Long-term Tegsedi Therapy Reduces Pain, Improves Quality of Life in FAP

Treatment over 3 years improves physical functioning, trial analysis shows

Somi Igbene, PhD avatar

by Somi Igbene, PhD |

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Long-term treatment with Tegsedi (inotersen) reduced pain and improved physical functioning and health-related quality of life in patients with familial amyloid polyneuropathy (FAP).

That’s according to an analysis of data from the Phase 3 NEURO-TTR trial (NCT01737398) and its open-label extension (OLE) study (NCT02175004).

“Given the significant burden associated with [FAP] on patients and their caregivers, improving HRQL [health-related quality of life] remains a crucial goal to be considered when managing the disease. The data continue to confirm that treatment … preserves functionality and quality of life in patients with [FAP] for more than 3 years,” the researchers wrote.

Findings from the analysis were detailed in the study, “Long-term treatment effects of inotersen on health-related quality of life in patients with hATTR amyloidosis with polyneuropathy: analysis of the open-label extension of the NEURO-TTR trial,” published in the journal Muscle and Nerve.

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Real-world Study: Tegsedi Slows FAP Progression, Preserves Life Quality

FAP, also known as hereditary transthyretin-mediated amyloidosis with polyneuropathy (hATTR-PN), is a rare, inherited, and progressive disease caused by mutations in the TTR gene. These genetic alterations lead to the buildup of toxic protein aggregates or clumps made up of transthyretin (TTR) in different tissues and organs, causing damage.

People with FAP often experience pain, mobility issues, an inability to perform usual daily life activities, and an overall reduction in life quality.

The U.S. Food and Drug Administration (FDA) approved Tegsedi, an agent that blocks TTR production, to treat FAP in 2018. Its approval was supported by data from the multicenter, double-blind, Phase 3 NEURO-TTR trial, which showed Tegsedi was more effective than a placebo at delaying nerve damage and preserving patients’ quality of life.

A double-blind study means that neither researchers nor participants know which patients are receiving the therapy being tested and which are getting a placebo.

Following up on trial data

Findings from the OLE study, completed in 2021, have since shown that Tegsedi can help preserve life quality in people with FAP. But no trial to date has directly assessed the therapy’s long-term effects on pain and physical functioning — two factors that significantly impact well-being and quality of life.

Now, a team of scientists used the Norfolk Quality of Life-Diabetic Neuropahty (Norfolk QoL-DN) and the Short-Form 36 Health Survey (SF-36v2) questionnaires to directly assess the effect of long-term treatment with Tegsedi on pain and physical functioning in people with FAP. All participants had been involved in both NEURO-TTR and its OLE.

The Norfolk QoL-DN is a 35-item self-reporting survey that assesses symptoms of nerve damage and life quality, with higher scores indicating poorer quality of life. The SF-36v2 questionnaire is a 36-item self-reporting questionnaire that measures functional health and well-being. It assesses a range of factors, including body pain, activities of daily living, and mental health.

A total of 172 patients participated in both NEURO-TTR and its OLE. Among them, 112 received Tegsedi consistently during the trial and its OLE, while 60 received a placebo during the trial and Tegsedi during the extension study. Of all participants, 165 had baseline measures and at least one post-baseline pain and physical functioning measurement using the Norfolk QoL DN or SF-36v2 questionnaire.

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Overall, participants initially receiving a placebo had worse life quality scores than those who consistently received Tegsedi. The patients in this non-treatment group experienced greater deterioration over time in pain severity — body pain and “pain that kept them awake at night” — and in their ability to perform daily activities.

In contrast, patients receiving Tegsedi consistently experienced improved life quality and physical functioning, with less severe pain, including body pain and pain that kept them awake at night.

“[Tegsedi] treatment significantly delayed the long-term deterioration of key HRQL outcomes among patients with hATTR-PN, and the benefits were particularly evident for measures related to physical functioning and key pain measures. In some cases, [Tegsedi] treatment was potentially associated with halting or reversal of the decline in HRQL,” the researchers wrote.

The team also noted that “the physical burden becomes increasingly more profound in patients with hATTR as they progress further in the course of the disease.” Thus, this result “underscores the importance of initiating early treatment with effective therapies, such as [Tegsedi], to preserve HRQL,” they wrote.