Deucravacitinib and orelabrutinib perform well in early lupus trials

Early days for both agents

While both seem currently promising, it’s very early days for deucravacitinib and orelabrutinib as possible new agents for SLE.

Aside from SLE, deucravacitinib is being tested across multiple immune-mediated diseases. This includes psoriasis, where two phase 3 trials – POETYK PSO-1 and POETYK PSO-2 – have already been completed, and psoriatic arthritis, where a phase 2 trial has been reported; all with positive results.

Phase 3 testing of deucravacitinib will go ahead and recruitment may start toward the end of this year, but it’ll take years to complete the studies, Dr. Morand said. Even if the trials prove positive, neither agent is going to be available for clinical use for several years.

A case in point is anifrolumab (Saphnelo), which Dr. Morand was involved in assessing. Despite gaining approval in the United States and across much of the world, the drug still going through reimbursement processes.

“The trial data, and lots of post hoc analysis, show clearly that it’s a major step forward in treating lupus,” he said in an interview, but “access is limited in most places, so hands-on experience with that new treatment is still limited for most clinicians.”

As for all the other new targeted approaches under investigation, “although there’s a lot of trial activity, there’s still a couple of years away before any of the current trials deliver new treatment. That’s if they provide positive findings. Indeed, there have been numerous agents that have shown promise at phase 2 but then fall at the final phase 3 hurdle, including baricitinib, which Dr. Morand reported on in a separate poster presentation.

Phase 3 data proved disappointing: “Results are not sufficiently positive for that to go forward,” he said, adding that “transitioning from a successful phase 2 to a successful phase 3 is challenging, and many products have failed.”

Dr. Morand added: “It’s a very exciting time to be in lupus research, and there’s a lot of optimism about the future. But when I go back to my clinic tomorrow, I treat my patients exactly the same as I did last week and last year.”

It’s yet to be seen if deucravacitinib will fulfill its early promise, but it’s off to an impressive start. A positive for patients is that it’s an oral drug, with the potential to improve access to treatment across the world where getting infusions may be an issue.

“These are some of the most exciting data that I’ve seen at the phase 2 level in terms of effect size across all the readouts that are used,” Dr. Morand said. “There’s no guesswork here; it worked across all the measures. That’s very reassuring.”

The PAISLEY study was sponsored by Bristol-Myers Squibb. Dr. Morand has acted as a consultant to the company and received research support for the conduct of the trial. He disclosed acting as a consultant or receiving research funding from AbbVie, Amgen, AstraZeneca, Biogen, Eli Lilly, EMD Serono, Janssen, Genentech, Servier, Novartis, and UCB. Mr. Roy is the executive director of Lupus Therapeutics, which manages the Lupus Clinical Investigators Network based in North America. Lupus Therapeutics is the clinical trials arm of the Lupus Research Alliance, a nongovernmental, nonprofit funder of lupus research worldwide. The orelabrutinib study was sponsored by InnoCare Pharma. Dr. Li is the principal investigator for the trial but had no conflicts of interest to declare. Dr. Md Yusof disclosed receiving consultancy fees from Aurinia Pharmaceuticals.