FDA on High Alert: Amgen, Alnylam, and BMS Await Regulatory Action

In the coming fortnight, the FDA is set to deliver critical decisions on several pivotal pharmaceuticals. Alnylam’s Onpattro for cardiomyopathy of ATTR and Bristol Myers Squibb’s Opdivo in adjuvant melanoma are among the high-stakes verdicts awaiting announcement.

However, before these verdicts are handed down, the FDA will gather experts for an advisory committee meeting to engage in a thorough discussion about the potential of Amgen’s Lumakras in the context of non-small cell lung cancer. The outcome of this meeting could profoundly influence the drug’s path forward.

Stay tuned as the FDA’s decisions shape the landscape of healthcare and patient treatment options in the days ahead.

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

Mark your calendars for October 5, when the FDA’s Oncologic Drugs Advisory Committee will assemble to deliberate over Amgen’s supplemental New Drug Application (sNDA) for Lumakras (sotorasib) in non-small cell lung cancer (NSCLC).

Lumakras, a remarkable oral inhibitor targeting G12C-mutated KRAS, received FDA’s accelerated approval for NSCLC back in May 2021. It’s a beacon of hope for patients with KRAS G12C-mutated locally advanced or metastatic disease, particularly those who have already undergone at least one prior line of systemic therapy, as determined by an FDA-approved test.

Since its accelerated approval, Amgen has been hard at work accumulating more data to bolster Lumakras’ candidacy for full and traditional approval. A significant milestone was reached in September 2022 when Amgen shared the findings from the Phase III CodeBreaK 200 study. These results underscored Lumakras’ superiority, showcasing significantly improved progression-free survival and overall response rates when compared to docetaxel.

However, the verdict on overall survival (OS), a pivotal secondary endpoint, didn’t yield a statistically significant difference between the Lumakras and docetaxel arms. It’s important to note that CodeBreaK 200 wasn’t specifically designed to detect a statistical divergence in OS, as clarified by a spokesperson at the time.

Now, the FDA’s esteemed panel of external experts is poised to examine the evidence from the CodeBreaK 200 study meticulously. Their primary objective is to assess whether Lumakras’ benefit-to-risk ratio aligns with the criteria for full approval. The pharmaceutical world eagerly awaits their conclusion, expected to be delivered on or before December 24.

But that’s not all—Amgen’s ambitions for Lumakras extend beyond NSCLC. The company is actively exploring its potential in various solid tumor types, including colorectal cancer and small cell lung cancer, ushering in an exciting era of oncological innovation.

Alnylam Seeks Onpattro’s Expansion to Cardiomyopathy of ATTR

The countdown is on, with the FDA set to deliver its verdict by October 8 on Alnylam’s supplemental New Drug Application (sNDA) for Onpattro (patisiran), a groundbreaking siRNA therapeutic.

Alnylam initially secured FDA approval for Onpattro in August 2018, marking a milestone in the treatment of polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis. This rare and progressive ailment is characterized by the accumulation of misfolded transthyretin in various organs, including nerves, leading to their dysfunction. The heart is not spared, as these proteins can stiffen its walls and compromise its pumping function.

The sNDA submitted by Alnylam aims to broaden the horizons of Onpattro, seeking approval for its use in ATTR amyloidosis with cardiomyopathy. The application relies on robust data from the Phase III APOLLO-B trial, which showcased patisiran’s remarkable ability to enhance the quality of life and functional capacity of patients grappling with ATTR-cardiomyopathy.

Moreover, the study uncovered a reassuring safety profile for patisiran, with most side effects falling into the mild to moderate range. Adverse events were consistent with previous findings from earlier studies.

Adding to the excitement, in September 2023, the FDA’s Cardiovascular and Renal Drugs Advisory Committee delivered a resounding vote of confidence, with a 9-3 verdict in favor of Alnylam. The committee found Alnylam’s data to support a highly favorable benefit-to-risk profile for patisiran in this new indication. While the FDA isn’t obligated to follow the advisory committee’s recommendations, it often aligns with their expert insights.

Onpattro, an injectable double-stranded siRNA therapeutic, operates by binding to the mRNA molecule responsible for encoding transthyretin. This action marks the mRNA for destruction, resulting in a reduction in overall protein levels—an ingenious approach to addressing the complexities of ATTR amyloidosis. The stage is set, and the medical world awaits the FDA’s decision with bated breath.

BMS Bids to Bring Opdivo to an Earlier Melanoma Setting

A pivotal decision from the FDA is on the horizon, expected to be unveiled by or before October 13. Bristol Myers Squibb’s supplemental Biologics License Application (sBLA) for Opdivo (nivolumab) is at the center of attention, with the proposal advocating for Opdivo as an adjuvant monotherapy for patients who have undergone complete resection of stage IIB or IIC melanoma.

Opdivo has already etched its mark in the realm of melanoma, securing its initial approval back in December 2014. With the sBLA currently under the FDA’s meticulous review, Bristol Myers Squibb is endeavoring to extend its reach into an even earlier stage of melanoma.

Gina Fusaro, the Vice President and Development Program Lead at BMS, highlighted the significance of this application, emphasizing that patients with stage IIB or IIC melanoma often grapple with a high risk of disease recurrence. She noted that approximately one-third of stage IIB and half of stage IIC patients experience recurrence within five years post-surgery.

Bristol Myers Squibb’s sBLA is fortified by compelling data from the Phase III CheckMate -76K trial. This pivotal study demonstrated that Opdivo wielded a powerful effect, reducing the risk of recurrence or death by a notable 58% when compared to a placebo in patients with stage IIB or IIC disease. Furthermore, Opdivo-treated patients exhibited a significantly higher rate of recurrence-free survival over a span of 12 months.

Crucially, the safety profile of Opdivo in the CheckMate -76K trial remained consistent with findings from earlier studies, with no alarming new signals detected.

Opdivo has established a formidable presence, securing approvals for several other cancers, including non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma, esophageal cancer, hepatocellular carcinoma, and renal cell carcinoma.

Bristol Myers Squibb continues to explore the vast therapeutic potential of Opdivo, both as a standalone treatment and in combination with other therapeutic modalities, across various stages of disease. The impending FDA decision holds the promise of broadening treatment options for patients battling melanoma at an earlier stage.

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