Poikiloderma With Neutropenia

AstraZeneca (AZ) and Ionis’ Wainzua (eplontersen) has been recommended by the European Medicines Agency’s human medicines committee for use in adults with the rare disease hereditary transthyretin-mediated amyloidosis (ATTRv). The Committee for Medicinal Products for Human Use (CHMP) has specifically recommended that the drug be used to treat patients with stage one or two polyneuropathy (PN), a condition that affects multiple nerves in the body and causes pain, progressive weakness and loss of sensation in the legs and arms, as well as mobility difficulties. Up to 40,000 people worldwide are living with ATTRv-PN. Both hereditary and non-hereditary forms of transthyretin (TTR) amyloidosis occur when TTR protein builds up as fibrils in tissues and interferes with their normal functions. As the TTR protein fibrils accumulate, more tissue damage occurs and the disease worsens. Wainzua, which can be self-administered monthly via an auto-injector, is designed to lower the production of TTR protein at its source in the liver. The CHMP’s decision on the therapy was based on positive results from the late-stage NEURO-TTRansform trial, in which Wainzua-treated patients demonstrated consistent and sustained benefit on the co-primary endpoints of serum TTR concentration and neuropathy impairment compared to an external placebo group. Wainzua was also associated with improvements in the key secondary endpoint of quality of life, and the drug continued to show a favourable safety and tolerability profile throughout the trial. The European Commission will now consider the CHMP’s recommendation as it makes a final decision on Wainzua in this indication. Ruud Dobber, executive vice-president, biopharmaceuticals business unit, AZ, said: “Due to the progressive nature of ATTRv-PN, it is critical to have timely diagnosis and new therapies to help people have greater control over this potentially fatal disease. “[This] recommendation brings Wainzua one step closer for patients in Europe, and if approved, will offer a new treatment option that can provide consistent TTR suppression and results in improved quality of life.” The positive opinion comes just days after the Medicines and Healthcare products Regulatory Agency approved Wainzua to treat ATTRv-PN. The US Food and Drug Administration also authorised the drug under the brand name Wainua for the same patient population in December last year. AZ and Ionis are commercialising Wainua for ATTRv-PN in the US, while AZ will develop and commercialise it in the rest of the world, except in Latin America.

ATTRv-PN is a progressive disease that causes peripheral nerve damage and motor disability. Credit: Olena Yakobchuk/Shutterstock. The European Union’s Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of AstraZeneca and Ionis Pharmaceuticals ’ Wainzua (eplontersen) to treat hereditary transthyretin-mediated amyloidosis in adults with stage one or two polyneuropathy (ATTRv-PN). ATTRv-PN is a progressive disease that causes peripheral nerve damage and motor disability, typically leading to death within a decade if untreated. Wainzua’s potential approval by the European Commission would make it the only self-administered, monthly treatment via an auto-injector for ATTRv-PN in the EU. AstraZeneca and Ionis Pharmaceuticals are collaborating on the commercialisation of Wainzua following a global agreement established in December 2021. AstraZeneca holds exclusive commercialisation and development rights in regions outside the US. AstraZeneca bioPharmaceuticals business unit executive vice-president Ruud Dobber stated: “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. See Also: Gilead and MSD to advance once-weekly HIV treatment to Phase III Editas and Genevant team up to develop gene editing therapies “Today’s recommendation brings Wainzua one step closer for patients in Europe, and if approved, will offer a new treatment option that can provide consistent TTR [transthyretin] suppression and results in improved quality of life.” The CHMP’s recommendation is based on results from the NEURO-TTRansform Phase III trial, which demonstrated consistent and sustained benefits in patients treated with Wainzua over 66 weeks. The trial focused on co-primary endpoints of serum TTR concentration and neuropathy impairment, along with a key secondary endpoint assessing the quality of life. Wainzua’s safety and tolerability were also favourably noted throughout the trial. It works as a once-monthly silencer that suppresses serum TTR production at its source in the liver and is designed to treat all kinds of ATTR. The US Food and Drug Administration approved Wainzua for ATTRv-PN treatment in December 2023 under the brand name Wainua, and additional global approvals are being sought. Eplontersen has received orphan drug designation in both the US and the EU to treat ATTR.

AstraZeneca (AZ) has received approval from the Medicines and Healthcare products Regulatory Agency (MHRA) for the use of Wainzua (eplontersen) in adults with the rare progressive condition hereditary transthyretin amyloidosis (ATTRv). The drug has been specifically authorised for use in patients with polyneuropathy (PN), which is damage to multiple nerves outside of the brain and central nervous system. This results in pain, progressive weakness and loss of sensation in the legs and arms, as well as mobility difficulties. In both hereditary and non-hereditary forms of transthyretin amyloidosis, transthyretin (TTR) protein builds up as fibrils in tissues and interferes with their normal functions. As the TTR protein fibrils accumulate, more tissue damage occurs and the disease worsens. Administered as an injection under the skin using a pre-filled pen, Wainzua is designed to lower the production of TTR protein at its source, reducing the effects of the disease. The MHRA’s decision on the therapy was supported by positive results from the late-stage NEURO-TTRansform trial, in which Wainzua-treated ATTRv patients experienced greater reductions in TTR levels and less worsening of the disease from baseline compared to an external placebo group. Julian Beach, MHRA interim executive director of healthcare quality and access, said: “We’re assured that the appropriate regulatory standards of safety, quality and effectiveness for the approval of this new formulation have been met. As with all products, we will keep its safety under close review.” AZ gained access to Wainua in 2021 after signing a global development and commercialisation agreement with Ionis Pharmaceuticals. The agreement outlined that the companies will jointly develop and commercialise the therapy in the US, while AZ will develop and commercialise it in the rest of the world, except in Latin America. The partners received US Food and Drug Administration approval for Wainua to treat ATTRv-PN in December last year. Ruud Dobber, executive vice president, biopharmaceuticals business unit, AZ, said at the time of the announcement: “There is an urgent medical need for new therapies for people living with [ATTRv-PN]. The US approval of Wainua offers a new treatment option that provides consistent and sustained reduction in serum TTR concentration compared to baseline while halting disease progression and improving quality of life for people living with this debilitating condition.”