Roivant ends longshot lupus program after phase 2 fail

Roivant’s CEO Matt Gline always knew the lupus drug brepocitinib was a longshot: “Anybody who is not afraid of a lupus study is an idiot, you shouldn’t trust them,” he told Fierce Biotech at the beginning of the year.

Now, it seems Gline’s fear was warranted. The therapy, snagged from Pfizer in 2022, did not lead to improvement in lupus disease activity at week 52, failing the main goal of a phase 2 study. Roivant’s Priovant unit will now drop the indication but continue with brepocitinib in a handful of other conditions including non-infectious uveitis (NIU).

Gline blamed the failure on high placebo response in the trial, according to a statement. Brepocitinib was tested in adult patients with moderate to severe active systemic lupus erythematosus. Efficacy was measured using a common scale for lupus called the Systemic Lupus Erythematosus Responder Index change of 4 (SRI-4).

“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,” Gline said in the Monday 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 formed the company Priovant around brepocitinib and another TYK2 inhibitor called PF-06826647, or ropsacitinib, last year in a deal with Pfizer. The Big Pharma holds a 25% stake in Priovant.

Priovant, which is keeping the specific data to itself for now, had hoped the phase 2 study would provide the data needed to seek an approval in lupus for brepocitinib.

Now, the company will turn to the rest of the brepocitinib program. The TYK2 inhibitor is being tested in a phase 2 trial for NIU with a readout expected in the first quarter of 2024. A phase 3 readout in dermatomyositis is expected sometime in 2025.

Roivant said that brepocitinib has also demonstrated potential benefit in six placebo-controlled mid-phase studies in psoriasis, psoriatic arthritis, alopecia areata, hidradenitis suppurativa, ulcerative colitis and Crohn’s disease.

Gline said today’s results show that brepocitinib “is a highly active agent with a good safety profile.”

Roivant is just the latest company to be stymied by lupus. Horizon Therapeutics, which was bought out by Amgen in October, suffered a phase 2 failure in July as well. Amgen also cut two of its own programs earlier this year, as did Eli Lilly.