Allergan's Open Science Business Model Leads To Successful IBS Study

By Ed Miseta, Chief Editor, Clinical Leader

In January 2016, The New England Journal of Medicine published the results of a pivotal Phase 3 study of VIBERZI (eluxadoline), a treatment for adults suffering from irritable bowel syndrome (IBS) with diarrhea. The results were from two randomized, multicenter and multinational double-blind, placebo-controlled trials. In the trials, most patients treated with VIBERZI had simultaneous improvement of both diarrhea and abdominal pain. David Nicholson EVP of Brands R&D for Allergan, spoke with me about the trials and what they mean to patients dealing with the symptoms of the disease.

Ed Miseta: Allergan has a business model that you refer to as open science. Can you explain what that means?

David Nicholson: Sure. What we mean by that is we try to fill our pipeline by interacting with the external world. That includes both large and small companies in the biotech world that have molecules that might apply to any of our therapeutic areas of interest. It is our belief that there is much more R&D activity taking place in the external world than any one company could possibly perform in-house. We like to view the external world department that performs early development research. Therefore, we are continuously looking at the outside world to pull projects into Allergan for finalization of development and commercialization.

Miseta: Allergan recently posted positive results from a clinical trial involving the use VIBERZI to treat IBS-D. Can you discuss how that medicine made its way into the Allergan pipeline?

Nicholson: We have a significant interest in GI (gastro-intestinal) disorders in general, and IBS in particular. As a result, we are always on the lookout for opportunities in those areas. A few years ago, we identified Furiex Pharmaceuticals as an interesting company with an asset called eluxadoline. It is a mixed opioid receptor antagonist, which they had in development for IBS with diarrhea. The Phase 3 trials were actually performed by Furiex, and we acquired the asset once they completed those studies. We then worked together with some of their employees who joined our company to complete the regulatory filings and obtain approval for eluxadoline (VIBERZI) in the U.S.

Miseta: What will these positive results mean to patients suffering from IBS?

Nicholson: IBS is very much a multi-factorial disorder which is associated with abdominal pain, discomfort, and altered bowel function. People who have IBS with diarrhea have a sudden and urgent need to have a bowel movement that results in a loose and watery stool. Patients can also alternate between periods of constipation and diarrhea, making it a very unpleasant disorder.

We currently have another GI product on the market called Linzess, which we co-market in the U.S. with Ironwood Pharmaceuticals, and that is an agent for IBS with constipation. So we feel it is very useful for physicians treating patients with IBS to have one company that is able to offer a medicine to treat both of these conditions.   

Estimates vary as to how many patients in the U.S. suffer from IBS with diarrhea, but it is believed to be around 10 to 15 million adults. Because it is often believed to be undiagnosed, its prevalence may be greater. At the moment there are limited therapeutic options. Diets and fiber are often used for treatment, along with some antibiotics and over-the-counter options as well. But in our opinion there is a growing need for new options, which is why we believe VIBERZI will be a very useful agent for the treating physicians.

Miseta: Were there any challenges faced by Furiex in getting this Phase 3 trial off the ground?

Nicholson: I believe the challenges were similar to those inherent in any clinical program. One was certainly patient recruitment. For this study Furiex did a great job of working with a CRO to rapidly recruit for the trial. I believe we ended up with a fairly diverse set of patients with an average age of 45 years with two-thirds of participants being female, 11 percent black, 27 percent Hispanic, and 86 percent white. Other than recruitment there were not too many hurdles that needed to be overcome. This particular compound is restricted to the GI tract, and it has very low systemic bioavailability, which helps to reduce the side effect profile. Pancreatitis can be associated with the active agent and can be exacerbated by patients who abuse alcohol. That was something we had to address with the treating physicians when beginning the two Phase 3 studies.

Miseta: What were the differences between the two studies?

Nicholson: We had two 12-week efficacy portions of the clinical studies, and we looked at two different doses, 75 mg and 100 mg. We wanted to make certain we administered the right dose in Phase 3. It is not always common to look at two different doses in Phase 3, but in this case it was viewed as a wise thing to do. We looked at a composite endpoint of an improvement in pain and in diarrhea symptoms. A patient had to meet both criteria to be considered a responder.  That was a high hurdle for us to set for ourselves, but we only wanted to move forward with the agent if we were convinced of the efficacy on both counts.

Miseta: Were there any other key takeaways from these studies?

Nicholson: One of the things that really stood out to me was the amount of unsolicited testimonials we received regarding the efficacy of the medicine. For some patients, there was a dramatic improvement in their symptoms, and eluxadoline provided them with relief that they were not able to attain from other agents currently on the market. That tells us something about the efficacy of the agent, but also points to the significant unmet need for patients suffering from the condition. It is massively disruptive to the daily lives of patients and clearly the agents that had been on the market were not sufficiently treating the condition and the symptoms. For those reasons we believe eluxadoline will be of great benefit to patients. And obviously the goal of the industry will be to continue to develop new and better agents to treat these patients. Each effective product that comes along will simply raise the bar for any future agents that are under development.