Alnylam has emerged victorious from its hereditary TTR amyloidosis (hATTR) data face-off against Ionis. Data presented by the RNAi pioneer suggest its patisiran has the edge over Ionis’ inotersen in terms of safety and efficacy, although it remains to be seen whether this translates into market share.
Both companies were in Paris this week to present data from their phase 3 trials. The event gave doctors and investors a chance to look at the full data from both studies and assess which is likely to be the best option for patients. The stock activity of the companies tells the story of which biotech was deemed the winner on the day.
Shares in Alnylam rose 10%. Shares in Ionis fell 10%.
The diverging fortunes of the two stocks is underpinned by comparisons of the safety and efficacy data, which were stark enough for investors to overlook the general risks of cross-trial comparisons and specific differences in the duration of the studies and send the stocks in opposite directions.
Both trials met their primary endpoints of performance against the neuropathy impairment score mNIS+7. But patisiran posted a 34-point difference against placebo, compared to a 20-point improvement for inotersen.
Notably, Alnylam’s trial linked patisiran to a six-point improvement from baseline, suggesting the condition of patients on the drug got better. Inotersen, in contrast, appears to stabilize the disease. The mNIS+7 scores for patients on Ionis’ antisense drug declined by five points.
Patisiran also outperformed inotersen against a diabetic neuropathy quality-of-life scale. Inotersen posted a mean 12-point benefit over placebo after 15 months. Patisiran chalked up a 21-point gain after 18 months.
Both drugs delivered data suggesting they benefit cardiac disease, a comorbidity seen in more than half of the participants in each study.
The unfavorable comparisons for inotersen continued into the safety data, an area that has dogged Ionis throughout development. Five patients died in the inotersen arm, compared to none on the placebo cohort. Ionis thinks four of the deaths were due to disease progression. But the disparity in the death rates further complicates the situation for a drug that was rocked by safety scares in development.
Assuming Ionis can convince regulators the benefits of inotersen outweigh the risks, it will have a shot at outcompeting patisiran in ways not evident in the 15 and 18-month data. The speed at which mNIS+7 achieved statistical significance is one way Ionis can try to differentiate inotersen.
Another is the dosing. Inotersen is delivered subcutaneously. Patisiran requires an infusion, which takes upward of one hour and in the near term will be performed at clinics.
These factors will come into play as healthcare systems, particularly in Europe, weigh up which, if either, of the hATTR drugs represents good value. The key, and still unknown, data point in those evaluations is price.