Brepocitinib fails to show benefits beyond placebo in Phase 2 trial
Roivant, Priovant to test brepocitinib for autoimmune disorders other than SLE
Brepocitinib, an investigational oral therapy, failed to show any benefits beyond a placebo in a Phase 2 clinical trial that tested it in adults with moderate to severely active systemic lupus erythematosus (SLE).
As such, the trial failed to meet its primary objective, as assessed using the SLE Responder Index (SRI-4), a composite measure of disease activity, according to Roivant and Priovant Therapeutics, which are developing brepocitinib for other autoimmune disorders as well. Priovant expects to release study data at a future date.
“We saw some of the highest SRI-4 responder rates ever observed in a lupus study in the active arm of this trial, along with a favorable safety and tolerability profile,” Matt Gline, Roivant’s CEO, said in a company press release. “Unfortunately, we also saw the highest placebo response rate observed in any significant SLE study, and as such it was not possible to truly assess the impact of the drug, or to establish sufficient differentiation from other therapies in lupus patients.”
“Roivant and Priovant would like to extend our gratitude to the patients who participated in this trial, their caregivers, and the trial investigators that enabled this study and these insights,” he added.
SLE, also referred to as lupus, is the most common and serious form of lupus, which is marked by an abnormal inflammatory response against healthy tissues. The autoimmune disease can affect several tissues and organs, including the brain, lungs, skin, kidneys, and joints, resulting in a wide range of lupus symptoms.
Brepocitinib designed to block action of TYK2 and JAK1 enzymes
Brepocitinib is a first-in-class oral medication designed to block the action of two enzymes — TYK2 and JAK1 — that are involved in inflammation. This dual mechanism of action is expected to provide greater benefits against highly inflammatory autoimmune diseases than therapies that block either TYK2 or JAK1 alone.
The large, global Phase 2 study in SLE was designed to serve a registrational study, which is intended to provide sufficient data to support an application requesting brepocitinib’s approval. However, brepocitinib failed to show statistically significant benefits compared with a placebo after one year of treatment in people with moderate to severely active SLE.
In addition to lupus, brepocitinib is being tested as a treatment for several autoimmune and inflammatory disorders, including non-infectious uveitis (chronic eye inflammatory condition), dermatomyositis (rare disease that causes muscle weakness and skin rash), psoriasis (characterized by an itchy, scaly skin rash), psoriatic arthritis, alopecia areata (sudden hair loss), and inflammatory bowel disease.
Given its favorable safety and tolerability profile, clinically meaningful benefits observed in six previously completed Phase 2 studies, and performance in the lupus trial, the companies decided to continue developing brepocitinib for indications other than SLE.
“While we do not plan to progress the program in SLE, these results continue to support our view that oral brepocitinib is a highly active agent with a good safety profile,” Gline said. “We remain enthusiastic about brepocitinib’s ability to produce meaningful clinical benefit in non-infectious uveitis and dermatomyositis in Priovant’s ongoing trials, as well as in many other potential indications.”