Tegsedi Helps Preserve Patient Quality of Life in Extension Study
Long-term treatment with Tegsedi (inotersen) helps preserve quality of life in people with familial amyloid polyneuropathy (FAP) for up to three years, according to data from the Phase 3 NEURO-TTR trial and its extension study.
While patients initially assigned to a placebo stopped experiencing declines in quality of life after switching to Tegsedi in the extension study, they did not attain the same quality of life levels as those who were initially assigned to and remained on Tegsedi.
These findings add to early analyses supporting Tegsedi’s long-term benefits at easing nerve cell damage (neuropathy) symptoms and the importance of early treatment in this patient population, researchers noted.
The study, “Early Data on Long-term Impact of Inotersen on Quality-of-Life in Patients with Hereditary Transthyretin Amyloidosis Polyneuropathy: Open-Label Extension of NEURO-TTR,” was published in the journal Neurology and Therapy.
FAP, also known as hereditary transthyretin amyloidosis, is characterized by the buildup of toxic clumps of the transthyretin (TTR) protein in different tissues and organs, including the heart and nerves.
Over time, these deposits cause damage and disrupt the normal function of these tissues and organs. As the disease progresses, patients’ quality of life, including their ability to engage in everyday activities, socialize with others, work, and live independently, continually worsens.
Developed by Ionis Pharmaceuticals, Tegsedi works by suppressing the production of TTR in the liver, where the protein is mostly produced. Injected once weekly under the skin, the medication is approved for the treatment of adults with FAP in North America, Europe, and other regions.
The therapy’s regulatory approvals were based on results of the Ionis-sponsored Phase 3 NEURO-TTR trial (NCT01737398), which evaluated the safety and effectiveness of 15 months of treatment with Tegsedi against a placebo in 172 adults with FAP.
Data showed Tegsedi lessened patients’ neuropathy symptoms and stabilized or improved their quality of life, compared with a placebo since the study’s start.
Of the 139 patients completing the NEURO-TTR trial, 135 (97%) chose to enroll in its open-label extension (OLE) study (NCT02175004), in which all received Tegsedi for up to five years. Eighty-five continued to receive Tegsedi (Tegsedi group) and 50 switched from placebo to the therapy (placebo-to-Tegsedi group).
Previous two-year data from the combined NEURO-TTR and OLE studies showed that Tegsedi-associated benefits were maintained with longer treatment and that patients switching to the therapy started to experience such benefits.
While these preliminary findings suggest that Tegsedi effectively stabilizes global measures of health-related quality of life (HRQOL), “its impacts on specific aspects of neuropathy-specific and generic HRQOL over this extended duration have not previously been examined,” the researchers wrote.
Now, the scientists have evaluated changes in specific quality-of-life domains over the first two years of the OLE study, totaling up to three years of treatment in the Tegsedi group and up to two years in the placebo-Tegsedi group.
Two patient-reported measures were used: the neuropathy-specific Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QOL-DN), and the generic SF-36v2 Health Survey (SF-36v2).
This interim analysis, with a cut-off date of May 31, 2018, showed that all HRQOL domains previously shown to have stabilized with Tegsedi during the NEURO-TTR study remained generally unchanged during the OLE study.
While these domains worsened for patients given a placebo during the main trial, they stabilized after these patients switched to Tegsedi in the OLE study.
These domains included Norfolk QOL-DN’s activities of daily living, physical functioning, and neuropathic symptoms, as well as SF-36v2’s physical functioning, role-physical, bodily pain, and role-emotional. Bodily pain was reduced in both groups after six months of Tegsedi treatment and maintained thereafter.
In addition, the proportion of patients in the Tegsedi group reporting substantial impairments across a wide variety of symptoms, daily activities, and functioning did not change over time.
These preliminary findings highlight Tegsedi’s efficacy at preserving patients’ quality of life, regardless of previous treatment, for up to two to three years.
Group differences in terms of quality of life at OLE’s start were sustained through two years, but quality of life in the placebo-Tegsedi group “did not improve to match that of patients who received [Tegsedi] during the NEURO-TTR study,” the researchers wrote.
As such, while Tegsedi “can stop further damage from occurring because of new [TTR clumps], it cannot reverse the damage that occurred prior to treatment, including the subsequent impacts of this damage on patients’ quality of life,” the team wrote.
This finding underscores the importance of early diagnosis and treatment in this patient population, while still supporting “later treatment even at more advanced states,” the researchers added.
“Given that previous analyses observed no additional safety concerns or increased toxicity in patients exposed to [Tegsedi] for up to 5 years, [Tegsedi] may be a promising long-term treatment option for these patients,” the researchers concluded.
The release of final five-year data from the OLE study, completed in January, is expected to help confirm Tegsedi’s long-term benefits in FAP patients.