After the dust had settled on another J.P. Morgan Healthcare Conference in San Francisco, we caught up with Doug Ingram, the relatively new chief at rare disease biotech Sarepta, and discussed how he aims to remove the term “controversial” that we bio reporters keeping slapping in front of the company’s name.
Back in the fall of 2016, the biotech got off one of the unlikeliest approvals in modern FDA history when its Duchenne muscular dystrophy drug (DMD) Exondys 51 (eteplirsen) got the green stamp.
The drug works on around 13% of all DMD boys and targets the production of dystrophin, which is deficient in DMD and can lead to severely restricted movement in young boys affected, with many not living past young adulthood. The effect on dystrophin was however rather small; in fact, a few months before its approval, an FDA panel of outside experts voted narrowly, seven to six, that Sarepta did not provide substantial evidence from “adequate and well-controlled” studies that the drug produced dystrophin at a level that was reasonably likely to produce a clinical benefit.
On the big question, Do the clinical results of the single study provide “substantial evidence” of eteplirsen’s efficacy, seven of the panel members voted no, with three voting yes and three abstaining.
But, after much delay and hand-wringing at the FDA, the drug was approved five months later in an about-face. Its then-interim CEO Ed Kaye was visibly relieved, as were investors, as its stock jumped.
But the biotech has for around 18 months been labelled as controversial in most news stories given the fallout from the approval at the FDA, as well as from commentators, about whether this signaled the dumbing down of the regulator. In the end, the agency approved the drug based on a surrogate biomarker endpoint, the dystrophin increase in skeletal muscle observed in some Exondys 51-treated patients, but this was deemed pretty weak by some within the agency itself.
For its part, Sarepta believed in its drug and still does, but clearly does not want to rest on Exondys 51 as its one and only approval, or be forever the “controversial biotech.”
Ingram told FierceBiotech that the approval was an “unnecessary controversy,” but still left some “open questions about what it was going to be like in 2017.”
Ingram, a former Allergan exec who took over from Kaye last summer (after he bowed out to run a new startup), started his tenure in the summer with the aim to turn Sarepta from a one-hit wonder into a sustainable neuromuscular disease specialist, with many shots on goal.
How? During J.P. Morgan, he had a “singular focus,” and that was talking up the pipeline. The company has done a host of deals since Exondys 51 was approved in September 2016, including a pact last June with France’s Genethon and its preclinical microdystrophin gene therapy approach, which can target the majority of patients with DMD, as well as the deal announced during the last JPM conference, which has seen it work with the Nationwide Children’s Hospital, a pact that also focuses on the microdystrophin gene therapy program, as well as another form of gene therapy.
“We think Exondys 51 is fantastic,” Ingram said, “but it’s part of a journey. We have some very lofty aspirations: We want to treat as close as we can to 100% of children [with DMD] and extend and improve their lives.”
The way the company are trying to do this twofold: with RNA technology, and with gene therapy. The next-gen RNA tech is peptide-conjugated phosphorodiamidate morpholino oligomer, which now has six potential clinical candidates, which he said will cover around 43% of the DMD community (although all still very early stage). It also has a handful of gene therapy programs, as well as a CRISPR-Cas9 program, via its collaboration last October with Duke University.
“Two of those programs, we’re very excited about,” Ingram said. “We’ve already dosed children in both [of these trials] and will get preliminary results by the middle of this year.”
“This is R&D,” he said, “and you can never easily or fully predict or understand what’s going to happen, but we have a lot of different approaches, and there is a lot of great science going on at Sarepta, and one of these approaches is going to work.”
He also added, cautiously, that they may already have the answer to DMD in its gene therapy that has already dosed, but of course we won’t start to see the picture on that for a few more months. But Ingram is clear that the goal is for the next-generation therapies to be curative: “I didn’t come to Sarepta to take a job; I looked at its pipeline and thought, if we can achieve brilliantly as an organization, then we have the opportunity to profoundly change the lives of these kids.”
Ingram said the guidance for this year is for around $300 million: “And we’re going to take that, plus more besides, and funnel that directly into our R&D efforts, and we’ll have as many as 16 therapies in development this year.”
When I interviewed Kaye in the week after Exondys 51 was approved, he said he hadn’t spent years of his life at the biotech, and getting off that approval, just to sell the company on. Despite having an M&A background, Ingram has the same philosophy and laughed when I asked whether he would want to become a unit of Pfizer, Merck or some other Big Pharma.
“We all here strongly believe that we can become one of the biggest genetic medicines companies in the world over the next five years, if we execute flawlessly. That’s the goal, to build the company up.”
And what does he think of FDA Commissioner Scott Gottlieb, M.D.? “I think Gottlieb is fantastic, someone who really understands, in a forward-thinking way, what we should be focusing on between safety and rapidly bringing innovative new therapies to market. Everything we hear from the commissioner sounds like a positive for the industry.”
But getting a drug approved is only half the battle these days, with the politics of pricing also becoming an increasing part of the equation for biotech CEOs. Exondys 51, which is only licensed for a very small population given its target (and a subpopulation of that as well), is priced at around $300,000 per child, although it is based on weight and so can cost much more.
Drug pricing is a natural topic, Ingram said. “There is only a finite amount of money for healthcare, so we need to think about value. But we need to thread the needle on this in an appropriate way; we all need to be smart about this [the drug pricing debate]. Just bluntly cutting costs could be dangerous, because we risk cutting innovation and reinvestment into R&D.
“But there is clearly waste in the healthcare system regarding procedures and older therapies; when we think about cost containment, we instantly think about newer therapies, but the newest therapy is usually the least burdensome on the system and the most innovative.”
Is the pricing debate affecting how he approaches his pipeline now? “If we can do great things, then I’m confident that the healthcare system is going to reward that, especially for us, when it could benefit these children with such a damning disease.”
Sarepta, with a market cap edging to $4 billion, was up 4% this morning.