Roche's pipeline rethink hits 20% of new molecules as cancer candidates join discard pile

Roche has performed a little light spring cleaning, sweeping (PDF) a pair of phase 1 solid tumor drugs and an early-stage psychiatric disorder prospect out of the door as part of its update for the first quarter. The culls are part of a broader refocusing that has removed 20% of new molecules from the pipeline in recent quarters. 

The spring cancer clearout affected belvarafenib and RG6286. Belvarafenib, also known as RG6185 and HM95573, is an oral RAF kinase inhibitor that Roche’s Genentech licensed from Hanmi Pharmaceutical for $80 million upfront in 2016. The candidate was in phase 1 at the time of the deal. Hanmi began a phase 1b study to test belvarafenib in combination with either cobimetinib or cetuximab in 2017.

Hanmi, which retained the rights to the asset in South Korea, published data from the phase 1 trial and an expansion study in 2019 and continued to track patients in the phase 1b study to assess the effect of combining belvarafenib with a MEK or EGFR inhibitor. 

A Roche spokesperson said Genentech was “investigating belvarafenib in two clinical studies in various cancers” but has stopped enrollment in the trials and removed the asset from the portfolio. Genentech will continue to provide study treatment and monitor currently enrolled patients. 

The cut is part of a wider cull that has seen Roche terminate 20% of its new molecular entities since the third quarter of last year. Roche CEO Thomas Schinecker, Ph.D., said on a media call Wednesday that the cull has focused on assets that have a “lower likelihood” of success. The drugmaker needs to terminate some programs to free up cash to invest in accelerating “a number of projects that have a high likelihood to succeed and have a huge patient impact,” Schinecker said. 

Roche has split programs into three categories: highly promising prospects it wants to accelerate; assets that don’t warrant further investment because they are unlikely to be first or best in class; and molecules that need to generate more data to show whether they are a priority. Schinecker said the changes will continue in the second quarter, but the pipeline will settle down beyond that. 

The other newly culled oncology candidate, RG6286, is a bispecific antibody that binds to the colorectal cancer antigen LY6G6D and CD3 on T cells. Genentech began testing the candidate, which is also known as BLYG8824A, in colorectal cancer patients in 2020. The phase 1 clinical trial has an estimated primary completion date of early 2026.

Roche also used the update to confirm the removal of camonsertib, also known as RG6526, from phase 1. The Swiss drugmaker told Repare Therapeutics it is returning the rights to the synthetic lethal drug candidate in February, days after the dosing of a phase 2 patient and triggering a $40 million payment.

Finally, Roche removed one neuroscience candidate from its phase 1 pipeline and switched horses in an infectious disease. The neuroscience asset, RG6163, was in development psychiatric disorders, but Roche had said little publicly about the program. In complicated urinary tract infections, Roche dropped one LepB inhibitor, RG6319, and switched its focus to another molecule against the same target, RG6436.