- Ionis Pharmaceuticals and partner AstraZeneca have strengthened their case for approval of a rare disease drug now under regulatory review in the U.S., revealing Monday detailed data from a late-stage clinical trial of the therapy.
- Results from the study showed the therapy, called eplontersen, halted progression of patients’ disease, a progressive genetic condition known as transthyretin amyloidosis with polyneuropathy. Study participants treated with the drug also reported improved quality of life, according to the companies.
- Ionis and AstraZeneca have already submitted eplontersen for approval by the Food and Drug Administration, which has set a deadline of Dec. 22 for its decision. The companies’ application was based on earlier, interim data from the same trial.
Eplontersen is a successor to Tegsedi, another Ionis-developed drug previously approved to treat nerve damage caused by transthyretin amyloidosis. Both are "antisense" medicines that use interfering strands of RNA to gum up production of transthyretin protein, and thereby treat the root of the disease.
Tegsedi hasn’t sold as well as a competing medicine for the condition developed by Alnylam Pharmaceuticals, which last year won FDA approval of a second, more convenient version.
Eplontersen is meant to be a more potent rival, designed using an Ionis technology called LICA that allows it to be given once monthly rather than every week like Tegsedi.
The study results detailed Monday show eplontersen to be at least as effective as Tegsedi in treating polyneuropathy associated with transthyretin amyloidosis, although the drugs have not been compared head to head.
In the trial, data from patients treated with eplontersen were compared against outcomes from the control group in a 2017 trial of Tegsedi. Treatment led to an average 82% reduction of TTR protein in the blood, compared to an 11% decrease among that external control arm.
More importantly, eplontersen treatment appeared to halt disease progression on a quantitative assessment of muscle weakness and sensory loss known as mNIS+7. Study participants treated with the drug experienced a less than one-point average increase on the sale, while those in the external placebo group had an increase of 25 points.
“In the past, patients with hereditary transthyretin amyloid polyneuropathy usually deteriorated given the limited available treatments,” said Sami Khella, a professor of clinical neurology at the University of Pennsylvania and a trial investigator, in a statement provided by Ionis and AstraZeneca.
Overall, nearly half of eplontersen-treated patients showed an improvement in neuropathy, versus 17% in the external group of patients given placebo.
Treatment was also associated with improved quality of life and met other secondary study goals. According to the companies, rates of adverse events that occurred alongside treatment were similar to what was previously reported for the external placebo group “across all major categories.”
Ionis and AstraZeneca split rights to eplontersen in the U.S., while AstraZeneca is responsible for development and commercialization in the rest of the world, excepting Latin America. Ionis recently sold off some of its royalty rights to other drugs to fund the planned launch of eplontersen and two other experimental medicines nearing market.
In addition to studying the drug as a treatment for polyneuropathy tied to transthyretin amyloidosis, the companies are also testing it as a treatment for cardiomyopathy — a more common and deadlier form of the condition.
Alnylam last year reported positive results for its drug Onpattro in cardiomyopathy, and is studying its second-generation version Amvuttra for that variant of the disease as well.