Amyloidosis, Familial

Dive Brief:Intellia Therapeutics on Thursday released detailed Phase 2 results from a study of a gene-editing therapy for hereditary angioedema, drawing mixed reactions from investors and experts.The therapy, dubbed NTLA-2002, is based on the CRISPR gene editing technology that won a Nobel Prize in 2020. The treatment is designed to inactivate a gene involved in potentially life-threatening inflammatory attacks that plague patients with the disease.In the ongoing study of 27 patients, researchers found either a 75% or 77% reduction in attacks in the 16-week period after receiving therapy, depending on the dose received, Intellia said. And eight of the 11 patients in the higher dose arm were completely free of attacks after a one-time infusion. All of those patients continued to be attack-free with months of followup.Dive Insight:Shares of the company dropped 20% in early trading Thursday, likely because investors were looking for stronger data on the reduction of attacks, Stifel analyst Dae Gon Ha wrote in a note to clients. However, we think fixating on the attack rate reduction misses the bigger picture, which is that NTLA-2002 is a potentially one-time curative therapy.An editorial that accompanied the data, published in The New England Journal of Medicine, agreed. The durability of the therapeutic effect shows promise to last for the patients lifetimes, wrote Kiran Musunuru, a professor at the University of Pennsylvania and co-founder of Verve Therapeutics. We can be confident that NTLA-2002 is helping patients with hereditary angioedema.Investors had been waiting for the details on the study after Intellia announced positive top-line results in August. The latest findings build on early data that showed the therapy could reduce biological markers of the disease. Intellia said its actively screening patients for a Phase 3 trial that will use the higher dose.The Intellia treatment relies on gene editing inside the body, unlike the first-ever approved gene-editing therapy, Casgevy. For that treatment, a patients stem cells are collected, edited and then reinfused to change the patients genetic code. The hereditary angioedema therapy follows Intellias work on a medicine for transthyretin amyloidosis that supported its in vivo approach.Intellia still needs to prove its treatment can work in the Phase 3 trial. And the company will have to make the case to doctors that its worth taking a bet on a one-time, gene-editing therapy rather than the pills or injections that patients have come to depend on to control symptoms. Competitors in the field are also continuing to come up with new options on the more traditional path.Intellia says its hereditary angioedema therapy is safe for patients and offers them the chance to avoid a lifetime of preventive therapy that may not totally relieve symptoms. That possibility is a game changer, according to Paula Busse, a researcher and doctor at Mount Sinai who sees patients with hereditary angioedema and was featured on an Intellia conference call with investors and analysts. '

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.