A race is on to bring two new RNA-based drugs for a rare, debilitating nerve disease called familial amyloid polyneuropathy (FAP). And GlaxoSmithKline has just dropped out of it.
This morning, Ionis Pharmaceuticals (NASDAQ: IONS) said that it has regained full rights, from GSK, to a drug called inotersen, which the Carlsbad, CA, company expects to submit to regulators in the U.S. and Europe for a review this year. If the FDA approves inotersen, it could become the first marketed treatment in the U.S. for FAP.
Ionis partner GSK dumped the drug—as well as another experimental medicine Ionis plans to develop for an eye disease, and possibly other conditions—as part of an R&D shakeup engineered by new CEO Emma Walmsley. The British pharma is weighing the future options for its rare disease business, including a sale, and that uncertainty put the Ionis drugs on GSK’s chopping block.
Shares of Ionis fell 6.7 percent in pre-market trading on Friday.
GSK’s decision comes at a crucial time for Ionis. It is preparing to file for approval of inotersen, and trying to stay a step ahead of rival Alnylam Pharmaceuticals (NASDAQ: ALNY). The two could be locked in a commercial battle in the near future.
Inotersen and Alnylam’s patisiran are two RNA-based drugs being developed for FAP. The disease, a form of transthyretin amyloidosis causes amyloid proteins to build up in tissues of the body and, ultimately, damage to the nerves, heart, and other organs. About 10,000 people have the nerve-damaging form of TTR amyloidosis, FAP, and they tend to live another 5 to 15 years after symptoms crop up.
The only treatment options for FAP patients are a liver transplant, or Pfizer’s tafamidis (Vyndaqel), which is approved in Europe but not in the U.S. Ionis could be the first to change that, having succeeded in a Phase 3 trial in May, while data from Alnylam are expected in September. But even though Ionis has a head start, expectations for inotersen were tempered when worrisome side effects—dangerously low platelet counts and kidney problems—occurred in some patients in clinical testing.
On a conference call in May, Ionis executives downplayed those issues. Ionis senior vice president of drug discovery Brett Monia said the safety concerns can be monitored, are “manageable,” and that “early signals [of safety problems] are reversible.” Ionis also said it has since changed how it tests for low platelet counts and kidney problems and that all of the serious side effects occurred before these measures were implemented. A long-term safety study is underway, and Ionis is presenting full data from its Phase 3 study at a medical meeting in October. Both will go a long way to showing exactly how the benefits of taking inotersen compare to the safety risks.
In the meantime, Leerink analyst Paul Matteis wrote in a note that GSK’s decision to pass on its option to inotersen wasn’t a huge surprise given the pharma’s shifting strategy, but nonetheless creates new hurdles. The decision “may increase investor scrutiny” on inotersen’s already closely watched safety profile, he wrote, and Ionis might now be “behind the curve with respect to launch preparedness” without GSK’s help. Ionis, for its part, said in a statement it is in discussions with new partners to replace GSK and may form a subsidiary to help sell inotersen in North America. (Ionis already a similar type subsidiary in Akcea Therapeutics, which owns an Ionis RNA heart drug close to market.)
The coming Phase 3 data for Alnylam, meanwhile, are a huge event for the company and the RNA drug field overall. Should Alnylam succeed, it will have the chance to bring not only its first drug to market, but the first ever medicine using RNA interference—a way of silencing a gene so it doesn’t produce a disease-causing protein. Success would also keep Alnylam in lock-step with Ionis. Here’s more on Ionis, Alnylam, RNA drugs, and the race between the two to bring a new FAP treatment to market.