Celgene expects its inflammation and immunology drugs to become big growth drivers in the coming years. One of these, the Crohn’s disease candidate mongersen, faces a data readout soon that could determine whether it was worth its hefty price tag – something that is still in doubt.
Celgene acquired mongersen, also known as GED-0301, for $710m up front from Nogra Pharma on the back of impressive phase II data. But there is some doubt about whether the high response rate was a true reflection of the project's efficacy or was down to confounding factors. The new data, from a phase II endoscopy trial, could help answer these questions, and a positive outcome is far from assured.
The 63-patient study, requested by the FDA, will measure patients’ baseline disease using endoscopy, which visualises the digestive tract to assess the ulcers that are characteristic of Crohn’s. It will then evaluate whether their disease improves after 12 weeks' treatment versus placebo, with a primary endpoint of change in the SES-CD, the simple endoscopic score for Crohn's disease.
|% of market cap||8%|
|Event type||Phase II trial results|
Celgene expects data in the third quarter, and plans to present them at a medical meeting in the second half. A contender could be United European Gastroenterology Week, being held on October 15-19 in Vienna; the company announced its previous phase II results at the same meeting in 2014 (Celgene Crohn’s focus turns to phase III, October 20, 2014).
That earlier study found remission rates of 55-65% with mongersen – above the 40-50% typically seen with anti-TNF biologicals. Mongersen also had a favourable safety profile and has the advantage of being oral, while TNF inhibitors are injected. This could help explain the bullish sellside consensus, which puts 2022 mongersen sales at $1.2bn.
Subjective vs objective
Several issues with the original phase II trial prompted scepticism. One is that remission was measured using the Crohn’s disease activity index (CDAI), a subjective patient-reported measure. In addition, patients were not screened at baseline using endoscopy, and many are believed to have mild disease, if they had Crohn’s at all.
The latest study could address these issues by using a more objective endpoint and confirming disease pathology at baseline.
Celgene will be looking for around a 25% improvement in SES-CD score after 12 weeks. This could then reach 50% at week 24, and endoscopic remission after a year, said Scott Smith, Celgene’s president of global inflammation and immunology, during the company’s second-quarter earnings call.
Leerink analysts, for one, are not convinced that data will live up to those from the previous trial – in July note they said they expected “tepid” results, forecasting remission rates of 20-30%. They pointed to a mixed biomarker response in the earlier study, writing: “It is difficult to conclude that mongersen is indeed modulating the disease as designed.”
Celgene has already forged ahead into phase III, but the primary endpoint of that study is the subjective CDAI. Mr Smith did not rule out amendments to the phase III trial.
Failure in the endoscopy study could call into more doubt the reliability of the subjective phase III endpoint and push mongersen, an antisense oligonucleotide, even further down the company’s list of priorities – it had already looked to be slipping down the pecking order with Celgene’s acquisition of Receptos and its multiple sclerosis/ulcerative colitis candidate ozanimod (Celgene strikes again with Receptos acquisition, July 15, 2015).
An unexpected trial win, meanwhile, would pave the way for a new drug class – there are no other Smad7-targeting products on the market or in late-stage development. After its setback with Revlimid in July, Celgene could do with some good news.
|CD-001||Phase II endoscopy trial||NCT02367183|
|CD-002||Phase III pivotal trial in Crohn’s disease||NCT02596893|