FDA Updates for the Week of Feb 19: Cancer Approval Revoked

FDA Withdraws Approval of Pepaxto in Multiple Myeloma

The FDA has withdrawn the approval of Oncopeptides’ Pepaxto (melphalan flufenamide), which was approved for use in combination with dexamethasone to treat certain patients with multiple myeloma. The final decision was issued by FDA’s Center for Biologics Evaluation and Research Director Peter Marks, M.D., Ph.D.

Regulators indicated that the confirmatory study did not confirm Pepaxto’s clinical benefit, and the available evidence indicates Pepaxto is not safe or effective under its conditions of use.

Pepaxto had been granted accelerated approval in the United States on Feb. 26, 2021, but at the FDA’s request, Oncopeptides stopped marketing Pepaxto in the United States on Oct. 22, 2021.

Regulators in December 2022 requested that Oncopeptides voluntarily withdraw the indication for Pepaxto. The request is based on the outcome of the confirmatory phase 3 OCEAN study, which demonstrated an overall survival hazard ratio of 1.1 in the intent to treat population. A hazard ratio of more than 1 indicates a risk of harm.

This request came after the September 2022 meeting of the FDA’s Oncologic Drugs Advisory Committee (ODAC), which voted 14 to 2 against full approval. Regulators had indicated that the confirmatory trial (OCEAN) demonstrated a worse overall survival and failed to verify clinical benefit.

FDA Approves Amtagvi, the First TIL Therapy for a Solid Tumor

The FDA has granted accelerated approval for Amtagvi (lifileucel) to treat patients with advanced melanoma. Developed by Iovance Biotherapeutics, Amtagvi is the first approved tumor-infiltrating lymphocyte (TIL) therapy designed for patients with advanced melanoma who have experienced progression after previous treatment. It is indicated for those patients with unresectable or metastatic melanoma previously treated with a PD-1 blocking antibody, and if BRAF V600 mutation positive, a BRAF inhibitor with or without a MEK inhibitor.

Amtagvi is a one-time therapy intended that requires a patient’s cancer-fighting cells to be collected so they can be used to manufacture an individualized treatment. The wholesale acquisition cost of Amtagvi will be $515,000. Authorized treatment centers will administer Amtagvi to patients as part of a treatment regimen that includes lymphodepletion and a short course of high-dose Proleukin (aldesleukin), which is Iovance acquired in May 2023. Proleukin is used to treat patients with metastatic renal cell carcinoma and melanoma.

FDA Approves Biweekly Dosing of Tecvayli for Multiple Myeloma

The FDA has approved the supplemental biologics license application (sBLA) for Johnson & Johnson’s Tecvayli (teclistamab-cqyv) for a reduced dosing frequency every two weeks in patients with relapsed or refractory multiple myeloma (RRMM). This dosing regimen would be for patients who have achieved and maintained a complete response or better for a minimum of six months.

Tecvayli was granted accelerated approval in October 2022 to treat adult patients with relapsed or refractory multiple myeloma who received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody.

Tecvayli is a bispecific T-cell engager antibody to treat patients who have previously received four or more prior lines of therapy. When Tecvayli launched in November 2022, Tecvayli had a list price of $39,500 per month, based on the original dosing schedule.

The new approval is based on data from the phase 1/2 MajesTEC-1 study. At a median follow-up of 12.6 months after switching from every week dosing to either biweekly or monthly, 68.7% of patients remained in response for two or more years from the time of first response. As of data cut-off, 42 of 63 responders maintained a response after switching to less frequent dosing.

FDA Sets Date for First-in-Class Lung Cancer Therapy

The FDA has accepted the biological license application of datopotamab deruxtecan (Dato-DXd) to treat adult patients with locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) who have received prior systemic therapy. The Prescription Drug User Fee Act action date is during the fourth quarter of 2024.

Datopotamab deruxtecan is a TROP2-directed antibody drug conjugate (ADC) being jointly developed by AstraZeneca and Daiichi Sankyo. TROP2 is a protein that is expressed in the majority of non-small cell lung cancer tumors. There is currently no TROP2-directed antibody drug conjugate approved for the treatment of lung cancer.

The BLA is based on results from the pivotal TROPION-Lung01 phase 3 trial in which datopotamab deruxtecan reduced the risk of disease progression or death by 25% in overall population and by 37% in patients with non-squamous tumor. Datopotamab deruxtecan had demonstated improvement in progression-free survival (PFS) compared with docetaxel, the current standard of care, in patients with locally advanced or metastatic non-small cell lung cancer treated with at least one prior line of therapy.

FDA Sets Review Date for Linvoseltamab for Advanced Multiple Myeloma

The FDA has accepted for priority review the biologics license application (BLA) for linvoseltamab to treat adult patients with relapsed/refractory multiple myeloma that has progressed after at least three prior therapies. The FDA’s target action date is Aug. 22, 2024.

Developed by Regeneron, linvoseltamab is a bispecific antibody designed to bridge B-cell maturation antigen on multiple myeloma cells with CD3-expressing T cells.

The BLA is supported by data from a phase 1/2 trial. Results from this trial were released in December 2023. At a median duration of follow-up of 11 months where 117 patients received linvoseltamab 200 mg, the objective response rate was 71%, with 46% achieving a complete response or better.

A phase 3 confirmatory trial in patients with relapsed/refractory multiple myeloma is currently enrolling.

FDA Grants Priority Review to Dupixent in COPD

The FDA has accepted for priority review the supplemental biologics license application (sBLA) for Dupixent (dupilumab) as an add-on maintenance treatment in certain adult patients with uncontrolled chronic obstructive pulmonary disease (COPD). The target action date for the FDA decision is June 27, 2024.

If approved, this would be the sixth indication for Dupixent and the only biologic therapy for COPD. Dupixent is also approved to treat eosinophilic esophagitis, moderate-to-severe atopic dermatitis, moderate-to-severe asthma, chronic rhinosinusitis with nasal polyposis and the rare skin disease prurigo nodularis.

Dupixent, developed by Regeneron Pharmaceuticals and Sanofi, is a fully human monoclonal antibody that inhibits the signaling of the IL-4 and IL-13 pathways. The list price of Dupixent is $3,803.20 per carton.

The application for the COPD indication is based on data from two phase 3 trials evaluating the efficacy and safety of Dupixent in adults who were current or former smokers with uncontrolled COPD with evidence of type 2 inflammation. The primary endpoint was met in both trials, showing Dupixent reduced annualized moderate or severe acute COPD exacerbations by 30% in one trial and 34% in the second trial, compared with placebo. In both trials, Dupixent improved lung function compared with placebo, with improvements sustained at 52 weeks.