Celgene’s ‘oral Vidaza’ clears phase 3 leukaemia trial

Celgene’s oral version of acute myeloid leukaemia (AML) chemotherapy azacitidine has hit the target in a phase 3 trial, setting up regulatory filings in the first half of 2020.

The formulation – known as CC-486 – is an orally-active version of Vidaza, Celgene’s already-marketed azacitidine product which is administered intravenously. Vidaza was a big seller for Celgene in the past but has been hit by generic competition in the US and Europe in recent years.

The new QUAZAR AML-001 study compared CC-486 to placebo as a maintenance therapy for newly-diagnosed AML patients who had a complete response to first-line chemotherapy for the blood cancer, or a complete response with an incomplete blood recovery. Dosing was once-daily for 14 days of a 28-day cycle, with treatment continuing until disease relapse.

It showed a “highly statistically significant and clinically meaningful improvement in overall survival” compared to placebo, according to Celgene, as well as improving on the secondary measure of relapse-free survival.

At its height, Vidaza was bringing in upwards of $600m a year as a treatment for AML and myelodysplastic syndromes (MDS), but has been almost entirely supplanted by generics in the US market with sales falling to just $2m last year.

The product still brought in $136m in ex-US sales, but is likely to see another dramatic decline in 2019 and beyond as the first generics have now arrived in Europe.

CC-486 gives Celgene an opportunity to try to resurrect its azacitidine franchise, moving use of the drug beyond its usual use as first-line induction chemotherapy thanks to its oral dosing. It’s also testing the drug in MDS, non-Hodgkin’s lymphoma (NHL) and other cancers, both alone and in combination with checkpoint inhibitor drugs.

“AML remains a deadly blood cancer where most patients are not curable and less than 30% of patients survive five years,” said Celgene’s chief medical officer Jay Backstrom (pictured below).

Jay Backstrom

“The CC-486 QUAZAR AML-001 study is the first phase 3 trial to demonstrate that the addition of maintenance therapy has the potential to extend overall survival, in a broad population of patients with newly-diagnosed AML who have achieved remission with induction chemotherapy.”

If approved, the CC-486 will round out an AML franchise at Celgene that along with Vidaza also includes Agios-partnered Idhifa (enasidenib), a targeted second-line therapy for patients with IDH2-positive cancer cells.