Merck’s ADC Pact With Daiichi Hits Regulatory Setback in FDA Rejection

 The FDA on Thursday rejected Merck and Daiichi Sankyo’s investigational antibody-drug conjugate patritumab deruxtecan, which the partners were proposing for the treatment of locally advanced or metastatic non-small cell lung cancer bearing certain genetic mutations.

In a complete response letter (CRL), the regulator cited issues with a third-party manufacturing facility but did not identify efficacy or safety problems with the application, according to the companies.

Ken Takeshita, global head of R&D at Daiichi Sankyo, in a statement said that the partners will “work closely with the FDA and the third-party manufacturer to address the feedback as quickly as possible.”

Patritumab deruxtecan was the centerpiece of the October 2023 deal between Merck and Daiichi Sankyo, which saw the pharma pay over $4 billion upfront and pledge around $18 billion in subsequent payments. In return, Merck gained the right to jointly develop and commercialize patritumab deruxtecan worldwide, except in Japan, where Daiichi Sankyo retained exclusive rights.

The deal also gave Merck access to two of Daiichi’s other antibody-drug conjugates (ADCs)—ifinatamab deruxtecan, a mid-stage candidate being assessed for extensive-stage small cell lung cancer, and raludotatug deruxtecan, which is being trialed in advanced ovarian cancer.

Designed and developed using Daiichi Sankyo’s proprietary DXd ADC platform, patritumab deruxtecan is an investigational candidate that works by targeting the HER3 protein, which is highly expressed across a wide variety of malignancies such as breast and lung cancer.

Once bound to its target, patritumab deruxtecan enters tumor cells and releases its toxic payload, an exatecan derivative topoisomerase I inhibitor, which triggers cell death. The FDA has previously granted the ADC its Breakthrough Therapy designation for locally advanced or metastatic non-small cell lung cancer (NSCLC) bearing EGFR mutations.

Merck and Daiichi Sankyo supported their Biologics License Application with data from HERTHENA-Lung01 study, a pivotal Phase II study that enrolled 225 patients who experienced disease progression after treatment with an EGFR tyrosine kinase inhibitor and platinum-based chemotherapy.

Results from HERTHENA-Lung01 showed an objective response rate of 29.8%, including one patient who achieved complete response and 66 patients who reached partial response. Nearly 65% of patients developed grade 3 or higher treatment-emergent adverse events, with 7.1% dropping out due to side effects. The study documented one fatal case of interstitial lung disease.

The FDA accepted patritumab deruxtecan’s application in December 2023 and granted it Priority Review status.

https://www.biospace.com/article/merck-s-adc-pact-with-daiichi-hits-regulatory-setback-with-fda-rejection/