Roche’s chronic cough program has sputtered to a halt. The drugmaker, which axed the program after the drug candidate disappointed in phase 2, disclosed (PDF) the setback as part of a wider pullback from prospects that fell short of the bar for further development.
Genentech discovered the cough candidate, which goes by both RG6341 and GDC-6599, and took it into a phase 2 trial last year. The molecule is an antagonist of TRPA1, a calcium ion channel that researchers have linked to neuropathic pain and respiratory disease. After working around coagulation concerns, the team at Genentech hit upon a molecule it believed could become a first-in-class cough drug.
Those hopes failed to survive a key early test of clinical efficacy. A Roche spokesperson told Fierce Biotech “there were no clinically meaningful improvements in chronic cough or patient perceived cough severity” in a phase 2 trial. The molecule was well tolerated with no safety concerns, suggesting Genentech overcame the issues identified in toxicity studies, but the lack of efficacy overrode that positive outcome.
Roche’s decision eliminates a cough candidate that was differentiated from Merck & Co.’s once-rejected gefapixant and GSK’s phase 3 camlipixant, both of which target P2X3. RG6341 also had a different target than cough programs that are in midphase development at biotechs from China, Europe and the U.S.
The Swiss Big Pharma disclosed the removal of RG6341 from its pipeline as part of a third-quarter update that featured a clutch of other changes. Roche also axed a trial for divarasib, specifically a phase 2/3 trial that was comparing the KRAS G12C inhibitor to docetaxel in the second-line treatment of non-small cell lung cancer (NSCLC). But, at the same time, the company has started up another, separate, phase 3 trial in NSCLC.
Roche’s new NSCLC trial, which got underway last month, is comparing divarasib to Amgen’s Lumakras and Bristol Myers Squibb’s Krazati. The primary endpoint is looking at progression-free survival in people with KRAS G12C-positive advanced or metastatic NSCLC.
Speaking to Fierce Biotech during its third-quarter financial call Wednesday morning, the company said of the drug: "We do believe that divarasib [...] has the opportunity to be a best in class molecule. It's under investigation in a number of different settings, and we continue to think that it will be highly competitive in the market."
The pipeline update includes five other removals, all of which were previously disclosed. Roche revealed (PDF) it was axing four of the studies at its Pharma Day late last month. UCB broke the news of the fifth removal yesterday.
A spokesperson for Roche shared the thinking behind its changes. Roche culled its PD-1xLAG-3 bispecific tobemstomig after comparisons to historical and control data suggested the candidate was unlikely to “serve as a broad immune checkpoint inhibitor backbone to replace the current standard of care,” the spokesperson said.
Roche dropped a midphase hepatitis B program, which was testing RG7854, RG6346 and RG6084, and a phase 1 asset, RG6449, but the company is yet to give up on the indication. The spokesperson said Roche “continues to investigate the biological mechanisms underlying HBV disease and viral persistence in liver cells with the goal of identifying novel mechanisms to combat HBV infection.”
The other previously disclosed cull affected the GPRC5DxCD3 bispecific multiple myeloma candidate RG6234, also known as forimtamig. Roche removed the drug candidate from phase 1 after assessing “the evolving treatment landscape” and its focus on “transformative medicines that provide greater benefit to patients faster.”
The spokesperson’s statement on RG6234 echoes a comment Roche CEO Thomas Schinecker, Ph.D., made on a call with the media Wednesday. Schinecker said Roche has revalued its pipeline and defined five criteria that each molecule needs to meet to justify further development.
“With that, we have [removed] molecules where we didn't believe that they're going to make it, or the data was not differentiated enough, or the science was not there,” Schinecker said. “This opened the opportunity for us to actually do M&A deals and bring in other assets from the outside.”