FDA Action Alert: Amgen, Alnylam and BMS

FDA sign_iStock, JHVEPhoto

Pictured: FDA Headquarters/iStock, JHVEPhoto

Over the next two weeks, the FDA is due to release its verdicts on Alnylam’s Onpattro in cardiomyopathy of ATTR and Bristol Myers Squibb’s Opdivo in adjuvant melanoma. But first, the regulator will convene an advisory committee meeting to debate the merits of Amgen’s Lumakras in non-small cell lung cancer.

AdComm to Weigh Full Approval of Amgen’s Lumakras in NSCLC

On October 5, the FDA’s Oncologic Drugs Advisory Committee will meet to discuss Amgen’s supplemental New Drug Application (sNDA) seeking full approval of Lumakras (sotorasib) in non-small cell lung cancer (NSCLC).

Lumakras, an oral inhibitor of G12C-mutated KRAS, won the FDA’s accelerated approval for NSCLC in May 2021. The drug is indicated for patients with KRAS G12C-mutated locally advanced or metastatic disease as determined by an FDA-approved test, and for those who have undergone at least one prior line of systemic therapy.

Amgen has since generated more data to back Lumakras and support its bid for traditional approval. In September 2022, the company posted findings from the Phase III CodeBreaK 200 study showing that the KRAS inhibitor achieved a significantly better progression-free survival and overall response rate than docetaxel.

Meanwhile, overall survival (OS), a key secondary endpoint, was not significantly different between the Lumakras and docetaxel arms. CodeBreaK 200 was not powered to detect a statistical difference in OS, a spokesperson told BioSpace at the time.

The FDA’s panel of external experts will discuss findings from CodeBreaK 200 and determine whether Lumakras’ benefit/risk ratio supports full approval. The FDA’s verdict is due on or before December 24.

Amgen is also developing Lumakras in other solid tumor types, including colorectal cancer and small cell lung cancer.

Alnylam Seeks Onpattro’s Expansion to Cardiomyopathy of ATTR

The FDA will render a decision by October 8 regarding an sNDA submitted by Alnylam seeking to add a second indication for its siRNA therapeutic Onpattro (patisiran).

Alnylam won its first approval for Onpattro in August 2018 in polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis. ATTR amyloidosis is a rare and progressive disease characterized by the build-up of misfolded transthyretin in various organs, including the nerves, that lead to their dysfunction. These proteins can also accumulate in the heart, stiffening its walls and compromising its pumping function.

Alnylam’s sNDA, which the FDA accepted in February 2023, proposes patisiran as a treatment for ATTR amyloidosis with cardiomyopathy. The application includes data from the Phase III APOLLO-B trial, which demonstrated that patisiran improved quality of life and functional capacity in patients with ATTR-cardiomyopathy.

The study also found patisiran to be safe, with most side effects being mild or moderate in severity. Adverse events were consistent with what had been established in previous studies.

In September 2023, the FDA’s Cardiovascular and Renal Drugs Advisory Committee voted 9–3 in favor of Alnylam, finding that the company’s data show a favorable benefit-risk profile for patisiran in this indication. The regulator is not bound by the advisory committee’s findings, though it often follows its advice.

Onpattro, an injectable double-stranded siRNA therapeutic, works by binding to the mRNA molecule that encodes transthyretin. This tags the mRNA for destruction, resulting in overall lower levels of the protein.

BMS Bids to Bring Opdivo to an Earlier Melanoma Setting

On or before October 13, the FDA will release its decision regarding Bristol Myers Squibb’s supplemental Biologics License Application (sBLA) proposing Opdivo (nivolumab) as an adjuvant monotherapy in patients with completely resected stage IIB or IIC melanoma.

Opdivo is already indicated for melanoma, for which it earned its first approval in December 2014. With the sBLA currently under review, BMS seeks to push into an earlier indication.

“Patients with stage IIB or IIC melanoma tend to be at high risk of disease recurrence,” Gina Fusaro, vice president and development program lead at BMS, said in a statement alongside the FDA’s acceptance of the sBLA. “Approximately one-third of stage IIB and half of stage IIC patients experience recurrence within five years after surgery.”

BMS is backing its application with data from the Phase III CheckMate -76K trial, which showed Opdivo reduced the risk of recurrence or death compared to placebo by 58% in patients with stage IIB or IIC disease. Recurrence-free survival over 12 months was also higher among Opdivo-treated patients.

As for safety, CheckMate -76K did not detect new signals of concern and Opdivo’s adverse event profile was consistent with that in previous studies.

Opdivo is approved for several other cancers, including NSCLC, head and neck squamous cell carcinoma, esophageal cancer, hepatocellular carcinoma and renal cell carcinoma. BMS is continuing to study the therapeutic potential of Opdivo, alone or in combination with other treatments, in earlier disease stages.

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

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