FDA approves Blueprint Medicines’ precision therapy for rare form of gastrointestinal cancer

In Clinical Studies News by Barbara Jacoby

By: Alaric DeArment

From: medcitynews.com

The Food and Drug Administration has approved the first ever drug for a rare subset of a type of gastrointestinal tract cancer.

The agency on Thursday afternoon approved Blueprint Medicines’ Ayvakit (avapritinib) for unresectable or metastatic gastrointestinal stromal tumors (GIST) harboring a PDGFRa exon 18 mutation in any line of therapy, making the drug the first precision therapy for GIST. PDGFRa exon 18 occurs in about 6% of cases of GIST, which is a type of genomically driven sarcoma, or connective tissue cancer accounting for 18% of sarcomas overall.

Shares of Blueprint were up less than 1% on the Nasdaq when markets closed Thursday.

“Ayvakit is the first of what we hope will be many approved medicines enabled by our research platform,” Blueprint CEO Jeff Albers said in a statement. “Now, as we begin to deliver Ayvakit to patients and their healthcare providers, we aim to fortify our leadership in the field of precision medicine and build a foundation for our broader portfolio by pairing our strong research and development capabilities with an equally talented commercial organization focused on addressing patient needs, accelerating diagnostic testing and enabling access.”

The approval was based on data from the Phase I NAVIGATOR study, in which patients with PDGFRa exon 18 mutations – including PDGFRa D842V-driven GIST – showed an overall response rate of 84%. Median duration of response was not reached.

Data presented at the American Society of Clinical Oncology in June also showed a 22% overall response rate among 111 patients with fourth-line GIST, including one complete response and 23 partial responses. The median duration of response was 10.2 months, with a 10.8-month median followup.

Blueprint submitted its approval application two weeks after ASCO, which the FDA accepted in August. However, the agency decided in October to split the company’s submission in two, with one for PDGFRa exon 18-mutated GIST and the other for fourth-line GIST. Ayvakit is an inhibitor both of PDFGRa and KIT, the latter of which is more commonly expressed in GIST. Novartis’ Gleevec (imatinib), now available as a generic, is a KIT inhibitor also approved and widely used to treat GIST.

Ayvakit’s approval represents a growing view of cancers not as tissue-specific diseases, but as genomically driven, which has led to the development of numerous drugs that treat them based on biomarkers rather than where they occur in the body. Bayer’s “tumor-agnostic” NTRK inhibitor Vitrakvi (larotrectinib), Pfizer’s Xalkori (crizotinib) for ALK fusion-positive non-small cell lung cancer, the label that Merck’s Keytruda (pembrolizumab) carries for MSI-H/dMMR solid tumors and Blueprint’s own investigational RET inhibitor pralsetinib are examples of drugs developed in this way.

Still, Frahm wrote that finding and testing patients will be the main challenge, given that PDGFRa testing is widely available, but hasn’t been widely adopted.

The list price of the drug will be $32,000 per month, regardless of dose level. Frahm noted that this was higher than the $17,000 his team had modeled.