Blueprint challenges Novartis with new Ayvakit nod in blood disorders, with more competition to follow

With a new FDA approval. Blueprint Medicines' Ayvakit can now challenge Novartis' Rydapt in advanced systemic mastocytosis. (Blueprint Medicines)

After Ayvakit stumbled in gastrointestinal cancer, Blueprint Medicines pinned its hopes on an expansion into blood disorders to drive the drug toward blockbusterland.

Now, the company has snagged that FDA nod, where it will challenge Novartis’ Rydapt—though at least one analyst sees a door open to more competition.

Wednesday, the FDA approved Ayvakit for advanced systemic mastocytosis, a rare blood disorder.

 The new go-ahead adds to Ayvakit’s existing approval for certain PDGFRα-mutant gastrointestinal stromal tumors (GIST) and sets it up to compete with Novartis’ Rydapt, which got its own systemic mastocytosis go-ahead in 2017.

Ayvakit is now the first approved therapy to specifically target the KIT D816V mutation, which causes nearly all systemic mastocytosis (SM) cases, the company said.

Blueprint’s tagging Ayvakit with a 30-day list price of $33,568 for both systemic mastocytosis and GIST, a media aide to the company told Fierce Pharma.

The approval specifically covers aggressive systemic mastocytosis, SM with an associated hematological neoplasm, and mast cell leukemia.

Ayvakit proved its worth in the phase 1 Explorer trial and phase 2 Pathfinder trial. Among 53 evaluable patients who had a median follow-up of 11.6 months, Ayvakit triggered complete remission in 28% and reached partial remission in another 28%.

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But an update of the Pathfinder study at the recent American Association for Cancer Research leaves room for future competition, SVB Leerink analyst Andrew Berens said in a note in April.

At that meeting, Blueprint unveiled data showing 92% of responders had to reduce their Ayvakit dosing levels from 200 mg at the beginning of the trial to 100 mg or below because of side effects. Most of the patients who cut their doses suffered cytopenia, or a low number of blood cells.

A company exec told Berens that the dose could be dialed back up, but that many patients were still in remission at the lower dose. Because doctors constantly monitor advanced SM patients anyway, dosing adjustments shouldn’t be cumbersome, the exec explained, according to Berens.

However, Berens believes the dosing switches could spell a win for Cogent Biosciences’ bezuclastinib (CGT9486), which has shown lower rates of cytopenia in its GIST clinical trials compared with Ayvakit’s own GIST studies.

If the safety edge pans out in bezuclastinib's late-stage trial, the Cogent rival “could keep patients at a higher dose level for longer and potentially drive deeper, more durable responses,” Berens wrote in the note.

Cogent recently won FDA clearance to begin a pivotal phase 2 trial of bezuclastinib in advanced SM, and it plans to start a late-stage clinical trial for GIST patients later this year.

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Ayvakit’s future was previously clouded by a trial flop—and hence an FDA rejection—in a broader, heavily pretreated GIST population. But SM represents a larger opportunity for Blueprint.

An advanced SM label could mean $737 million in U.S. peak sales, Berens wrote in a separate note in April. And adding the EU market could make the indication a blockbuster opportunity for Ayvakit, Berens figured. By comparison, the SVB Leerink analyst only projected $307 million for the drug’s GIST use across the U.S. and EU. In the first quarter, Ayvakit generated $7 million in sales.

Meanwhile, Blueprint’s also testing Ayvakit for indolent SM in the phase 2 Pioneer trial, and it’s developing a follow-up KIT D816V inhibitor dubbed BLU-263.

Editor's Note: The story has been updated with the correct Ayvakit list price.