Potential drug therapies persist amid 'lupus trial graveyard'
SCOTTSDALE, Ariz. — Despite a series of recent clinical setbacks, the latest in “a very large and growing graveyard” for systemic lupus erythematosus research, Gregg J. Silverman, MD, professor of medicine and pathology at NYU School of Medicine, highlighted potential therapeutic candidates that have achieved early successes.
Following the announcement in August 2018 that anifrolumab (AstraZeneca) failed to achieve a statistically significant reduction in disease activity among patients with SLE, Silverman noted that the success of early phase trials can make researchers “overly optimistic” considering the track record for SLE trials.
In 2018, vobarilizumab (Ablynx) and rigerimod (Lupuzor, ImmuPharma) also failed to meet their primary endpoints in their respective phase 2 and phase 3 trials among patients with SLE. However, Silverman highlighted a pair of drugs showing promising phase 2 results: baricitinib (Olumiant, Incyte & Eli Lilly) and ustekinumab (Stelara, Janssen).
“The phase 2 extra-renal trial of baricitinib looks good; ustekinumab looks even better,” Silverman said.
Following phase 2 study results demonstrating that 4-mg doses of baricitinib were associated with significant clinical improvements among patients with SLE, the FDA granted fast track designation for the treatment of SLE in December 2018. Similarly, the phase 2 trial for ustekinumab demonstrated improved global and organ-specific SLE activity measures that were sustained through 1 year, with a safety profile consistent with the drug’s other indications.
“I’m optimistic for baricitinib because I’m really kind of a closet optimist. Ustekinumab is an unexpected success but I think it has a lot of potential,” Silverman said. He also noted promising findings from the ongoing phase 2 study of obinutuzumab (Gazyva, Genentech) for the treatment of lupus nephritis.
“This is really an exciting agent,” he said. “Obinutuzumab is actually an FDA-approved third-generation anti-CD20 for the treatment of [chronic lymphocytic leukemia]. We should know within the next 12 to 18 months whether this agent is secure.” – by Bob Stott
Silverman G. Translational Advances in SLE and Vasculitis. Presented at: Seventh Annual Basic and Clinical Immunology for the Busy Clinician; February 15-16, 2019; Scottsdale, Ariz.
Disclosure: Silverman reports he is a consultant for Lilly, Onyx, Pfizer, Quest and Roche and receives grant support from the American College of Rheumatology Research Foundation, the Lupus Research Institute and NIH.