FDA Gives Baricitinib Fast Track Status for SLE Treatment

The U.S. Food and Drug Administration has granted fast track status to baricitinib for the treatment of systemic lupus erythematosus (SLE) patients, the treatment’s developers, Eli Lilly and Incyte, announced.

Fast track designation is intended to speed the therapy’s development and review for lupus patients, enabling more frequent communication with the FDA. Treatment candidates on this status also may benefit from accelerated approval and priority review.

“As part of the Fast Track designation, we will work closely with the FDA to further explore baricitinib’s potential as a treatment that can provide meaningful improvements for people with SLE,” Lotus Mallbris, MD, PhD, vice president of immunology development at Lilly, said in a press release.

Only one medication — Benlysta (belimumab) — has been approved to treat SLE in the past 50 years.

Baricitinib is already approved in the U.S., Europe, and Japan for rheumatoid arthritis, sold under the brand name Olumiant.

It is a selective inhibitor of JAK1 and JAK2 proteins, which decreases the production of inflammatory proteins and may prevent an inflammatory response. JAK activation is thought to increase the production of many proteins involved in SLE development, leading researchers to hypothesize that this oral inhibitor could have beneficial effects in SLE patients.

The treatment was therefore tested in a Phase 2 trial (NCT02708095), where 314 patients with active SLE and symptoms in the skin and joints were randomly assigned a placebo or one of two baricitinib doses — 2 mg and 4 mg.

The main goal was to determine if baricitinib, given orally once daily, could increase the proportion of patients whose symptoms of arthritis or skin rash were completely gone by 24 weeks, as defined by the Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K).

Secondary outcomes included the proportion of patients achieving a meaningful SLE response, along with changes from the start of the study in SLE disease scores.

Results from the trial, which led to the FDA’s decision, showed that more patients receiving the 4 mg baricitinib dose were clear of arthritis or rash at 24 weeks — 67%, compared with 58% of those on 2 mg baricitinib or 53% of those receiving a placebo.

However, patients receiving the active treatment were also more likely to experience side effects — 71% on the 2 mg dose and 73% on the 4 mg dose — compared with 65% of those on a placebo. The rate of serious adverse events was also two times higher among baricitinib-treated patients.

“The baricitinib 4 mg dose, but not the 2 mg dose, significantly improved the signs and symptoms of active systemic lupus erythematosus in patients who were not adequately controlled despite standard of care therapy, with a safety profile consistent with previous studies of baricitinib,” the researchers wrote in the study published in The Lancet earlier this year.

A Phase 3 trial — called BRAVE II (NCT03616964) — is already underway to study these two doses of baricitinib in SLE patients. The global study aims to recruit 750 patients across 136 locations to determine if more patients on the 4 mg baricitinib dose have a meaningful reduction in their lupus symptoms.

Additional goals include the percentage of patients achieving low disease activity, time to first severe flare, changes in steroid doses, changes in pain and fatigue scores, and reductions in number of tender and swollen joints. More information on how to enroll is available here.

“There has been only one new treatment for SLE approved in the U.S. in the past 50 years, and Lilly is excited to be at the forefront of potentially bringing a new treatment option to patients with this chronic, multi-organ autoimmune disease that can cause widespread tissue damage,” Mallbris said.