Upcoming events – Rare disease data due from Chemocentryx and Sanofi

Chemocentryx and Sanofi are looking to target the complement pathway in ANCA-associated vasculitis and cold agglutinin disease respectively, with phase III data due in the fourth quarter.

Welcome to your weekly roundup of approaching clinical readouts. Chemocentryx is expected to report phase III results with its lead project, avacopan, in the fourth quarter. The drug inhibits the C5a receptor which is part of the complement system involved in inflammation; however, hopes are not high for this approach after the recent failure of Inflarx's similarly acting IFX-1.

Chemocentryx is taking aim at patients with antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV), a rare autoimmune disease where the complement pathway is overactivated, causing destruction of small blood vessels, which leads to organ damage and failure.

The current standard of care for AAV includes high dose steroids plus rituximab or cyclophosamide. However, these are not ideal, with steroids causing extensive immunosuppression; indeed over 50% of mortality within the first year of diagnosis is attributed to infection.

Chemocentryx’s trial, Advocate, has enrolled 331 patients  from the US, Europe and Japan. Rituximab or cyclophosphamide/azathioprine is given with either avacopan or the active comparator, the steroid prednisone at 60mg per day.

The trial has two primary endpoints; remission at 26 weeks and sustained remission at 52 weeks, assessed by the Birmingham vasculitis activity score (BVAS). Secondary endpoints include corticosteroid toxicity measures, quality of life and change in organ damage.

In Chemocentryx’s phase II Clear study two avacopan groups were tested and met non-inferiority versus placebo plus 60mg prednisone. The primary endpoint was ≥50% decrease of BVAS from baseline at week 12. Beyond the primary endpoint patients receiving avacopan also showed a significant improvement in health-related quality of life aspects and less cumulative organ damage compared to the standard of care group.

Avacopan's 2024 sales are expected to reach $268m, according to EvaluatePharma consensus. Vifor Pharma has rights outside the US. 

However, in June Chemocentryx suffered by association as Inflarx’s anti-C5a monoclonal antibody IFX-1 failed in hidradenitis suppurativa, a skin scarring condition. Inflarx’s shares plummeted 92% while Chemocentryx’s fell 20% on the news. Avacopan is currently in phase II in hidradenitis suppurativa. Advocate will need to be a hit if any confidence is to remain in targeting C5a or its receptor.

Trial

Results?

Trial ID

Phase III Advocate

Q4 2019 (note upcoming R&D day October 1)

NCT02994927

Phase II Clear

Proportion of patients with BVAS response at Week 12: avacopan plus 20mg prednisone (86%, p=0.002 vs. SOC), and avacopan plus no steroids (81%, p=0.01 vs. SOC) compared to the high-dose steroid containing SOC group (70%)

NCT01363388

SOC: standard of care

Also looking to target part of the complement pathway is Sanofi with sutimlimab, a monocolonal antibody hitting C1s. The project is being tested in cold agglutinin disease, a rare type of autoimmune haemolytic anaemia triggered by cold temperatures in which the body's immune system mistakenly attacks and destroys its own red blood cells.

Targeting the complement pathway is a novel approach. Current first-line therapy is B-cell-directed, including a rituximab-bendamustine combination, or rituximab monotherapy for those who cannot tolerate the former regimen. In cases of severe anaemia blood transfusions are given as a temporary measure.

Sanofi’s pivotal trial is called Cardinal. The open-label study includes 20 adult patients with haemoglobin levels <10g/dl, symptomatic disease and who have had one or more transfusion in the past six months. In part A patients received sutimlimab, which is given via intravenous infusion, for 26 weeks; part B involved a year of therapy.

The primary endpoint for part A is the percentage of patients with a response, defined as those who did not receive a blood transfusion or treatment for cold agglutinin disease; and who achieved a haemoglobin level of ≥12g/dl or whose haemoglobin increased ≥2g/dl from baseline. The primary measure for Part B is adverse events. Data are due in the fourth quarter.

A second phase III trial called Cadenza is ongoing, in patients without a prior history of blood transfusion, with a primary completion date of August 2020.

A small phase Ib trial showed a median increase in haemoglobin levels of 3.9g/dl within six weeks of treatment in seven out of 10 patients. In addition, six previously transfused patients became transfusion-free during treatment. The drug was well tolerated and there were no serious adverse events.

The project came to Sanofi through its acquisition of Bioverativ for $11.6bn last year, although that deal was focused on haemophilia therapies.

Sutimlimab sales are forecast to reach $164m in 2024, according to EvaluatePharma consensus; the drug, which has breakthrough therapy and orphan drug designation, has an NPV of $846m. 

Trial

Results?

Trial ID

Phase III Cardinal (patients with a history of blood transfusions)

 Q4 2019

NCT03347396

Phase III Cadenza (no prior history of blood transfusions)

 Primary completion August 2020

NCT03347422

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