Experimental lupus therapy only shows significant effect at highest dose

Reuters Health - 16/03/2022 - Up to 54% of patients with systemic lupus erythematosus (SLE) were helped by daily therapy with Bristol Myers Squibb's experimental drug iberdomide, but only at the highest dose tested, researchers report in Thursday's New England Journal of Medicine.

The phase 2 study of 288 volunteers rated benefit based on a 105-point scale that assessed lupus activity. A 4-point drop during the 24-week treatment period was considered improvement.

That was achieved by 54% of the 81 patients given a 0.45 mg dose, 40% of the 82 who received 0.30 mg daily, 48% of 42 treated with 0.15 mg, and 35% of the 83 given placebo.

Only the difference between placebo and the highest dose was significant (P=0.01).

The new results are "potentially exciting," Dr. Karen Costenbader of Brigham and Women's Hospital in Boston writes in an accompanying editorial. But, she cautions that "there have been too many phase 3 trial failures" for potential SLE treatments, and notes that the highest dose of the iberdomide "squeaked by" with a positive result.

Lead study author Dr. Joan Merrill echoed that concern, characterizing the results as "promising" but noting that secondary endpoints were not met.

"I really think we need more study of this drug," she said.

The drug company paid for the study, and the results were revealed in September at the American College of Rheumatology Convergence 2021 virtual meeting.

During that session, Dr. Merrill, a member in the arthritis and clinical immunology program of the Oklahoma Medical Research Foundation, reported that 214 patients had completed 52 weeks of follow-up after 72 placebo patients had been switched to the two highest doses. Response rates increased to 60% for the 0.30 mg dose and 58% for the 0.45 mg dose.

Lupus affects an estimated 161,000 to 322,000 people in the U.S. The autoimmune disease is notoriously difficult to study, in part because "the disease is always different in different people," background medications can skew results and the severity of the disease is not always scored consistently, Dr. Merrill said.

This trial, conducted at 117 sites around the world, involved people with active, moderate-to-severe SLE.

The rate of adverse events was 78% with the two highest doses of the drug versus 65% with placebo. Serious or severe side effects seemed to be similar between placebo and iberdomide recipients, but those receiving the drug appeared more prone to urinary tract and upper respiratory tract infections, neutropenia and leukopenia.

"The several red flags in this trial, including a high incidence of adverse events and treatment discontinuation, the fact that secondary endpoints (including one for cutaneous lupus) were not met, small effect sizes, and the potential teratogenicity and thrombogenicity of iberdomide," temper enthusiasm for the new results, Dr. Costenbader said.

But Dr. Merrill expressed some optimism because the data may hint at new avenues to pursue. For example, iberdomide seemed to be more effective in patients with a high Type I interferon gene signature.

"Maybe we should look at this more," she said. "There are clues in this paper that we might be able to find a subset of these patients where it might be more effective."

SOURCE: https://bit.ly/36dXRwj and https://bit.ly/3KBdL2P The New England Journal of Medicine, online March 16, 2022.

By Gene Emery



Posted on 16 March 20225 April 2022