Tuesday, September 4, 2018

Another setback for AstraZeneca as lupus drug fails phase 3 test


by Phil Taylor | Aug 31, 2018
Despite encouraging midstage data for AstraZeneca’s drug for systemic lupus erythematosus (SLE), anifrolumab has missed the target in the first of two ongoing phase 3 trials, putting its future in doubt.
The antibody, which binds to and inhibits the subunit 1 of the type I interferon receptor and is designed to dampen down the activity of inflammatory cytokines, was unable to achieve a significant reduction in disease activity compared to placebo over the one-year TULIP 1 trial.
AZ isn’t making a decision on its future just yet, as a second study—called TULIP 2—is still being run and is due to deliver results before the end of the year. However, the company’s terse statement on the disappointment suggests prospects are looking bleak.
autoimmune disease with significant unmet need among patients who struggle to achieve meaningful disease control,” said AstraZeneca Chief Medical Officer Sean Bohen. “The result of this trial is disappointing for patients and the lupus community.”
Anifrolumab is also in two midstage trials, one looking at a subcutaneous formulation and another zeroing in on kidney damage caused by lupus. If it turns out to be defunct, the failure strips out a big chunk of AZ’s clinical pipeline of drugs for autoimmune diseases, which is otherwise headed by phase 2 Sjogren’s syndrome candidate prezalumab, and leaves the company ever more dependent on its core respiratory, cardiovascular/metabolism and cancer assets.
TULIP 1 recruited adult patients with moderate-to-severe SLE who were given one of two doses of anifrolumab (150mg or 300mg) or placebo by intravenous infusion every four weeks. The design of TULIP 2 is very similar but is pitting only the 300mg dose against the control group.
For AstraZeneca, news of the disappointing data comes shortly after it announced another trial failure for MEK 1/2 inhibitor selumetinib in thyroid cancer after an earlier miss in non-small cell lung cancer, the termination of phase 3 trials for its Eli Lilly-partnered BACE inhibitor lanabecestat for Alzheimer’s disease, and setbacks for atopic dermatitis candidate tezepelumab and asthma drug tralokinumab.
It’s a big disappointment for AZ, which at one time was pitching anifrolumab as a potential rival to GlaxoSmithKline’s subcutaneous formulation of Benlysta (belimumab), an antibody approved for SLE in 2011 with sales of around $275 million in the first half of this year. The company previously said anifrolumab was a blockbuster prospect when the pharma giant was fighting off an unwelcome megamerger offer from Pfizer three years ago.
At the time, AZ CEO Pascal Soriot estimated that a combination of anifrolumab and another now-dropped candidate called sifalimumab could achieve $1 billion in annual revenue in SLE.

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