Positive Data Back Blueprint’s Bid for sNDA in Systemic Mastocytosis

FDA_Sarah Silbiger/Getty Images

Sarah Silbiger/Getty Images

Blueprint Medicines’ Ayvakit (avapritinib) is headed to the FDA for a new indication after the drug hit the mark in Part 2 of the PIONEER trial for non-advanced systemic mastocytosis (SM).

The data was strong enough that the company plans to submit a supplemental New Drug Application (sNDA) in the fourth quarter of this year, with a subsequent submission to the European Medicines Agency in 2023.

“Non-advanced systemic mastocytosis is a lifelong disease with severe physical, emotional and social impacts that profoundly reduce patients’ quality of life,” Lauren Denton, executive director of The Mast Cell Disease Society, said. “The PIONEER clinical trial results offer hope to these patients and help pave the way for new innovation in treatment.”

SM is a rare disease mostly driven by the KIT D816V mutation. It leads to uncontrolled proliferation and activation of mast cells, which causes chronic, severe symptoms across a spectrum. At its worst, it can lead to organ damage and poor survival.

The median overall survival in advanced SM (ASM) subtypes is 3.5 years, about two years in SM with an associated hematological neoplasm (SM-AHN) and less than six months in mast cell leukemia (MCL). Common debilitating symptoms affect the skin, gastrointestinal tract and neurocognition. Life-threatening anaphylaxis (allergic reactions) is also possible.

Ayvakit, a  kinase inhibitor, is engineered to selectively inhibit the D816V mutant KIT. The study evaluated Ayvakit plus best available care compared to placebo plus best available care. The primary endpoint was a highly significant difference in the mean change in total symptoms score (SS) at 24 weeks.

TSS was evaluated by the Indolent SM Symptom Assessment Form (ISM-SAF). The cohort receiving Ayvakit had a reduction of 15.6 points in mean TSS at 24 weeks, which continued to deepen to 20.2 points at 48 weeks in the patients who stayed on for the Part 3 open-label extension study. At 24 weeks, the control group had a decrease of 9.2 points in mean TSS.

The trial hit all key secondary endpoints, including significant improvements across all measures of mast cell burden. The drug was generally well-tolerated with a favorable safety profile.

“The PIONEER results showcase Blueprint Medicines’ dedication to advancing the promise of precision therapy for patients with significant medical needs,” Dr. Becker Hewes, M.D., chief medical officer at Blueprint, said in a statement. “Ayvakit has the potential to be the first approved medicine for non-advanced SM and the only treatment that would address the genetic root cause across advanced and non-advanced forms of the disease.”

Hewes called the news a “milestone” that “represents a watershed moment for the systemic mastocytosis community and Blueprint Medicines...” 

Ayvakit is approved by the FDA for adults with Advanced SM, including ASM, SM-AHN and MCL. It is also authorized to treat adults with unresectable or metastatic GI stromal tumor (GIST) harboring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations.

The data readout is good news and an additional catapult for Blueprint following major strategic financing announced in June. Blueprint cut deals with Sixth Street and Royalty Pharma totaling up to $1.25 billion. The funds will enable Blueprint to expand its pipeline and pursue business development opportunities, the company reported. 

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