Rare Daily Staff

ChemoCentryx and Vifor Fresenius Medical Care Renal Pharma reported positive late stage results from a trial of its experimental therapy avacopan for the treatment of patients with anti-neutrophil cytoplasmic antibody-associated vasculitis.

Anti-neutrophil cytoplasmic antibody-associated vasculitis (ANCA-associated vasculitis or ANCA vasculitis) refers to a group of rare systemic diseases in which over-activation of the complement pathway over-activates neutrophils, leading to inflammation and destruction of small blood vessels. This results in organ damage and failure, with the kidney as the major target, and is fatal if not treated. Current treatment for ANCA vasculitis consists of courses of non-specific immuno-suppressants (cyclophosphamide or rituximab), combined with high-dose long-term corticosteroid therapy that can be associated with significant clinical risk including death from infection.

The pivotal global study enrolled 331 patients with acute ANCA vasculitis who were randomized to receive avacopan plus non-specific immune-suppressants, or immune-suppressants plus high-dose corticosteroids. The study met both of its primary endpoints of disease remission at 26 weeks and sustained remission at 52 weeks, as assessed by the Birmingham Vasculitis Activity Score, or BVAS. Remission was defined as a BVAS score of zero and being off glucocorticoid treatment for ANCA vasculitis for at least the preceding four weeks.

BVAS remission at week 26 was achieved in 72.3 percent of the avacopan treated subjects versus 70.1 percent of subjects in the glucocorticoid standard-of-care control group. Sustained remission at 52 weeks was observed in 65.7 percnet of the avacopan treated subjects versus 54.9 percent in the glucocorticoid standard-of-care control group, achieving both non-inferiority and superiority to glucocorticoid standard of care.

Importantly, subjects who received avacopan experienced additional benefits compared to those in the glucocorticoid standard-of-care control group. These benefits, assessed as pre-specified secondary endpoints, included a significant reduction in glucocorticoid-related toxicity, significant improvement in kidney function in patients with renal disease, and improvements in health-related quality of life metrics.

Avacopan had an acceptable safety profile, with fewer subjects having serious adverse events in the avacopan group than in the glucocorticoid standard-of-care control group.

“These results exceed our expectations,” said Thomas Schall, president and CEO of ChemoCentryx. “Today we mark the dawn of a new and historic period in the lives of ANCA vasculitis patients. Until now ANCA vasculitis patients have had to endure regimens that contain chronic high doses of steroids and all their noxious effects, but with today’s data it is clear that the time of making patients sick with steroid therapy in an attempt to make their acute vasculitis better may at last be over.”

Shares of ChemoCentryx rocketed 250 percent on the news.

Based on the study results ChemoCentryx and VFMCRP plan to make regulatory submissions for full marketing approval to both the European Medicines Agency and the U.S. Food and Drug Administration in 2020.

Avacopan is an orally administered selective complement 5a receptor inhibitor that blocks the pro-inflammatory complement fragment known as C5aR while leaving the beneficial C5a pathway through the C5L2 receptor functioning normally. By precisely blocking the pro-inflammatory complement system on destructive inflammatory cells such as blood neutrophils, avacopan arrests the ability of those cells to do damage in response to C5a activation, which is known to be the driver of ANCA vasculitis.

Avacopan has Orphan Drug designation in the United States and the European Union.

ChemoCentryx discovered and is developing avacopan, and retains the commercial rights to the drug in the United States. It has granted VFMCRP an exclusive license to commercialize the drug in all countries outside the United States, with VFMCRP granting Kissei Pharmaceutical an exclusive sub-license to develop and commercialize the drug in Japan.

“This is the transformational result that clinicians and patients all over the world had been hoping for,” said David Jayne, director of the Vasculitis and Lupus Clinic, Addenbrooke’s Hospital, Cambridge. “The notable and significant improvements in quality of life, the reductions in overall glucocorticoid toxicities and especially the improvements in renal function with avacopan therapy when compared to the steroid-containing standard of care are remarkable. These each have direct impacts on the lives of ANCA vasculitis patients, with the renal function improvement having long-term implications on patient survival and kidney failure risk. In addition to changing the landscape of ANCA vasculitis therapy, these results have ramifications for other inflammatory diseases beyond ANCA vasculitis. Today is a wonderful day for the community of many thousands of patients each year who are diagnosed and living with this devastating disease.”

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