Eplontersen improves neuropathy and QoL in hereditary transthyretin amyloidosis with polyneuropathy: JAMA.

Written By :  Aditi
Medically Reviewed By :  Dr. Kamal Kant Kohli
Published On 2023-10-02 13:15 GMT   |   Update On 2023-10-02 13:24 GMT
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For managing hereditary transthyretin (ATTRv) amyloidosis, Transthyretin gene silencing is an emerging treatment strategy. However, a recent study has found Eplontersen to be effective in improving neuropathy and life quality among adults with ATTRv polyneuropathy. Eplontersen treatment group had lower serum transthyretin concentration than the historical placebo, Says Teresa Coelho, MD, PhD, in an original investigation published in JAMA.

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In this open-label study, Researchers evaluated eplontersen in ATTRv polyneuropathy. They enrolled patients, out of which 144 patients (mean age 53) were assigned to subcutaneous eplontersen and 60 (mean age 59) were assigned to historical placebo group. Interventions included the administration of Subcutaneous eplontersen 45 mg every four weeks. A small reference group of 24 patients received subcutaneous inotersen 300 mg weekly and subcutaneous placebo weekly in NEURO-TTR.

NEURO-TTRansform was an open-label, single-group, phase 3 trial conducted across 15 countries, including 168 adults with Coutinho stage 1 or 2 ATTRv polyneuropathy. Patients treated with a placebo from NEURO-TTR, an inotersen trial with similar eligibility criteria and endpoints, served as a historical placebo (“placebo”) group.

Primary efficacy endpoints at week 65/66 were changes from baseline in serum transthyretin concentration, modified Neuropathy Impairment Score +7 composite score and Norfolk Quality of Life Questionnaire–Diabetic Neuropathy (Norfolk QoL-DN) total score.

Key results of the study are:

  • 144 patients in the eplontersen group and 52 in the placebo completed 66-week follow-up.
  • At week 65, the adjusted mean percentage reduction in serum transthyretin in eplontersen and placebo was −81.7% and −11.2%, respectively, with a difference of −70.4%.
  • Adjusted mean change from baseline to week 66 was lower (better) with eplontersen vs. placebo for mNIS+7 composite score and Norfolk QoL-DN with a difference of -24.8 and −19.7, respectively.
  • Adverse events by week 66 causing study drug discontinuation occurred in 6 and 2 patients in the eplontersen and placebo groups, respectively.
  • Through week 66, 2 deaths were reported in the eplontersen group.
  • No deaths reported in the placebo group.

In patients with ATTRv polyneuropathy, the eplontersen treatment group demonstrated changes consistent with significantly lowered serum transthyretin concentration, less neuropathy impairment, and better quality of life than a historical placebo.

Reference:

Coelho T, Marques W, Dasgupta NR, et al. Eplontersen for Hereditary Transthyretin Amyloidosis With Polyneuropathy. JAMA. Published online September 28, 2023. doi:10.1001/jama.2023.18688


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Article Source : JAMA

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