Celgene's IBD Franchise Boosted by Otezla Ulcerative Colitis Success
Executive Summary
The big-selling psoriasis drug has achieved healthy clinical remission rates in a Phase II trial for ulcerative colitis, and Celgene believes Otezla and another potential blockbuster, ozanimod, will help it build a significant presence in inflammatory bowel disease.
Celgene Corp.'s hopes of becoming a force in inflammatory bowel disease have been helped by positive results from a mid-stage trial evaluating its psoriasis blockbuster Otezla (apremilast) for ulcerative colitis (UC).
The biotech major has advanced plans to initiate a Phase III program for Otezla 30 mg in UC on the back of data from a Phase II study presented at the European Crohn's and Colitis Organisation (ECCO) meeting in Vienna in patients who had failed at least one prior line of conventional treatment i.e., no biologic. The primary endpoint of the study, involving 170 patients randomized to placebo, Otezla 40mg BID or 30mg BID, was the proportion of subjects achieving clinical remission at week 12 as measured by Total Mayo Score.
The results showed 31.6% (n=18/57) of patients receiving 30mg Otezla twice daily achieved clinical remission compared with 13.8% (n=8/58) for placebo and 21.8% in the 40 mg arm (n=12/55). The safety profile was benign, similar to what was observed in previous psoriasis and psoriatic arthritis studies, and the Phase III program in UC is expected to commence this year.
Analysts have responded fairly positively to the data. Geoffrey Porges at Leerink issued a research note saying that "as usual Otezla won’t wow anyone with its efficacy, but it does have sufficient activity to justify further development and most likely succeed in a Phase III trial." He added, "We have been wrong before about Celgene’s 'less is more' strategy for its products, and Otezla can probably also carve out a meaningful niche in the relatively mild, or early disease settings in IBD."
Porges forecast peak sales of $500m for Otezla in UC, saying that one important question for Celgene will be how it advances the drug's development in this area. "The IBD indication is being flooded with new development candidates, and the most immediate issue is access to study sites, and patients, for pivotal trials," he added.
One of the new drugs in development is another Celgene offering, its closely watched ozanimod which is in late-stage development for UC and multiple sclerosis. Andy Hsieh, an analyst at William Blair, issued a note saying that having two assets targeting UC with non-overlapping mechanisms of action - Otezla is a phosphodiesterase 4 (PDE4) inhibitor and ozanimod is a sphingosine 1-phosphate (S1P) receptor modulator - "provides the company multiple shots on goal and opens the possibility for the potential combination of the two agents in order to maximize the therapeutic effect and duration."
Noting that while cross-trial comparisons are inherently difficult, not least in UC trials with variable length of the induction phase (6-12 weeks), Hsieh said that Otezla’s clinical profile "is comparable to other investigative therapies and approved agents." For the tumor necrosis factor inhibitor class, Johnson & Johnson's Remicade (infliximab) demonstrated the highest clinical remission rate of 28%-39%, compared with placebo of 6%-15% at week 8, while AbbVie Inc.'s Humira (adalimumab) and J&J's Simponi (golimumab) improved remission rate to 10-19% and 18%, respectively, from 9%, and 6% with placebo.
He also noted that Takeda Pharmaceutical Co. Ltd.'s Entyvio (vedolizumab), which is approved for patients who are intolerant, have inadequate response to, or relapsed to a TNF-targeting therapy, demonstrated a clinical remission rate of 17%, compared with 5% with placebo. As for ozanimod, the Phase II TOUCHSTONE study demonstrated a clinical remission rate of 16.4% for the higher 1.0 mg dose, compared with 6.2% for placebo.
Over at Deutsche Bank, the Otezla UC data were heralded as "a much-needed incremental win for Celgene particularly at a time when sentiment has been very negative and with the stock materially underperforming." The analysts wrote in an investor note that primary endpoint success in the 30 mg group "suggests a drug that is almost as good as Remicade, albeit much safer and more convenient," adding that Otezla in UC could achieve peak share of 15% which implies sales of $750m worldwide.
"We have always been intrigued by Otezla because we appreciate Celgene’s strategy of providing a safe, oral, low-cost option in pre-biologic setting in dermatology. If they can replicate that model in gastrointestinal the company should demonstrate success in that indication as well," they concluded.
Otezla made the headlines in the third quarter of 2017 with lower-than-expected sales after Celgene admitted its sales estimates for the drug had not adequately taken into account psoriasis and psoriatic arthritis market realities in the US. Analysts queued up to question the long-term prospects of the product but the fourth quarter saw a rebound with Otezla bringing in $371m, up 21.6% over the like, year-earlier period. (Also see "Celgene Admits It Screwed Up Otezla Estimates; Investors Lose Confidence" - Scrip, 26 Oct, 2017.) (Also see "Celgene Focuses On Deals, Pipeline As Post-Revlimid Future Draws Closer" - Scrip, 25 Jan, 2018.)
The drug is important to Celgene's inflammation and immunology franchise, especially given the discontinuation last October of GED-0301 (mongersen) in Crohn's disease, a drug acquired from Nogra Pharma Ltd. for $710m upfront in 2014. As Celgene plans for life after its multiple myeloma mega-blockbuster Revlimid (lenalidomide) goes off-patent starting 2023, the contribution of Otezla in all indications will be vital. (Also see "Celgene IBD Pipeline In Question As Mongersen Crohn’s Disease Trial Ends" - Scrip, 20 Oct, 2017.)