Irish biotech Prothena has decided to abandon a T helper (Th) cell-targeting drug after it failed to hit the mark in a phase 1b study in psoriasis—and despite earlier data indicating it could also be a treatment option for multiple sclerosis.
The PRX003 antibody—which targets the MCAM cell adhesion molecule (also known as CD146) on Th cells—was actually able to demonstrate it was having the desired biological effect in the 33-patient trial, but that didn’t translate into any “meaningful clinical benefit” for psoriasis patients, said the company.
The drug achieved near-complete downregulation of CD146 on the Th17 class of T cells, and partially blocked them from migrating into the skin, but the effect simply wasn’t strong enough to warrant taking the program into mid-stage testing, said Sarah Noonberg, M.D., Prothena’s chief medical officer.
“The clinical results in this study did not meet our pre-specified criteria for evidence of a well-defined relationship between biological activity and meaningful clinical effects,” she said, adding that the results “indicate the need for a deeper understanding of CD146 modulation in the treatment of complex disease states.”
Dublin-based Prothena previously reported a phase I study which demonstrated that PRX003 was able to neutralize MCAM, raising the hope it could be a treatment for inflammatory diseases in which multiple cytokines are thought to drive symptoms.
It’s a disappointment to the company, particularly in light of preclinical research a couple of years ago suggesting that inhibiting MCAM could be a new way to treat MS by blocking T cells from crossing the blood-brain barrier. Prothena had previously suggested that the drug could have potential in progressive MS, which is particularly resistant to current therapies.
Now, Prothena will maintain its focus on three remaining clinical-stage candidates. The trio is headed by NEOD001, in late-stage testing for the hematological disorder amyloid light-chain (AL) amyloidosis, and also includes Roche-partnered Parkinson's disease therapy PRX002 in phase 2 and PRX004, a candidate for rare disorder transthyretin-mediated amyloidosis (ATTR amyloidosis), which is expected to enter phase 1 next year.
Prothena’s CEO Gene Kinney, Ph. D., delivered a frank and pragmatic assessment of the disappointment. “As an organization guided by science and data-driven decision-making, we will only advance programs into mid- or late-stage clinical development that have the potential to offer clear and differentiated clinical benefits to patients.”