August 11, 2017
By Mark Terry, BioSpace.com Breaking News Staff
The other shoe—or shoes—are dropping after the announcement in late July that GlaxoSmithKline was making major changes and killing more than 30 preclinical and clinical programs. Today, Carlsbad, Calif.-based Ionis Pharmaceuticals announced that GSK had declined its options on both inotersen and IONIS-FB-Lrx, which gives Ionis back control of those rights.
Inotersen is designed for patients with TTR amyloidosis (ATTR), and Ionis is wasting no time pushing forward with the drug. B. Lynne Parshall, Ionis’ chief operating officer, said in a statement, “We are pleased to move forward these two important drugs ourselves. We are prepared to independently advance inotersen and remain on track to file for marketing approval of inotersen in the U.S. and EU this year.”
The company had recently completed the Phase III NEURO-TTR trial of inotersen, where it met both primary clinical endpoints of neurological disease progression and quality of life in patients with hATTR-PN.
IONIS-FB-Lrx is in development to treat complement-mediated diseases. Earlier this year, Ionis completed a Phase I trial where the drug showed dose-dependent reductions in plasma factor B (FB) and showed safety and tolerability that supported more clinical development. The company plans to start the first Phase II trial of the drug in patients with dry age-related macular degeneration (AMD) later this years, and possibly in other indications in 2018.
“IONIS-FB-Lrx represents a unique opportunity to develop a treatment for underserved rare and broad patient populations affected by a variety of complement-mediated diseases,” said Brett Monia, Ionis’ senior vice president of drug discovery and franchise leader for oncology and rare diseases, in a statement. “IONIS-FB-Lrx takes advantage of our LICA technology, which can potentially provide greater patient convenience by allowing for significantly lower doses and less frequent administration.”
In many ways, this sounds like good news for Ionis, although it comes with its own set of obstacles. Inotersen is in a bit of a race with Alnylam Pharmaceuticals ’ lead drug patisiran. Inotersen has also had some safety concerns, despite its success in Phase III.
“Our goals for inotersen are to maximize its commercial success and optimize our commercial participation,” said Sara Boyce, Ionis’ chief business officer, in a statement. “To achieve these goals, we are actively considering forming a commercial subsidiary to commercialize or co-commercialize inotersen in North America, as well as other options. Our recent experience building a commercial subsidiary has prepared us for this opportunity. We have substantial interest from potential partners and are in discussions with several parties. We believe that, together with the right commercial partner, we can maximize the commercial success of the drug worldwide.”
Paul Matteis, an analyst with Leerink wrote in a note to investors, “Normally in such a situation like this investors might worry that there’s some not-yet-seen element of the full data that may be problematic or disconcerting. To this point—given the well documented safety issues associated with Inotersen (i.e., thrombocytopenia), GSK’s decision may increase investor scrutiny on TTRrx’s safey profile as it is depicted in additional full data presentations this fall (American Neurological Association, Oct. 15-17, others).”
GSK will continue with two other Ionis compounds, IONIS-HBVRx and IONIS-HBV-LRx, which are currently in Phase II studies. Ionis’ chief executive officer, Stanley Crooke, said in a statement, that the company is now “accelerating the expansion of our TTR program for patients with cardiomyopathy due to TTR amyloidosis and the development of our LICA follow-on drug. Our experience in the completed Phase III NEURO-TTR study provides important information to aid in design of a study in patients with cardiomyopathy due to TTR amyloidosis. We have already identified a more potent and convenient LICA follow-on and we expect development of the LICA drug to also proceed rapidly.”
