Drugs

Agency Questions Confirmatory Study for Pepaxto

FDA reviewers say that a confirmatory trial has not confirmed the clinical benefit of Oncopeptides’ Pepaxto (melphalan flufenamide), which could jeopardize the continued marketing of the 2021 accelerated-approved drug for use in treating certain patients with relapsed or refractory multiple myeloma (RRMM). The agency’s Oncologic Drug Advisory Committee is being convened 9/22 to discuss efficacy and safety concerns arising from OCEAN, a confirmatory Phase 3 trial evaluating melphalan flufenamide with dexamethasone compared to pomalidomide (Bristol Myers Squibb’s Pomalyst) and to obtain input on Pepaxto’s benefit-risk.

In a briefing document released in advance of the meeting, the reviewers say OCEAN did not meet the prespecified primary endpoint — progression-free survival (PFS) superiority of melphalan flufenamide compared to pomalidomide. It dismisses the company’s revised PFS that showed a marginal PFS significance because it considered unconfirmed progression as events in the PFS analysis.

“The results of analyses of other efficacy endpoints such as ORR [objective response rate] and DOR [duration of response] were either not statistically significant or provided for a magnitude of effect that would not be considered clinically meaningful, the agency continues. “The results from the OCEAN trial demonstrated a detriment in overall survival for the melphalan flufenamide arm. The safety data indicate that the worse OS [overall survival] results are indicative of a safety concern and suggest a potential for harm with melphalan flufenamide.”

Additionally, the document criticizes the company’s post hoc subgroup exploratory analysis and modeling, which the agency says cannot be used to support a conclusion of a positive benefit-risk for Pepaxto when the “overall results show a detriment or unconfirmed benefit… The decreased OS, and the higher rates of toxicities in the melphalan flufenamide arm negate the marginal treatment effect on PFS observed with melphalan flufenamide. The concerning safety results noted in the OCEAN trial, the high rates of dose modification, and the inadequate dose exploration of the 40 mg flat dose prior to initiating the Phase 3 trial, indicate that the 40 mg flat dose is not optimized.”

The reviewers conclude that currently the overall available evidence indicates a “potential for harm, uncertain clinical benefit and suggests that the overall benefit-risk profile of melphalan flufenamide is unfavorable.”

Gupta Raises Concerns About Overton’s Independence, Ideology

FDA commissioner nominee Heidi Overton’s responses on vaccines, contraception and abortion medication during her 9/24 Senate confirmation hearing raise concerns that ideology could influence her decision-making if she takes over the agency, MSNBC senior medical analyst Dr. Vin Gupta said Friday. Gupta was particularly critical of Overton’

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FDA commissioner nominee Heidi Overton emerged from her Senate confirmation hearing Thursday (see earlier story) without resolving questions about whether she has enough Republican support to advance — and with a rapidly narrowing window for confirmation before the midterm elections. The Senate Health, Education, Labor and Pensions Committee hearing provided few

FDA Classifies Boston Scientific Imager II Catheter Recall as Class I

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FDA Approves Gazyva for Childhood-Onset Idiopathic Nephrotic Syndrome

FDA has approved Roche’s Gazyva (obinutuzumab) for reducing the risk of relapse in adults and children aged 2 and older with frequently relapsing or steroid-dependent, childhood-onset idiopathic nephrotic syndrome who are in remission. The expanded approval covers the use of the CD20-directed antibody beyond its existing

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Gupta Raises Concerns About Overton’s Independence, Ideology

Overton Confirmation Remains Uncertain After Senate Hearing

FDA Classifies Boston Scientific Imager II Catheter Recall as Class I

FDA Approves Gazyva for Childhood-Onset Idiopathic Nephrotic Syndrome