• Deciphera Pharmaceuticals’ ripretinib kept patients with advanced gastrointestinal stromal tumors (GIST) from progressing significantly longer than those on placebo, outperforming analyst expectations.
• The 6.3 month progression-free survival mark recorded by ripretinib in fourth-line patients appears to have outperformed that of rival avapritinib from Blueprint Medicines, which yielded a 3.7 month PFS in a similar population. The two agents have not been formally tested in a head-to-head trial, however, making direct comparisons more challenging.
• Deciphera shares rose by more than 80% Tuesday, adding more than $600 million to the biotech’s valuation.

Results from Deciphera’s so-called INVICTUS trial appear a best-case scenario, according to Piper Jaffray analyst Christopher Raymond. Not only does ripretinib compare favorably to competitors, but the data disclosed Tuesday suggests the drug could be more effective than established drugs in earlier lines of therapy, Raymond wrote.

INVICTUS tested ripretinib against placebo in GIST patients who have progressed after treatment with Gleevec (imatinib), then Sutent (sunitinib) and finally Stivarga (regorafenib). PFS was the primary endpoint, and with the data now in hand the Waltham, Mass.-based company expects to ask the Food and Drug Administration for approval in early 2020.

In this, Deciphera trails Blueprint, which submitted avapritinib for approval in June and expects an answer by Feb. 14, 2020. Despite its lead, news of the ripretinib data caused Blueprint shares to slump 4% Tuesday.

The only data that looked concerning was the objective response rate (ORR), a measure of tumor shrinkage or elimination. Just less than 10% of patients treated with ripretinib responded, a higher result than the 0% recorded in the placebo arm but not a statistically significant difference.

The FDA will look at PFS, Raymond notes, so a miss on ORR might not hurt Deciphera’s case.

Ripretinib and avapritinib are both kinase inhibitors, a type of drug that treats mutation-driven cancers, and both act on two targets, KIT and PDGFR-alpha.

The main differences between Deciphera’s INVICTUS trial and Blueprint’s Navigator trial was that Blueprint analyzed results in patients with a very specific mutation, PDGFR-alpha D842V mutant GIST. The Navigator study also did not have a placebo arm.

More important for ripretinib’s future is how well it performs in earlier treatment lines, such as the second-line setting in which Pfizer’s Sutent is usually used. A head-to-head trial, dubbed INTRIGUE, began in December 2018 and may read out in 2021.

Extrapolating from the results of the INVICTUS trial, SVB Leerink analyst Andrew Berens wrote today that ripretinib could achieve a PFS of 9.5 months in that population, a setting where Sutent has a PFS of less than six months.