Merck KGaA’s $70 million bet on a treatment for a rare, locally aggressive cancer has delivered a phase 3 win. The tenosynovial giant cell tumor (TGCT) trial hit its primary endpoint, teeing up an option decision that could establish Merck as a global rival to Daiichi Sankyo and Ono Pharmaceutical in the indication.
The phase 3 trial tested CSF-1R inhibitor pimicotinib. Daiichi showed the mechanism can work in TGCT years ago, publishing phase 3 data in 2018 and winning FDA approval for Turalio the next year, but Merck identified a gap for another drug in the class. The German drugmaker paid Abbisko Therapeutics $70 million upfront for rights to pimicotinib in greater China and an option in the rest of the world last year.
Merck published phase 3 data on Tuesday. Investigators in China, Europe and North America randomized 94 people with TGCT to take pimicotinib or placebo. After 25 weeks of daily oral dosing, 54% of people on pimicotinib had responded, compared to 3.2% of their counterparts on placebo.
The result caused the study to hit its primary endpoint and suggests pimicotinib is competitive. Daiichi won approval for Turalio on the strength of a 120-patient study that reported response rates of 39% for the study drug and 0% for placebo at Week 25.
Merck reported statistically significant improvements in stiffness and pain. On the stiffness scale, Merck saw a 3.0 reduction in the pimicotinib group and a 0.57 dip in the placebo cohort. The figures for Turalio and placebo were 2.5 and 0.3, respectively, in Daiichi’s trial. More people on Turalio than placebo had a 30% or greater decrease in pain in Daiichi’s trial, but the difference fell short of statistical significance.
There were differences between the pimicotinib and Turalio trials that could confound comparisons of the data. Chinese sites enrolled almost half the patients in the pimicotinib trial. U.S. and Canadian sites enrolled 22% of the patients between them. The Turalio trial only activated sites in Australia, Europe and North America, and the U.S. dominated. Two-thirds of patients took pimicotinib, versus half for Turalio.
It is possible Merck will avoid a direct confrontation with Turalio. Daiichi’s drug is only approved in the U.S. As it stands, Merck only has the rights to pimicotinib in the Chinese mainland, Hong Kong, Macau and Taiwan. Deciphera Pharmaceuticals, a wholly owned subsidiary of Ono, has filed for approval of vimseltinib, another CSF-1R inhibitor, in the U.S. and Europe, but Merck could be first to market in China.
Merck is preparing to share the phase 3 data with regulators in China but is yet to say whether it will take up its option on pimicotinib in the rest of the world. Competition could be more intense in Europe and, in particular, the U.S. TGCT is rare, with an estimated global incidence of 43 cases per 1 million people, and the clear edge pimicotinib had in phase 1, when the response rate was 88%, eroded in phase 3.
Safety and tolerability is one area in which the challengers could differentiate themselves from Turalio. The FDA slapped a boxed warning on Turalio after Daiichi saw liver toxicity in phase 3. There was no evidence of cholestatic hepatotoxicity or drug-induced liver injury in the phase 3 vimseltinib trial.
Similarly, Merck reported no evidence of cholestatic hepatotoxicity in its phase 3 study. The drugmaker said pimicotinib was well tolerated. One patient stopped treatment after a treatment-emergent adverse event (TEAE). Five patients moved to a lower dose because of a TEAE.