Onpattro (patisiran) is more effective than Tegsedi (inotersen) at reducing neurological impairment and improving quality of life in people with familial amyloid polyneuropathy (FAP), a comparison of data from two clinical trials reported.
The study, “Indirect treatment comparison of the efficacy of patisiran and inotersen for hereditary transthyretin-mediated amyloidosis with polyneuropathy,” was published in the journal Expert Opinion on Pharmacotherapy.
FAP is a hereditary condition caused by mutations in the TTR gene, which contains instructions for the TTR protein. These mutations result in the buildup of an abnormal form of TTR protein, especially in the nervous system, heart, kidneys, and eyes.
Onpattro, by Alnylam Pharmaceuticals, and Tegsedi, developed by Ionis Pharmaceuticals, are both approved to treat the disorder. Both block the production of TTR protein, thereby reducing toxic buildup.
However, no studies have directly compared the effectiveness of these therapies.
Scientists at Alnylam and collaborators at the Mount Sinai Medical Center in New York and the Analysis Group in Boston conducted an indirect comparison, using data extracted from two separate clinical trials that evaluated these medicines against a placebo prior to their approval. (Three of this study’s six researchers were Alnylam employees at the time this work was conducted.)
“In this study, we add to the literature by indirectly comparing the relative efficacy of [Onpattro] and [Tegsedi] for [FAP],” the scientists wrote.
“The APOLLO and NEURO-TTR studies had comparable inclusion and exclusion criteria, neuropathy endpoints, and were largely similar in terms of trial design and methodology,” the researchers wrote. “However, a few differences existed,” including different versions of neuropathy scales, follow-up durations, and certain baseline (study start) characteristics.
Common outcomes that were compared included the modified Neuropathy Impairment Score+7 (mNIS+7) to characterize and measure neurological impairment (neuropathy), and Norfolk QOL-DN to gauge the impact on life quality.
Due to differences in the mNIS+7 versions used in each trial, the mNIS+7 endpoint defined in the NEURO-TTR study (mNIS+7Ionis) was applied here. As the NEURO-TTR study was a 15-month trial while APOLLO lasted 18 months, changes on mNIS+7Ionis and Norfolk QOL-DN scores at 15 months were estimated for patients in the APOLLO study.
Differences in demographic and disease characteristics were also noted between the NEURO-TTR and APOLLO study populations, so a method that adjusts for imbalances in baseline characteristics was used. After adjustment, the number of patients who received Onpattro in the final comparison was 90 and 47 for placebo.
Analysis revealed the mean 15-month changes from before treatment in mNIS+7Ionis favored Onpattro compared to Tegsedi, with a 16.2 point decrease in score (higher scores mean more impairment).
The proportion of patients who experienced mNIS+7Ionis improvement or no change was significantly higher for Onpattro than for Tegsedi, and the odds of improvement were significantly higher for patients treated with Onpattro.
Similarly, mean changes from baseline on Norfolk QOL-DN favored Onpattro compared to Tegsedi, with a reduction of 11.6 points (indicating improvement). The proportion of patients who reported a better quality of life relative to baseline was higher for Onpattro than for Tegsedi, and the odds of improvement were significantly higher for patients treated with Onpattro.
Body-mass-index (BMI), a measure of body fat, and PND score, a method used to classify FAP progression, were also compared between trials. The mean differences in BMI at 15 months were more favorable for Onpattro compared with Tegsedi, and the proportion of patients who improved or showed no change in PND scores was also significantly higher among those given Onpattro at 18 months compared to Tegsedi at 15 months.
“Overall, the totality of evidence across the variety of indirect comparisons conducted suggests that [Onpattro] has greater treatment effect than [Tegsedi] for neuropathy and quality of life outcomes in patients with [FAP],” the researchers concluded.
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