Alnylam Pharmaceuticals’ investigative patisiran treatment improves overall health and prevents worsening of walking ability in patients with familial amyloid polyneuropathy (FAP), according to a new analysis from the APOLLO Phase 3 study.
FAP, also known as hereditary ATTR (hATTR) amyloidosis, is caused by mutations of the transthyretin (TTR) gene that lead to the production of faulty TTR proteins. Patisiran works by preventing the production of these disease-causing faulty proteins, according to Alnylam.
The randomized, placebo-controlled, multi-center APOLLO Phase 3 study (NCT01960348) evaluated the safety and effectiveness of patisiran in adults with FAP. It involved 225 FAP patients from 19 countries who were randomized to receive either patisiran (148 patients) or placebo (77 patients) intravenously once every three weeks for 18 months.
An additional analysis of the APOLLO results were disclosed in six presentations at the Peripheral Nerve Society (PNS) Annual Meeting, July 22-25 in Baltimore, Maryland.
Overall health was additionally measured through the EuroQOL-5-dimension 5-level (EQ-5D-5L), which comprises five domains of health status — mobility, self-care, usual activities, pain/discomfort, and anxiety/depression — and the EuroQOL visual analogue scale (EQ-VAS) — which records the patient’s self-rated health.
After 18 months, a greater proportion of individuals from the patisiran group (between 70-81% percent) showed similar or improved scores in each EQ-5D-5L domain, compared to that of patients receiving placebo (between 21-45%).
While patients receiving patisiran showed improvements in the EQ-VAS scores, those receiving placebo had a strong score decline, and these differences were statistically significant.
“Patisiran treatment, relative to placebo, may help patients maintain or improve mobility and independence, reduce anxiety and depression, and favorably impact overall health status,” Eric Green, vice president and general manager of the TTR Program at Alnylam, said in a press release.
Additional analyses showed that patients with a greater improvement in the modified Neuropathy Impairment Score + 7 (mNIS+7) — which assesses nerve damage-related symptoms and was the study’s primary goal — after 18 months of treatment had consistent and significantly higher chances of having a stabilized or improved walking ability.
Improvements in FAP Stage and polyneuropathy disability (PND) score — both used to assess disease severity and largely based on walking ability — were only seen in the patisiran group of patients, and worsening occurred twice as frequently in the placebo group compared to the patisiran group, which was statistically significant.
This suggested patisiran has the potential to prevent the FAP-related worsening of walking function in these patients.
Also, a new analysis of the infusion-related reactions observed in patients receiving patisiran showed that their frequency decreased over time, and that only one patient (less than 1 percent of patients) discontinued treatment due to an infusion-related adverse event.
Indirect comparison between APOLLO results and clinical results of Vyndaqel (tafamidis) — an approved therapy for FAP in the European Union and in several countries in Latin America and Asia — showed that patisiran was significantly associated with greater improvements in FAP-related symptoms and quality of life.
The new analysis also pointed out that patients receiving placebo had significant disease progression as early as nine months, regardless of their disease severity at the start of the study.
Green noted that this finding highlights the need for an early effective treatment in FAP patients to prevent further disease worsening and associated degeneration.
“We believe the new data presented underscore the potential clinical benefit of patisiran for patients with hATTR amyloidosis [FAP],” Green said.
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