Ionis Pharmaceuticals has dropped more data on its AstraZeneca-partnered treatment for hereditary transthyretin-mediated amyloid polyneuropathy (ATTRv-PN), shedding a little more light on how the antisense candidate matches up to Alnylam’s incumbents.
In June, AstraZeneca and Ionis revealed their clinical trial of eplontersen met its co-primary endpoints at a 35-week interim analysis, leading the partners to aim to file for FDA approval this year. However, the top-line data release was light on details. In the absence of hard numbers, it was impossible to gauge how the drug candidate compares to Alnylam’s Amvuttra and Onpattro.
Teresa Coelho, M.D., an investigator on the trial, presented some data at the International Symposium on Amyloidosis on Wednesday, but multiple questions that will shape the competitiveness of the drug remain unanswered, at least publicly.
Here’s what we know: Eplontersen achieved an 81.2% mean drop in serum transthyretin concentration compared to baseline, indicating a reduction in the TTR protein that drives ATTR and causing the trial to hit one of its co-primary endpoints.
On the second co-primary endpoint, eplontersen had a significant effect on the mNIS+7 measure of neuropathic disease progression, resulting in a hit with a p-value of less than 0.0001. AstraZeneca and Ionis also linked the candidate to a significant improvement on the Norfolk QoL-DN patient-reported quality of life questionnaire. The trial hit that secondary endpoint with a p-value of less than 0.0001.
The change in serum TTR level puts eplontersen roughly on a par with Alnylam’s Amvuttra and Onpattro. Alnylam linked (PDF) Onpattro to an 84% reduction in serum TTR at 18 months and Amvuttra to an 83% drop at nine months, around 39 weeks. With an 81% drop at 35 weeks, eplontersen is in the same ballpark as its rivals. The unanswered question is how the TTR decline translates into clinical outcomes.
Ionis’ statement lacks further details of the numbers behind the hits on the mNIS+7 and Norfolk QoL-DN endpoints. We know that Alnylam’s Amvuttra achieved placebo-adjusted changes of 17.0 and 16.2, respectively, on mNIS+7 and Norfolk QoL-DN after nine months. Ionis’ statement is devoid of comparable details for eplontersen.