Blueprint wins first FDA nod for a stomach cancer—though not exactly what it asked for

Blueprint Medicines has won its first FDA approval—for a targeted therapy that’s also the first for a particular kind of stomach cancer.

The FDA on Thursday greenlighted Blueprint’s Ayvakit, also known as avapritinib, for patients with rare gastrointestinal stromal tumor (GIST) carrying a platelet-derived growth factor receptor alpha (PDGFRα) exon 18 mutation. It's the drug's first step toward building a blockbuster-worthy list of targeted FDA approvals.

Ayvakit will launch within a week at the wholesale acquisition cost of $32,000 for a 30-day supply, regardless of dose strength, Blueprint’s chief commercial officer, Christina Rossi, said during a conference call Thursday. The company has gathered a commercial force of about 40 sales reps, she said.

The price was more than twice as much as SVB Leerink analyst Andrew Berens had initially expected. But in an investor note Friday, he acknowledged it as “justifiable” to treat the rare tumor, “where the drug has superlative efficacy and no competition."

Before Ayvakit, there was no drug specifically approved for GIST harboring that PDGFRα exon 18 mutation, which constitutes about 6% of all newly diagnosed GIST cases.

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Ayvakit proved its case to regulators with results from the Navigator study. In that phase 1 trial, Ayvakit shrank tumors in 84% of all 43 GIST patients, with 7% showing no sign of cancer after treatment. The numbers were even more impressive in patients with the most common form of D842V mutations, where Ayvakit shrank tumors in 89% of those 38 participants. A median duration of response was not reached.

In contrast, a retrospective study in 2012 found no evaluable D842V-mutated patients showed a response to Novartis’ TKI drug Gleevec (imatinib), which is FDA-approved to treat GIST.

Crossing the regulatory finish line with its first commercial product is definitely a milestone for Blueprint. But the nod isn’t as broad as the company had hoped, putting its plan to reach another subset of patients slightly behind rival Deciphera Pharmaceuticals.

When Blueprint submitted its new drug application back in June 2019, the goal was to get a go-ahead for both PDGFRα exon 18-mutant and fourth-line KIT-driven GIST. But in October, Blueprint unveiled that the FDA had decided to split those two indications.

Before granting that second approval, regulators want to see data from the phase 3 Voyager trial in fourth-line GIST, which is supposed to read out in the second quarter.

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Even though Ayvakit’s potential use in fourth-line GIST remains on an accelerated review path, the delay puts Blueprint slightly behind competitor Deciphera, whose ripretinib is under FDA real-time oncology review on the strength of a randomized progression-free survival win. By Jefferies analyst Eun Yang’s previous estimate, an FDA approval could come for Deciphera by year-end.

Meanwhile, both Ayvakit and ripretinib are eyeing expansions into second-line KIT-/PDGFRα-driven GIST. But Deciphera is ahead there, too, with the phase 3 Intrigue study already ongoing. As for Blueprint, it postponed starting its phase 3 Compass-2L trial to focus on completing the Voyager trial.

Overall, SVB Leerink’s Berens now estimates worldwide peak revenues of about $280 million for Ayvakit in PDGFRα GIST, about $640 million in KIT-driven GIST, and another $448 million in advanced systemic masotcytosis.