The primary objective of the OLE study was to evaluate the safety and tolerability of long-term dosing with TEGSEDI. Secondary objectives of the study included understanding progression based on measures such as the modified Neuropathy Impairment Score +7 (mNIS+7) and the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN). Understanding changes over time in generic health-related quality of life based on the Short Form 36
'These data further validate the favorable benefit-risk profile seen in hATTR patients treated with TEGSEDI for their polyneuropathy,' said Louis O'Dea, MB, BCh, BAO. FRCP, chief medical officer of
'The burden of hATTR amyloidosis is significant as patients suffer from progressive neuropathic, gastrointestinal and psychosocial symptoms that can affect every aspect of their lives including the ability to work, take care of their families or participate in everyday activities. Without therapeutic intervention, patient quality of life rapidly deteriorates,' said
hATTR amyloidosis is an under-recognized, debilitating and progressive disease that is caused by the buildup of TTR proteins that misfold due to inherited mutations. It is characterized by the deposition of amyloid fibrils throughout the body including in nervous tissue and can have a devastating impact on patients' quality of life. TEGSEDI is a once-weekly, at-home subcutaneous injection that targets the polyneuropathy of hATTR amyloidosis at its source by reducing production of the TTR protein.
Results from the pivotal, randomized, double-blind, placebo-controlled NEURO-TTR study demonstrated that hATTR amyloidosis patients treated with TEGSEDI experienced significant benefit compared to patients treated with placebo across both co-primary endpoints: mNIS+7, a measure of neuropathic disease progression and the Norfolk QoL-DN. At the end of the study, participants were given the opportunity to enroll in the OLE study and continue treatment with TEGSEDI or switch from placebo. Of the 139 patients who completed the NEURO-TTR study, 135 participants (97%) continued in the OLE study. Among those who participated in the ongoing OLE study, 85 continued to receive TEGSEDI and 50 switched from placebo to TEGSEDI.
No new safety concerns were identified in patients treated with TEGSEDI in the OLE study. There was also no evidence of increased risk for grade 4 thrombocytopenia or acute glomerulonephritis with increased duration of exposure to TEGSEDI. Regular, required platelet and renal monitoring proved to be effective in managing patients' risk. The most common (>10%) adverse events (AEs) include nausea, urinary tract infection, vomiting, diarrhea, fatigue, peripheral edema, injection site pain and thrombocytopenia. Overall, 19 (14.1%) patients discontinued TEGSEDI due to treatment-emergent adverse events (TEAEs). Nine (6.7%) patients died during the OLE study but none of the deaths were considered related to TEGSEDI.
Patients administered TEGSEDI throughout the NEURO-TTR and OLE studies experienced substantial reductions in TTR protein levels (77% reduction on average) compared to their baseline from the NEURO-TTR study. In addition, those treated with TEGSEDI for 39 cumulative months in the NEURO-TTR and OLE studies showed sustained benefit compared to the predicted worsening with placebo. Likewise, those patients who switched from placebo to TEGSEDI demonstrated sustained improvement of neurologic disease progression and quality of life as measured by the mNIS+7, the Norfolk QoL-DN, and the SF-36 Physical Component Summary score (PCS) compared with a continued predicted worsening with placebo. Finally, patients treated earlier with TEGSEDI achieved greater benefit in mNIS+7 (17.06 points) and Norfolk QoL-DN (11.89 points) compared to patients who switched from placebo to TEGSEDI in the OLE study, highlighting the importance of early commencement of TEGSEDI in appropriate patients.
'We are very proud of our role in addressing an area of significant unmet medical need for patients and will continue our efforts to bring TEGSEDI to more patients with the polyneuropathy of hATTR around the world,' said
ABOUT TEGSEDI (INOTERSEN)
TEGSEDI was approved by the
The approval is based on data from the NEURO-TTR study that was a Phase 2/3 randomized (2:1), double-blind, placebo-controlled, 15-month, international study in 172 patients with hATTR amyloidosis with symptoms of polyneuropathy. In NEURO-TTR, TEGSEDI demonstrated significant improvement compared to placebo in measures of neuropathy and quality of life as measured by the modified Neuropathy Impairment Score +7 (mNIS+7) and in the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QOL-DN) total score. Patients treated with TEGSEDI experienced similar benefit regardless of subgroups such as age, sex, race, region, Neuropathy Impairment Score (NIS), Val30Met mutation status, and disease stage.
The approval is also based on early data from the NEURO-TTR OLE that is an ongoing study for patients who completed the NEURO-TTR study. The OLE study is designed to evaluate the long-term safety and efficacy of TEGSEDI.
ABOUT HEREDITARY TRANSTHYRETIN (hATTR) AMYLOIDOSIS
Hereditary ATTR amyloidosis is a severe, progressive, and life-threatening disease caused by the abnormal formation of the TTR protein and aggregation of TTR amyloid deposits in various tissues and organs throughout the body, including in peripheral nerves, the heart and intestinal tract. The progressive accumulation of TTR amyloid deposits in these organs often leads to intractable peripheral sensorimotor neuropathy, autonomic neuropathy, and/or cardiomyopathy, as well as other disease manifestations. Hereditary ATTR amyloidosis causes significant morbidity and progressive decline in quality of life, severely impacting activities of daily living. The disease often progresses rapidly and can lead to premature death. The median survival is 4.7 years following diagnosis.
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As the leader in RNA-targeted drug discovery and development, Ionis has created an efficient, broadly applicable, drug discovery platform called antisense technology that can treat diseases where no other therapeutic approaches have proven effective. Our drug discovery platform has served as a springboard for actionable promise and realized hope for patients with unmet needs. We created the first and only approved treatment for children and adults with spinal muscular atrophy as well as the world's first RNA-targeted therapeutic approved for the treatment of polyneuropathy in adults with hereditary transthyretin amyloidosis. Our sights are set on all the patients we have yet to reach with a pipeline of more than 40 novel medicines designed to potentially treat a broad range of disease, including neurological, cardiovascular, infectious, and pulmonary diseases.
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