The decision comes after the FDA put NUV-422, its candidate for high-grade gliomas, on a partial clinical hold, citing safety concerns.
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California-based biopharmaceutical company Nuvation Bio announced that it will discontinue the clinical development of NUV-422, its candidate for high-grade gliomas.
This decision comes shortly after the U.S. Food and Drug Administration put the candidate on a partial clinical hold, citing safety concerns. In a Phase I dose escalation study, several patients experienced eye redness, pain and blurred vision—all common signs of uveitis or eye inflammation. The partial hold paused further enrollment into the study, though patients who had already been given NUV-422 could continue taking it.
According to Nuvation, an internal risk-benefit assessment led to the decision to drop NUV-422. The company took into consideration an FDA request for a mitigation plan regarding the uveitis cases. Given that much is still unknown about the side effect and how it relates to NUV-422, Nuvation deemed that coming up with such a plan would be too difficult without further, extensive research.
NUV-422 was a cyclin-dependent kinase (CDK) 2/4/6 inhibitor, which hoped to improve upon the standard CDK 4/6 inhibitors by also acting through CDK2. The candidate was given the FDA’s Investigational New Drug (IND) clearance for various breast and prostate cancer forms in December 2021.
“Nuvation Bio was founded on a commitment to advance a broad pipeline of innovative therapies as quickly and safely as possible for people with cancers that do not currently have adequate treatment options. As part of this commitment, we have always operated as a scientifically rigorous, data-driven company,” David Hung, M.D., founder, president, and chief executive officer of Nuvation Bio, said in a statement. “Following an extensive analysis of the Phase 1 dose escalation study of NUV-422 in solid tumors, we made the determination that uveitis cannot be safely managed.”
Following the loss of one candidate, Nuvation now plans to redirect its resources and focus on the clinical development of NUV-868, it’s one remaining candidate. The company is also falling back on its novel small molecule drug-drug conjugate platform in hopes of identifying another potential clinical candidate. To bankroll these efforts, Nuvation is slashing its headcount by 35% and using its savings from discontinuing NUV-422. These cost-cutting measures should extend its cash runway through 2028.
NUV-868 is an oral, small molecule and highly selective inhibitor of the BD2 subunit of BET2 proteins. In particular, the candidate can inhibit BRD4, a member of the BET family of proteins that controls tumor growth and differentiation through epigenetic mechanisms. NUV-868 could also have synergistic activity with PARP inhibitors, leading to potentially better therapeutic efficacy against various solid tumors.
In January, the FDA cleared NUV-868’s IND application, and the company enrolled its first patient shortly after. The candidate is currently in Phase I study as a monotherapy against advanced solid tumors to assess its safety and determine its optimal dose.
There are also two ongoing preclinical assessments of NUV-868: One that looks at its combination with Olaparib as a treatment against ovarian, triple-negative, pancreatic and metastatic castration-resistant prostate cancers (mCRPC), and another that tests its combo with enzalutamide against mCRPC.
