Exciting FDA Developments: GSK and Alnylam Await a Momentous Decision

This week promises high-stakes decisions in the world of pharmaceuticals, with GSK eagerly anticipating the fate of its myelofibrosis breakthrough, momelotinib. Meanwhile, Alnylam is set to make a compelling case for patisiran as a potential game-changer in the treatment of cardiomyopathy linked to ATTR amyloidosis. Stay tuned for groundbreaking developments!

Alnylam Looks to Make Patisiran’s Case in Second Indication

On September 13, the FDA is set to embark on a crucial deliberation as its Cardiovascular and Renal Drugs Advisory Committee convenes. The topic of discussion: Alnylam’s bold bid with a supplemental New Drug Application (sNDA) for Onpattro (patisiran) aimed at adults grappling with the challenging realm of cardiomyopathy in wild-type or hereditary transthyretin-mediated (ATTR) amyloidosis. The much-anticipated FDA verdict is slated for October 8.

ATTR amyloidosis, a rare and relentless ailment, manifests when misfolded transthyretin proteins form amyloid fibrils that wreak havoc in various organs, including the nerves, gastrointestinal tract, and the heart itself. In the heart, these amyloid clusters stiffen the walls and impede their pumping prowess.

Alnylam’s visionary application, accepted by the FDA in February 2023, seeks to harness the potential of patisiran to combat cardiomyopathy triggered by the nefarious buildup of transthyretin in the heart. This audacious move is supported by compelling data from the Phase III APOLLO-B trial. This trial, a randomized, placebo-controlled, and double-blinded endeavor, unveiled the promising prospect of enhancing patients’ quality of life and functional capacity through patisiran treatment.

Crucially, patisiran demonstrated a commendable safety profile in the challenging terrain of ATTR-cardiomyopathy. Most side effects encountered were mild to moderate in severity, and the overall adverse event landscape aligned with findings from previous clinical studies.

Patisiran, marketed as Onpattro in the U.S. for polyneuropathy linked to hereditary ATTR amyloidosis, is an injectable double-stranded siRNA therapeutic. Its ingenious mechanism involves binding to messenger RNA encoding transthyretin, effectively tagging it for destruction. This orchestrated destruction results in a marked reduction in the overall level of this problematic protein in the body.

This groundbreaking mechanism of action earned Onpattro its stripes back in August 2018 when the FDA granted it approval for hereditary ATTR amyloidosis polyneuropathy, marking a historic milestone as the first-ever RNA interference therapeutic to secure the regulator’s coveted authorization.

GSK Awaits Momelotinib Verdict in Myelofibrosis After Delay

Anticipation is mounting as the FDA’s decision on GSK’s New Drug Application (NDA) for momelotinib, a potential breakthrough treatment for myelofibrosis patients with anemia, is set to be unveiled by September 16. This highly-anticipated decision follows a three-month delay to scrutinize fresh data.

Momelotinib, an investigational medication, boasts a ‘novel mechanism of action’ that takes aim at three critical signaling pathways: JAK1 and JAK2, as well as the activin receptor type I (ACVR1) cascade—a strategic approach to tackling the complexities of myelofibrosis, as highlighted in GSK’s press release explaining the delay. Originating from California biotech Sierra Oncology, which GSK acquired for a hefty $1.9 billion in April 2022, momelotinib has garnered attention for its potential to revolutionize treatment.

By effectively silencing the JAK1 and JAK2 pathways, momelotinib offers relief from the burden of splenomegaly and ushers in improvements in patients’ overall well-being. Its multifaceted action on the ACVR1 cascade may also hold the key to reducing levels of the hepcidin protein, a notorious culprit in myelofibrosis-associated anemia.

The journey to FDA consideration began in August 2022 when GSK’s NDA was first accepted. An initial target action date of June 16, 2023, was set. However, on the brink of the deadline, the FDA announced a three-month extension to evaluate compelling new data, further intensifying the anticipation surrounding momelotinib.

GSK supported its regulatory bid for momelotinib with robust data from the Phase III MOMENTUM trial. This pivotal study showcased momelotinib’s prowess by meeting its primary efficacy endpoint—achieving a reduction of at least 50% in the Total Symptom Score after 24 weeks of treatment.

Impressively, momelotinib also excelled in secondary efficacy metrics, including transfusion independence and splenic response rate. These groundbreaking findings were presented at the 64th American Society of Hematology (ASH) Annual Meeting in December 2022, setting the stage for a potential game-changer in myelofibrosis treatment.

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