- Ionis Pharmaceuticals, Inc. is preparing for launch of its antisense drug, inotersen, for the treatment of hereditary ATTR (hATTR) amyloidosis with polyneuropathy and is well on the way towards a commercial partnership, according to the company at its third quarter 2017 earnings presentation this week.
- Inotersen, which will face competition from Alnylam Pharmaceuticals, Inc.'s patisiran, has just been submitted for approval in the U.S. and Europe, with accelerated assessment in the EU and fast track status in the U.S.
- Ionis plans to begin an expanded access program in the U.S. by the end of this year, and is in discussions with potential marketing partners.
Last week Alnylam and partner Sanofi SA announced results from the APOLLO Phase 3 study of RNA interference therapeutic patisiran for the treatment of hereditary ATTR (hATTR) amyloidosis with polyneuropathy. Patisiran met all of its primary and secondary endpoints with statistical and clinical significance, improving neuropathy scores and symptoms, as well as showing cardiac and quality of life benefits.
Meanwhile, results from the Phase 3 NEURO-TTR of inotersen showed significant benefits in quality of life and in measures of neurological disease compared with placebo; half of inotersen-treated patients improved their quality of life from baseline. Inotersen is dosed as a weekly subcutaneous treatment, and is potentially self-administered; patisiran is dosed intravenously.
While comparisons are difficult, as the studies aren't completely comparable, these results suggest that patisiran is disease-modifying, whereas inotersen is simply disease-stabilizing.
However, Ionis Pharmaceuticals, Inc. used its third quarter earnings call to show its confidence in inotersen and suggest it could compete with the Alnylam drug despite recent study results.
"I think both drugs are likely to be used. For example, the quality of life data for inotersen is virtually indistinguishable to that of patisiran. We believe that the benefit seen with inotersen treatment in the NEURO-TTR study, combined with its superior convenience, could make inotersen the treatment of choice for this patient population," said Sarah Boyce, chief business officer at Ionis Pharmaceuticals, on a Tuesday call with analysts. "We are optimistic that inotersen will command a significant share of the market. We could change how the disease is diagnosed and treated."
Boyce added that the company is pleased with the cardiac data so far and aims to get it into the label in the future.
Last week, Ionis submitted a marketing authorization application to the European Medicines Agency for inotersen, based on the phase 3 NEURO-TTR study in patients with hereditary TTR amyloidosis (hATTR). This will be reviewed under the EMA's accelerated assessment program, and met the last deadline for accelerated assessment in the EU for 2017.
Following this, on Monday, Ionis submitted a New Drug Application to the Food and Drug Administration. Inotersen has orphan drug designation and fast track status in the U.S. Alnylam plans to submit patisiran in the U.S. by the end of 2017, and in Europe in early 2018. Ionis believes that inotersen's earlier filings could give the company a competitive edge and a first-to-market advantage.
"Inotersen has the potential to contribute significantly to our commercial revenue beginning next year," said Stanley T. Crooke, chairman of the board and CEO. "Our commercial team is preparing for launch. Over the last few months, knowing that we have competition, we have looked at what we expected of inotersen in the market. We have talked to patients, investigators and physicians, and we are confident that we can take a significant portion of the market."
When quizzed about pricing, Crooke was reluctant to answer, only suggesting that Alnylam has signaled Soliris type prices. Alexion Pharmaceuticals' Soliris (eculizumab) currently carries a pricetag in the U.S. of more than $400,000 and was once considered the most expensive drug in the world. Crooke's comment indicates Ionis thinks it can out maneuver Alnylam on price as well as dosing.
GlaxoSmithKline plc dropped its option to inotersen in August 2017 as part of an R&D overhaul, and Ionis is looking into the possibilities of a new partnership.
"We could commercialize inotersen entirely ourselves, we could find a partner that adds value and market strength. Or we could have a combination of the two," said Crooke on the call. "We are pleased with the level of interest that we have seen from partners, and are well along in discussions. We are looking for a company that is ready to contribute straight away, with the infrastructure and sales force already in place. However, we are also well along the way to be able to launch the product ourselves."
Inotersen isn't Ionis' only weapon of choice in the battle for the ATTR market. The company is developing a ligand conjugated antisense follow-on therapeutic, based on inotersen. This is in preclinical development, with clinical trials planned before the end of 2018. According to Crooke, it has potential to be a more potent and a convenient approach to treatment.
"We are moving this forward rapidly and with high priority," said Brett P. Monia, SVP of antisense drug discovery at Ionis. "We learned a lot through the NEURO-TTR study."
"We are putting together a streamlined clinical program for all patients with TTR," added Crooke.