamab-gcpt for relapsed or refractory multiple myeloma” by U.S. Food and Drug Administration.
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