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Early Data for Celgene’s Oral Crohn’s Drug Gets Mixed Reaction

Xconomy New York — 

Celgene late Sunday provided more details on one of the more important drugs in its pipeline, a pill the Summit, NJ, company is developing for inflammatory bowel disease. Analysts on Wall Street are mixed on the clinical results.

The data, which Celgene is presenting at United European Gastroenterology Week in Vienna, Austria, are an early look at an ongoing, 63-patient Phase 1b study of GED-0301 (mongersen). The results represent the first time patients with Crohn’s (a form of IBD) on mongersen were given endoscopies to show how the drug is impacting the size of their ulcers. Previously, mongersen’s effects were measured only by the reduction of signs and symptoms of the disease.

In the study, Celgene enrolled 63 patients with moderate-to-severe Crohn’s. Some had previously been treated with at least one biologic drug—like infliximab (Remicade) or adalimumab (Humira), and others hadn’t. These patients were randomized, split into three groups, and given mongersen either once a day for 12 weeks; once a day for 8 weeks followed by four weeks on a placebo; or once a day for 4 weeks followed by 8 weeks on a placebo.

Celgene (NASDAQ: CELG) is reporting interim results after these 12 weeks of treatment. The company will follow patients for another 52 weeks off treatment to see the results, and afterwards eligible patients will be able to go back on mongersen for another 100 weeks as part of an extension study. These results, along with the larger Phase 3 trial Celgene is running, will provide the definitive answers on mongersen. But today’s endoscopy results are an early snapshot of the drug’s potential.

Last month, Celgene said that patients on the drug in the Phase 1b trial showed an endoscopic response—defined as a 25 percent improvement from the start of the study—after 12 weeks of treatment. Without giving specific numbers, Celgene said in September that “a proportion of patients” in all of the different treatment groups (as Celgene tested three different regimens of mongersen) improved, that there were remissions in each group, and that no new safety problems popped up.

On Sunday, Celgene provided more details, but still left some questions unanswered. Celgene said of the 52 patients whose endoscopies could be evaluated, 37 percent met the 25 percent endoscopic improvement threshold, with no meaningful differences across the three tested groups. The company didn’t specify how the drug performed in each of these groups, however, or what the total remission rates were. Celgene only said that 48 percent of patients on the drug for 12 weeks were in remission. More data will be presented in Vienna this week.

Celgene measured the drug’s effects both via scores on the Crohn’s Disease Activity index (CDAI, a survey used to quantify patients’ Crohn’s symptoms) and the Simple endoscopic score for Crohn’s disease, or SES-CD, in which investigators use endoscopy images to gauge patients’ disease. Patients in the trial started with CDAI scores of between 220 and 450, and those on mongersen for 12 weeks saw those scores drop by an average of 133 points. Of those patients, 67 percent saw their CDAI scores improve by at least 100.

Celgene said the rates of side effects were “low and similar across treatment groups” and that, again, no new safety problems popped up.

Biotech analysts weighing in on the data offered mixed opinions. Some deemed the figures impressive, while others felt the information so far is inconclusive. In a research note, Jefferies analyst Brian Abrahams wrote that given the small size of the trial, the design of the study, and “mixed” endoscopy data—there wasn’t a dose-dependent improvement on patients’ endoscopies—the results are difficult to interpret. Leerink Partners’ Geoffrey Porges wrote that the data suggest mongersen may be a viable drug and its benign safety profile so far bodes well, but it’s “hardly [a] transformative” drug given the modest effectiveness shown so far.

Mongersen also has competition from a rival pill being developed by Gilead Sciences (NASDAQ: GILD) and Galapagos also in clinical testing.

RBC Capital Markets’ Michael Yee was more bullish on the data, calling the results promising, “better than expected,” and helping bolster the idea that mongersen could be a $1 billion to $2 billion in sales per year drug for Celgene over time. Yee expects the drug’s effects on Crohn’s will get better over time. It “could be the [apremilast (Otezla)] of Crohn’s disease,” he wrote, referencing Celgene’s arthritis pill, which won FDA approval in 2014 and climbed to $472 million in sales last year. “Even if [it’s] not the most potent drug, it can still be a $1 billion-plus drug for [Celgene] if well tolerated, good safety, convenient, and good efficacy as the world moves to more orals,” he wrote.

As with apremilast, Celgene’s plan with mongersen is that a pill could be a significant differentiator in a market dominated by injectable biologic drugs. Patients with Crohn’s and ulcerative colitis (another form of IBD) typically end up on injectable biologics such as infliximab or adalimumab, which generate billions of dollars in sales every year. Many patients don’t respond to these biologics, however, and in some cases their effects diminish. Apremilast and mongersen are part of Celgene’s plan to branch out from its flagship blood cancer drugs and amass a second franchise in inflammatory diseases.

Celgene acquired mongersen when it paid Ireland’s Nogra Pharma $710 million up front in a 2014 licensing deal. Mongersen is meant to reduce the levels of a protein called Smad7, high levels of which are implicated in gut inflammation in people with IBD.