"The data presented today show the potentially profound benefit that treatment with inotersen may provide to people suffering from hATTR - a devastating and progressive disease that robs people of their independence and dignity," said Dr.
The NEURO-TTR study met both co-primary endpoints, the Norfolk QoL-DN, a validated instrument for physician-assessed quality of life, and mNIS+7, a validated instrument for evaluating hATTR disease severity. Consistent and significant benefit compared to placebo was observed in both co-primary endpoints at both eight months and 15 months. In addition, consistent and significant benefit was observed in both endpoints independent of disease stage, types of mutation, previous use of TTR stabilizers or presence of cardiomyopathy. Compared to placebo-treated patients, inotersen-treated patients experienced substantial and statistically significant benefits, including:
- A mean 11.68-point and a mean 6.14-point benefit compared to placebo in Norfolk QoL-DN at 15 months and eight months respectively (p=0.0006, p=0.032).
- A mean 3.59-point clinically meaningful benefit compared to placebo in the
SF-36 Health Surveyat 15 months (p=0.006). SF-36 is a commonly used and validated QoL instrument for assessing general health status across eight domains of health.
- A mean 19.73-point and a mean 8.69-point benefit compared to placebo in mNIS+7 at 15 months and eight months respectively (p=0.00000004, p=0.0005).
- Encouraging benefit compared to placebo in multiple cardiac measures in patients with significant cardiac disease at baseline (interventricular septum thickness, IVS ≥ 1.5 cm), including left ventricle mass (p=0.0288), IVS (p=0.0150), posterior wall thickness (p=0.0425), and trends in favor of inotersen treatment vs. placebo treatment in global longitudinal strain.
- Significant benefit compared to placebo in patients with cardiac disease at baseline in both primary endpoints (Norfolk QoL-DN, p=0.036 and mNIS+7, p<0.001) and in the
SF-36 Health Surveyendpoint (p=0.025) at 15 months.
Two key safety issues were identified during the study: thrombocytopenia and safety signals related to renal function. Enhanced monitoring was implemented during the study to support early detection and management of these issues. Serious platelet and renal events were infrequent and easily managed with routine monitoring, which has proven effective since implementation. Other serious adverse events were observed in 24.1% of inotersen-treated patients and 21.7% of placebo-treated patients. No cumulative toxicities have been identified with long-term exposure.
Adverse events occurring in ≥10% of patients and twice as frequently in inotersen-treated patients compared with placebo-treated patients, included thrombocytopenia/platelet count decreases, nausea, pyrexia, chills, vomiting and anemia. Injection site reactions accounted for less than 1% of all injections and were mild or moderate in severity. There were no discontinuations due to injection site reactions.
The overall mortality rate in the NEURO-TTR study was 2.9% and was lower than mortality rates reported in other studies in hATTR patients. There was a total of five deaths in the study, five (4.7%) in the inotersen arm and zero in the placebo arm. Four deaths in the inotersen arm were associated with disease progression and considered unrelated to treatment. As previously reported, there was one fatal intracranial hemorrhage in conjunction with serious thrombocytopenia. No serious thrombocytopenia was observed following implementation of more frequent monitoring.
"The results from the NEURO-TTR study support a favorable benefit-risk profile for inotersen in patients with hATTR. We believe inotersen has the potential to give people living with this devastating, progressive, fatal disease new hope and the ability to regain freedom from the burden of their disease," said
Inotersen is an antisense drug designed to reduce the production of transthyretin, or TTR, to treat patients with TTR amyloidosis (ATTR), a severe, rare and fatal disease. In patients with ATTR, both the mutant and wild type (wt), TTR builds up as fibrils in tissues, such as the peripheral nerves, heart, gastrointestinal system, eyes, kidneys, central nervous system, thyroid and bone marrow. The presence of TTR fibrils interferes with the normal functions of these tissues. As the TTR protein fibrils enlarge, more tissue damage occurs and the disease worsens, resulting in poor quality of life and eventually death.
ABOUT INOTERSEN PHASE 3 CLINICAL STUDY
Inotersen completed a Phase 3 study, NEURO-TTR, in patients with polyneuropathy due to hereditary TTR amyloidosis (hATTR) in
Ionis is the leading company in RNA-targeted drug discovery and development focused on developing drugs for patients who have the highest unmet medical needs, such as those patients with severe and rare diseases. Using its proprietary antisense technology, Ionis has created a large pipeline of first-in-class or best-in-class drugs, with over three dozen drugs in development. SPINRAZA® (nusinersen) has been approved in global markets for the treatment of spinal muscular atrophy (SMA). Biogen is responsible for commercializing SPINRAZA. Drugs that have successfully completed Phase 3 studies include inotersen, an antisense drug Ionis is developing to treat patients with hereditary TTR amyloidosis (hATTR), and volanesorsen, an antisense drug discovered by Ionis and co-developed by Ionis and
IONIS' FORWARD-LOOKING STATEMENT
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Ionis Pharmaceuticals Investor and Media Contacts: D. Wade Walke, Ph.D., Vice President, Corporate Communications and Investor Relations, 760-603-274; Alissa Santa Maria, Assistant Director, Corporate Development, 760-603-2643; Jennifer Capuzelo, Assistant Director, Corporate Communications and Investor Relations, 760-603-2606