Eplontersen approved in UK for FAP; recommended for EU approval
Injection therapy to be sold in Europe under brand name Wainzua
The Medicines and Healthcare products Regulatory Agency (MHRA) in the U.K. has approved the injection therapy eplontersen — under the brand name Wainzua — for treating adults with familial amyloid polyneuropathy (FAP).
Additionally, a European Union regulatory committee has recommended the treatment’s approval in the EU for adults with the disease who have nerve damage that’s a sign of FAP.
The U.K.’s decision follows a similar approval late last year in the U.S., where the therapy, codeveloped by Ionis Pharmaceuticals and Astrazeneca, is sold as Wainua. The medication aims to slow or halt disease progression by suppressing the production of an abnormal form of the transthyretin (TTR) protein that forms the toxic clumps that drive FAP.
The approvals make the FAP therapy the first and only one to be self-administered by patients in both countries via an autoinjector. Treatment is given through under-the-skin, or subcutaneous, injections once a month, at a dose of 45 mg.
“Enabling safe access to high quality, safe and effective medicines is a key priority for us,” Julian Beach, MHRA’s interim executive director of healthcare quality and access, said in an agency press release. “We’re assured that the appropriate regulatory standards of safety, quality and effectiveness for the approval of this new formulation have been met.”
Ionis and Astrazeneca are now working to win Wainzua’s approvals in the EU and other parts of the world, where Astrazeneca holds exclusive commercialization rights to the therapy.
Eplontersen now approved as Wainua in US and Wainzua in UK
In the EU, a committee of the European Medicines Agency recommended Wainzua’s approval for treating FAP patients with stage 1 or stage 2 polyneuropathy, or damage to several nerves outside the brain and spinal cord. Such damage is a marker of FAP.
That decision, by the Committee for Medicinal Products for Human Use, known as CHMP, was welcomed by Ruud Dobber, PhD, executive vice-president of Astrazeneca’s biopharmaceuticals business unit.
“Today’s recommendation brings Wainzua one step closer for patients in Europe,” Dobber said in a company press release, adding that the therapy, “if approved, will offer a new treatment option that can provide consistent TTR suppression and results in improved quality of life.”
People with FAP, also known as hereditary transthyretin-mediated amyloid polyneuropathy (hATTR-PN), have mutations in the TTR gene, which provides instructions for making the TTR protein.
As a result, the body produces an abnormal version of the protein, which forms clumps, known as amyloid fibrils, that build up and damage different tissues, mainly the nerves outside the brain and spinal cord. This causes symptoms like limb numbness, tingling, and weakness.
Wainzua works by binding and blocking TTR’s messenger RNA, an intermediate molecule derived from DNA that acts as a template for protein production. This helps to reduce the production of all forms of the TTR protein and prevent the buildup of amyloid fibrils that damage nerves. Ultimately, the use of Wainzua is expected to slow FAP progression.
“Due to the progressive nature of polyneuropathy of hereditary transthyretin-mediated amyloidosis, it is critical to have timely diagnosis and new therapies to help people have greater control over this potentially fatal disease,” Dobber said.
Therapy aims to slow or halt disease progression in adults with FAP
The newly approved treatment’s mechanism of action is similar to that of Tegsedi (inotersen), an older FAP therapy also developed by Ionis. However, it is modified to boost the drug’s entry into liver cells, the main producers of TTR. This allows Wainzua to be administered less frequently — once a month, compared with once a week — than Tegsedi, which is expected to achieve the goal of reducing the treatment burden for patients.
Laura Obici, MD, of the Amyloidosis Research and Treatment Centre Istituto Di Ricovero e Cura a Carattere Scientifico Fondazione Policlinico San Matteo in Italy, noted that FAP can have “a significant impact on many aspects” of the daily life of patients and caregivers.
“Having additional amyloidosis treatment options designed to reduce the production of TTR protein at its source would potentially give patients more time and ability to do what matters most to them,” Obici said, adding Wainzua offers “the hope of living longer with a higher quality of life.”
The therapy’s approvals were based on data from a global Phase 3 clinical trial called NEURO-TTRansform (NCT04136184), which tested its efficacy and safety in 168 adults with stage 1 or 2 FAP.
Data from this treated group were compared with findings from a placebo group of 60 FAP patients involved in an earlier Phase 2/3 trial (NCT01737398) that had helped to support Tegsedi’s approval.
Relative to the external placebo group, those given Wainua/Wainzua had greater reductions in TTR in their blood after more than a year of treatment. The therapy also eased nerve damage-related disability and improved patients’ quality of life.
Having additional amyloidosis treatment options designed to reduce the production of TTR protein at its source would potentially give patients more time and ability to do what matters most to them. … [Wainzua offers] the hope of living longer with a higher quality of life.
Longer-term results showed Wainua/Wainzua’s therapeutic benefits were mostly sustained through about 1.5 years of treatment.
Given that a decrease in vitamin A in the blood is a common side effect of the therapy, patients starting such treatment are advised to take supplements of the recommended daily allowance of vitamin A, according to Astrazeneca.
Vitamin A deficiency can also cause eye-related issues, including dry eyes and problems seeing at night or in dim light. If people experience these symptoms while on Wainzua, they should inform their physician.
People in the U.K. who experience any side effects from this treatment should consult with medical professionals and report it directly to the MHRA’s Yellow Card scheme.
“As with all products, we will keep its safety under close review,” Beach said of Wainzua.
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