FDA Action Alert: Merck, Verona, AbbVie and Rocket

Pictured: A scientist with pill bottles in front of FDA headquarters/Taylor Tieden for BioSpace

By the end of the month, the FDA will announce decisions on four treatments, including one on an antibody-drug conjugate to treat lung cancer and another on a potential first-in-class drug to treat chronic obstructive pulmonary disease.

Read below to learn more.

Merck and Daiichi Sankyo’s NSCLC ADC awaits FDA ruling

By June 26, the FDA is expected to issue its opinion on Merck and Daiichi Sankyo’s Biologics License Application (BLA) seeking approval for the investigational antibody-drug conjugate (ADC) patritumab deruxtecan for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC).

Developed using Daiichi Sankyo’s proprietary DXd technology, patritumab deruxtecan is an investigational ADC targeting the HER3 protein, which is highly expressed in a variety of solid tumors, including breast and lung cancer. The ADC contains a number of exatecan derivative topoisomerase I payloads that can kill the targeted cancer cells.

Merck and Daiichi Sankyo’s BLA, which the FDA accepted and granted Priority Review in December 2023, is supported by data from the pivotal Phase II HERTHENA-Lung01 trial, which demonstrated an objective response rate of 29.8% in 225 patients with advanced or metastatic NSCLC whose disease had progressed after prior treatments.

Patritumab deruxtecan induced complete remission and the median duration of treatment success was 6.4 months.

Merck and Daiichi Sankyo entered into a global partnership in October 2023 to develop and commercialize three ADCs developed using Daiichi Sankyo’s DXd ADC platform. These compounds include patritumab deruxtecan and ifinatamab deruxtecan for small cell lung cancer and raludotatug deruxtecan for ovarian cancer.

Verona’s COPD drug awaits approval

Together with Merck and Daiichi Sankyo, the FDA is expected to decide on Verona Pharma’s New Drug Application (NDA) for ensifentrin for the maintenance treatment of chronic obstructive pulmonary disease (COPD) on June 26.

Verona supports the application for ensifentrine, accepted in September 2023, with the Phase III ENHANCE studies, which demonstrated the drug candidate’s significant benefits on lung function and quality of life. According to a December 2022 result from ENHANCE-1, ensifentrine reduced the risk of COPD-related exacerbations by 36% compared to placebo over 24 weeks.

Ensifentrine is designed for administration by nebulization and is a dual inhibitor of the enzymes phosphodiesterase 3 and 4, allowing the drug candidate to exert both anti-inflammatory and bronchodilator effects, according to Verona’s website. If approved, ensifentrine could represent the first novel mechanism for COPD treatment in more than a decade, according to Verona’s announcement of acceptance of the NDA.

In anticipation of the approval and launch of ensifentrine, Verona has entered into several financing agreements that could help it finance the product’s launch. In January 2024, the biotech company received a $400 million cash injection from Oxford Finance and Hercules Capital, while in May 2024 it secured another potential $650 million credit facility from Oaktree Capital Management.

AbbVie and Genmab seek label expansion for Epkinly

AbbVie and Genmab propose to use their bispecific antibody Epkinly (epcoritamab) to treat patients with relapsed or refractory follicular lymphoma (R/R FL). The FDA is expected to make its decision on June 28.

Developed using Genmab’s proprietary DuoBody platform, Epkinly is an intravenously administered bispecific IgG1 antibody that acts by binding to the CD3 protein on T cells and the CD20 protein on B cells. Through this mechanism of action, Epkinly can assist cytotoxic T cells in eliciting an immune response against CD20-positive B cells.

Epkinly received FDA approval in May 2023 for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL). It is not yet approved for any type of follicular lymphoma.

AbbVie and Genmab support their application for an extension of approval with data from the Phase I/II EPCORE NHL-1 study, which showed that Epkinly achieved high overall and complete response rates in patients with r./r. FL. In a study presented in December 2023, Epkinly achieved an overall response rate of 82%, a complete response rate of 63% and a minimal residual disease negativity rate of 67% in patients with r./r. FL.

The FDA accepted Epkinly’s sBLA in February 2024 and granted it priority review.

Rocket proposes Kresladi gene therapy for rare childhood disease

At the end of the month, the FDA will issue its opinion by June 30 on Rocket Pharmaceuticals’ BLA for Kresladi (marnetegragene autotemcel), an experimental gene therapy that the New Jersey-based biotech company is proposing to treat severe leukocyte adhesion deficiency-1 (LAD-1).

Severe LAD-1 is a rare pediatric disease caused by mutations in the ITGB2 Gene that encodes a crucial component of the CD18 protein. In healthy circumstances, CD18 helps leukocytes exit blood vessels to fight infections. In severe LAD-1 disease, which typically manifests in early childhood, patients suffer from recurrent and unresponsive bacterial and fungal infections.

Without a successful bone marrow transplant, survival beyond childhood is rare. Patients who reach adulthood often suffer from recurrent severe infections, including pneumonia and sepsis.

Kresladi addresses the underlying disease process of severe LAD-1 by delivering a functional copy of the ITGB2 gene and has FDA Regenerative Medicine Advanced Therapy, Rare Pediatric and Fast Track designations.

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Contact him on LinkedIn or email him at [email protected] or [email protected].