Ionis Pharmaceuticals has asked the European Medicines Agency (EMA) to approve its lead drug candidate inotersen to treat hereditary TTR amyloidosis (ATTR), also known as familial amyloid polyneuropathy (FAP).
The request, known as a Marketing Authorization Application (MAA), is supported by positive data from the Phase 3 NEURO-TRR trial, and will be given an accelerated review by the EMA.
Ionis is also planning to make a similar request of the U.S. Food and Drug Administration (FDA) this month, submitting what is known as a New Drug Application (NDA). The agency has already designated inotersen an orphan drug as a rare disease potential treatment, and placed it on fast track, or accelerated review, once the NDA is filed and accepted.
“The submission of the inotersen MAA to the EMA represents a critical milestone for Ionis and for European patients suffering from ATTR,” Sarah Boyce, chief business officer of Ionis Pharmaceuticals, said in a press release. “Submission to the EMA puts us one step closer to our goal of fundamentally changing the treatment landscape for patients and families globally who are facing this devastating, progressive, fatal disease, and for the healthcare professionals who treat them.”
ATTR is caused by the accumulation of transthyretin protein, or TTR, in several tissues and major organs. Genetic mutations in the TTR gene result in the protein buildup as fibrils in tissues, damaging them and ultimately leading to organ failure.
Inotersen, also known as IONIS-TTRRx, is a compound designed to reduce the production of TTR to treat this population of patients.
The compound’s safety and efficacy was evaluated in the pivotal Phase 3 NEURO-TTR trial (NCT01737398). The study included 172 patients across 24 clinical sites, who randomly received weekly subcutaneous injections of inotersen at 300 mg, or a placebo, for up to 15 months.
Specifically, at the trial’s end, treated patients reported an 11.68 point difference in the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN) score compared to the placebo group. Half also showed better scores in this quality of life measure over study’s start or baseline.
Inotersen-treated patients also showed a significant 19.73 point benefit on the modified Neuropathy Impairment Score +7 (mNIS+7) — a measure of disease control — compared to placebo.
These beneficial effects were found to be independent of disease severity (stage 1 or 2), TTR gene status (mutated or normal), and previous treatment with alternative therapies.
The most serious treatment-related adverse effects reported were low blood platelet counts (thrombocytopenia) and renal dysfunction. But these side effects were manageable and resolved, researchers said, with no cumulative toxicities due to long-term exposure being reported.
“Therapeutic options for the treatment of hereditary ATTR are very limited and include liver transplant for early-stage patients,” said Teresa Coelho, a neurologist and neurophysiologist at Santo António Hospital, Porto, Portugal. “I am encouraged by the results from the Phase 3 NEURO-TTR study with inotersen, which demonstrated substantial benefit in both quality of life and neurological function for inotersen-treated patients compared to placebo-treated patients.”
Ionis announced that it is in discussions with potential marketing partners regarding the potential commercial marketing of inotersen.
“TTR amyloidosis is devastating, not only for patients but also for caregivers and family members. We are grateful that today we are closer than ever to having an effective treatment to fight this disease,” said Eric Low, head of global strategy with the Amyloidosis Research Consortium UK.