FDA Action Alert: Merck, Sanofi/AstraZeneca and Eisai/Biogen

 The FDA has a couple of significant events scheduled this week, including a target action date for a cytomegalovirus prophylactic and two high-profile advisory committee meetings.

Merck Proposes Prevymis as a Safer CMV Prophylactic

On June 5, the FDA is expected to decide Merck’s supplemental New Drug Application (sNDA) for Prevymis (letermovir), an antiviral drug being proposed as a prophylactic option for cytomegalovirus (CMV) disease in high-risk adult kidney transplant recipients.

Prevymis is a first-in-class non-nucleotide inhibitor of CMV that targets the virus’s DNA terminase complex, thereby preventing its replication. The drug is already approved as a CMV prophylactic in the U.S. It is indicated for adult patients who are seropositive for the virus and have received an allogeneic hematopoietic stem cell transplant (HSCT).

Merck backed its sNDA, which the FDA accepted in February 2023 and granted its Priority Review designation, with data from a Phase III randomized and double-blinded trial. This study established that Prevymis’s efficacy was non-inferior to Genentech’s Valcyte (valganciclovir), the current standard of care to prevent CMV disease in kidney transplant recipients.

Meanwhile, Merck’s antiviral outperformed the current standard in terms of safety, leading to fewer treatment-related adverse events and study dropouts, according to a company press release. Leukopenia and neutropenia, common side effects in this indication, were 38% lower in the Prevymis group than in Valcyte comparators.

Serious drug-related toxicities arose in 1.4% of Prevymis-treated patients, as opposed to 5.1% of Valcyte recipients.

Concomitant with prophylactic CMV supplemental application, Merck submitted a second sNDA seeking to extend Prevymis use from 100 to 200 days in adults undergoing HSCT at risk of late CMV infections. The target action date for this second application is September 7.

FDA Convenes Panel for Sanofi and AstraZeneca’s RSV Antibody

The FDA will convene its Antimicrobial Drugs Advisory Committee (ADAC) on June 8 to discuss a Biologics License Application (BLA) submitted by AstraZeneca and Sanofi for nirsevimab, a monoclonal antibody inhibitor of the respiratory syncytial virus (RSV) F protein, in the pediatric setting.

The target action date for nirsevimab is in the third quarter of 2023.

Nirsevimab is an investigational, long-acting antibody that elicits passive immunity against RSV by targeting and blocking the part of the virus it uses to attach to its target cells. This mechanism of action allows nirsevimab to prevent RSV from infiltrating the host cells, thereby preventing infection at a cellular level.

The pharma partners are supporting nirsevimab’s BLA, which the regulator accepted in January 2023, with data from the Phase III MELODY and Phase II/III MEDLEY trials, along with findings from several Phase IIb studies.

Together, these studies showed that a single dose of nirsevimab could consistently achieve protection of around 80% against medically attended RSV. The investigational antibody also protected an all-infant population against RSV infection requiring emergency visits, hospitalizations, doctor visits, and overall medical care.

Sanofi and AstraZeneca also released data from the Phase IIIb HARMONIE trial in May. This large-scale European study showed that nirsevimab could reduce hospitalizations due to RSV-related lower respiratory tract disease (LRTD) by more than 83%, compared with no immunization in infants under 12 months.

Nirsevimab has previously won the FDA’s Breakthrough Therapy Designation.

Adcomm to Discuss Traditional Approval for Leqembi

Following its accelerated approval in January 2023, Eisai and Biogen’s Alzheimer’s antibody Leqembi (lecanemab) will face the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee on June 9 regarding potential traditional approval.

The companies are aiming for full approval based on data from the confirmatory Phase III Clarity-AD study. Eisai and Biogen submitted their supplemental Biologics License Application immediately after accelerated approval was granted.

Leqembi’s January approval was based on the findings of a Phase II study, which showed the therapeutic antibody could lower accumulated amyloid-beta plaques in the brain, a key disease biomarker.

Data from Clarity-AD also provided evidence of Leqembi’s clinical benefit, showing that the antibody could significantly slow clinical decline compared to placebo when measured using the Clinical Dementia Rating-Sum of Boxes (CDR-SB).

The FDA is set to decide whether to grant Leqembi full approval by July 6.

https://www.biospace.com/article/fda-action-alert-merck-sanofi-astrazeneca-and-eisai-biogen/