Prothena is cutting its losses on one of its key drug development programs after concluding their therapy failed to pass muster in a Phase Ib study of psoriasis.
PRX003 hit its mark — CD146 — on Th17 cells, as they expected. But researchers didn’t see the kind of pharmacodynamic effect they were looking for. So there will be no Phase II to come in either psoriasis or atopic dermatitis, two ailments which have seen considerable progress recently from newly approved therapies.
To their credit, execs at Dublin-based Prothena $PRTA were unsentimental in their evaluation of the results. And for a small study with 33 patients divided between a variety of doses and a placebo arm, Prothena gathered considerable knowledge from the study.
The biotech’s stock dipped 6% on the news in after-market trading.
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Across all PRX003 dose levels in the Phase 1b MAD study, no clinically relevant or statistically significant benefit on PASI 75 response was observed. At week 12, 29 percent of PRX003-treated patients (2 out of 7) in the 1 mg/kg dose cohort achieved a PASI 75 response (p=0.2 relative to placebo), and no patients in the 3 mg/kg, 10 mg/kg or 30 mg/kg dose cohorts achieved a PASI 75 response. Evaluation of Th17 cell migration revealed insufficient decreases in Th17 cell infiltration into tissue. Additionally, as measured from skin biopsies there were no clinically meaningful or dose-dependent changes in RNA transcript levels of genes associated with Th17-mediated inflammation, including IL-17A, IL-17F, IL-6, TNFα, and IFNγ. Despite modest evidence of a clinical effect on PASI 75 response at the lowest dose level, there was no relationship between dose levels, RNA transcript levels or other markers of inflammatory activity that provided evidence of a meaningful therapeutic effect. Collectively, these data demonstrated that near-complete downregulation of CD146 is insufficient to inhibit Th17 cell infiltration and associated inflammation to the degree necessary to achieve meaningful clinical benefit in patients with psoriasis.
CEO Gene Kinney says the focus now is on NEOD001 (Phase IIb and Phase III), PRX002 (Phase I) and PRX004 (expected to enter Phase I by mid-2018).
“While we observed occupancy and downregulation of CD146 following administration of PRX003 consistent with our previous Phase 1a SAD study, 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 required to advance PRX003 into mid-stage clinical development for psoriasis or psoriatic arthritis as previously planned,” said Sarah Noonberg, chief medical officer of Prothena. “Moreover, these results indicate the need for a deeper understanding of CD146 modulation in the treatment of complex disease states. We want to thank the patients, clinicians and site coordinators who have helped us execute this thorough study.”
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