FDA Action Alert: Amgen, Seagen/Astellas, Enzon/Sesen, BioMarin and Axsome .

The U.S. Food and Drug Administration (FDA) had a very packed calendar for this week, but almost everything on it was under a Priority Review pathway. All have either been approved, rejected or pushed back to a later date. Read on for more information.

Amgen’s Lumakras for Non-Small Cell Lung Cancer

Amgen had a target action date of August 16, 2021, for its New Drug Application (NDA) for Lumakras (sotorasib) for patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCL) after at least one previous systemic therapy. It was being considered under a Priority Review pathway. On May 28, the FDA approved the drug for this indication based on its overall response rate (ORR) and duration of response (DoR). Continued approval will be dependent upon verification and proof of clinical benefit in confirmatory trials.

The application was based on results from the Phase II CodeBreaK 100 trial. Sotorasib is a KRAS^G12C inhibitor and is being evaluated in 10 combinations with clinical sites around the world. NSCLC makes up 80% to 85% of all lung cancers, and 66% of patients have advanced or metastatic disease at the initial diagnosis. KRAS G12C is one of the most common driver mutations in NSCLC.

Seagen and Astellas’ Padcev for Urothelial Cancer .

Seagen and Astellas Pharma had a target action date of August 17 for their two supplemental Biologics License Application (sBLA) for Padcev (enfortumab vedotin-ejfv) for locally advanced or metastatic urothelial cancer. The applications were granted Priority Review and were evaluated under Project Orbis, which allows for concurrent submissions in participating countries. The first sBLA was built on the Phase III EV-301 trial, which hopes to shift the drug’s accelerated approval to regular approval. The second sBLA was based on the pivotal trial EV-201’s cohort 2, and was for an expansion of the current indication to include locally advanced or metastatic urothelial cancer patients who have been previously treated with a PD-1 or PD-L1 checkpoint inhibitor and are ineligible for cisplatin, a platinum-based chemotherapy.

On July 9, the FDA granted Padcev regular approval in the U.S. as well as for this new indication.

“With Padcev, for the first time, physicians can treat advanced urothelial cancer following treatment with a platinum-containing therapy and immunotherapy using an FDA-approved therapy that has demonstrated an overall survival benefit compared with chemotherapy,” said Andrew Krivoshik, senior vice president and Oncology Therapeutic Areas Head, Astellas.

Enzon and Sesen Bio’s Viceneum for Non-Muscle Invasive Bladder Cancer

Enzon Pharmaceuticals and Sesen Bio had a target action date of August 18 for its BLA for Viceneum for high-risk, BCG-unresponsible non-muscle invasive bladder cancer. It was being evaluated under a Priority Review pathway. The drug is a locally administered fusion protein made up of a recombinant fusion protein that targets epithelial cell adhesion molecule (EpCAM) antigens on the surface of cancer cells in order to deliver a protein payload, Pseudomonas Exotocin AA.

On August 13, the companies received a Complete Response Letter (CRL) from the FDA for the BLA. The FDA indicated it can’t approve the application in its current form and offered recommendations related to more clinical and statistical data and analyses as well as Chemistry, Manufacturing and Controls (CMC) issues associated with a recent pre-approval inspection and product quality.

“We are deeply disappointed by this unexpected result, and it is an unfortunate day for patients suffering from BCG-unresponsive NMIBC,” said Thomas Cannell, president and chief executive officer of Sesen. “We remain dedicated to our mission to save and improve the lives of patients by bringing new treatment options to patients, and we intend to work closely with the FDA to understand next steps.”

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