FDA Action Alert: Merck, Verona, AbbVie and Rocket

Pictured: A scientist with pill bottles in front o

Pictured: A scientist with pill bottles in front o

The FDA is facing four big target action dates in the final week of June, including one label expansion for a bispecific antibody and another for an investigational gene therapy.

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

To close out the month, the FDA will hand down decisions on four treatments, including one for an antibody-drug conjugate in lung cancer and another for a potential first-in-class treatment for chronic obstructive pulmonary disease.

Read below for more.

Merck, Daiichi Sankyo’s NSCLC ADC Awaits FDA Verdict

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

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

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

Patritumab deruxtecan elicited one complete response and the median duration of treatment response 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 assets include patritumab deruxtecan, as well as ifinatamab deruxtecan for small-cell lung cancer and raludotatug deruxtecan in ovarian cancer.

Verona’s COPD Drug Awaits Approval

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

Verona is supporting ensifentrine’s application, which was accepted in September 2023, with the Phase III ENHANCE trials, which demonstrated the drug candidate’s significant benefits on lung function and quality of life. According to a December 2022 readout from ENHANCE-1, ensifentrine cut the risk of exacerbations associated with COPD by 36% over 24 weeks versus placebo.

Designed for nebulized administration, ensifentrine is a dual inhibitor of the phosphodiesterase 3 and 4 enzymes, allowing the drug candidate to elicit 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 the NDA’s acceptance.

In anticipation of ensifentrine’s approval and launch, Verona has inked several financing contracts that could help it fund the product’s rollout. In January 2024, the biotech received a $400 million injection from Oxford Finance and Hercules Capital, while it secured another potential $650 million debt facility from Oaktree Capital Management in May 2024.

AbbVie, Genmab Seek Label Expansion for Epkinly

AbbVie and Genmab are proposing to use their bispecific antibody Epkinly (epcoritamab) to treat patients with relapsed or refractory follicular lymphoma (R/R FL). The FDA’s decision is due on June 28.

Designed using Genmab’s proprietary DuoBody platform, Epkinly is an intravenously administered IgG1-bispecific antibody that works by binding to both the CD3 protein on T cells and the CD20 protein on B cells. This mechanism of action allows Epkinly to facilitate the cytotoxic T cells to mount an immune response against CD20-positive B cells.

Epkinly won the FDA’s approval in May 2023 for the treatment for relapsed or refractory diffuse large B-cell lymphoma (DLBCL). It has not yet been cleared for any type of follicular lymphoma.

AbbVie and Genmab are supporting their bid for label expansion with data from the Phase I/II EPCORE NHL-1 trial, which showed that Epkinly could elicit high overall and complete response rates in R/R FL patients. In a readout presented in December 2023, Epkinly reached an overall response rate of 82% in R/R FL patients, with a complete response rate of 63% and a minimal residual disease negativity rate of 67%.

The FDA accepted Epkinly’s sBLA in February 2024 and granted it Priority Review.

Rocket Proposes Gene Therapy Kresladi for Rare Pediatric Disease

To close out the month, the FDA by June 30 will release its verdict on Rocket Pharmaceuticals’ BLA for Kresladi (marnetegragene autotemcel), an investigational gene therapy the New Jersey-based biotech is proposing as a treatment for severe leukocyte adhesion deficiency-1 (LAD-1).

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

In the absence of a successful bone marrow transplant, survival beyond childhood is rare. Patients that do make it to adulthood often experience recurrent severe infections, including pneumonia and septicemia.

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

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.