TTR

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.

Oral presentation at ASN on lead program, ABO-101 for primary hyperoxaluria type 1 (PH1), supporting in vivo proof of pharmacology. On-track for year-end IND/CTA filing.Oral presentation at ALS One and a poster presentation at ESGCT on lead ALS program ABO-202, highlighting in vivo reversal of ALS-associated STMN2 aberrant splicing and phenotypic outcomes in human motor neurons.Poster presentation at ESGCT demonstrating targeted gene knock-in and broader applicability of type V nuclease platform for monogenic diseases. CAMBRIDGE, Mass., Oct. 22, 2024 (GLOBE NEWSWIRE) -- Arbor Biotechnologies, Inc., a biotechnology company discovering and developing the next generation of genetic medicines, today announced oral and poster presentations on pipeline and early discovery programs at upcoming medical and scientific meetings: American Society of Nephrology (ASN) 2024 Kidney Week Meeting, October 23-27 in San Diego, California31st Annual European Society of Gene and Cell Therapy (ESGCT), October 22-25 in Rome, ItalyALS One 7th Annual ALS Research Symposium, November 13-15, Virtual At ASN Kidney Week, Arbor will present in vivo non-human primate (NHP) proof-of-pharmacology data supporting continued development of ABO-101, its most advanced gene editing therapeutic candidate designed to address primary hyperoxaluria type 1 (PH1) through inactivation of the HAO1 gene in the liver. Arbor is on track to file the IND/CTA for ABO-101 in PH1 by year-end. At the ALS One 7th Annual ALS Research Symposium and at ESGCT, Arbor will detail data on its lead ALS program ABO-202, supporting genetic disruption of STMN2, preventing errors in the processing of its mRNA, and elucidating a path towards proof of concept for a therapeutic CRISPR gene editing approach for the treatment of amyotrophic lateral sclerosis (ALS). The company will also showcase novel data at ESGCT demonstrating targeted gene knock-in at an endogenous promoter achieving equivalent or improved knock-in efficiency when compared to type II nucleases. This data supports the efficiency and breadth of applicability of Arbor’s type V nucleases to monogenic diseases. Details for the presentations are as follows: ASN 2024 Kidney Week:Oral Presentation Title: Development of ABO-101, A Novel Gene Editing Therapy for Primary Hyperoxaluria Type 1 Session Date and Time: Thursday, October 24, 2024, 4:30-6:00pm PDT Location: Room 23, Convention Center Presenter: Winston Yan, MD, PhD Abstract Number: TH-OR88 ESGCT 2024:Poster Title: Gene Editing with a Type V CRISPR-Cas Enzyme Disrupting the Aberrant Splicing of STMN2 as a Potential Treatment for ALS Session Date and Time: Poster Session 1, October 22, 7:30-9:00pm CEST Location: Forum, La Nuvola Presenter: Chee Yeun Chung, PhD Abstract Number: P0327 Poster Title: Targeted Knock-In at the Human TTR Locus Using Type V Nucleases Session Date and Time: Poster Session 3, October 24, 2:00-3:30pm CEST Location: Concourse Level 1 and Mezzanine Concourse, La Nuvola Presenter: Whitney J. French, PhD Abstract Number: P0603 ALS One 7th Annual ALS Research Symposium:Oral Presentation Title: Gene Editing with a Type V CRISPR-Cas Enzyme Disrupting the Aberrant Splicing of STMN2 as a Potential Treatment for ALS Session Date and Time: November 14, 3:40-4:00pm EDT Presenter: Priscilla D. Negraes, PhD About Arbor Biotechnologies, Inc.Arbor BiotechnologiesTM, a next-generation gene editing company based in Cambridge, MA, is advancing a pipeline of novel gene editing therapeutics to address a wide range of genetic conditions - from the ultra-rare to the most common genetic diseases. Our unique suite of optimized gene editors goes beyond the limitations of early editing technologies to unlock access to new gene targets and has fueled a robust pipeline of first-in-class assets focused on diseases of high unmet need. We are rapidly advancing our lead program in primary hyperoxaluria type 1 to the clinic and focusing our research and development efforts on genomic diseases of the liver and CNS for which there are no existing functional cures. For more information, please visit: arbor.bio Media Contact:Peg RusconiDeerfield Groupprusconi@deerfieldgroup.com

A US drug pricing watchdog has raised the range by which it thinks Pfizer’s heart muscle disease drug tafamidis, marketed as Vyndamax and Vyndaqel, should be priced annually, but it’s still recommending an 85% to 95% cut, according to a final analysis released this week. The Institute for Clinical and Economic Review (ICER) wrote that the price benchmark for tafamidis, a transthyretin stabilizing agent, should range between $13,600 to $39,000 annually. This final recommendation comes with a higher price than ICER previously released in July , when the organization set the limits between $8,500 and $36,000 per year. Pfizer’s current annual list price is almost $200,000. In a statement to Endpoints News , a Pfizer representative wrote that “the use of QALY as a [clinical effectiveness] measure is well established, however, in rare diseases, this poses some challenges and bias particularly against elderly populations suffering from serious diseases who have a shorter life expectancy and less time to benefit from treatment.” The drug first won approval in 2019, making it the first in the class of drugs to be approved for transthyretin amyloid cardiomyopathy (ATTR-CM), although other competitors are making their way through the development process, like BridgeBio’s acoramidis , which has a PDUFA date set for late November, and Alnylam’s RNA silencing agent Amvuttra (vutrisiran), which was just submitted for an sNDA to the FDA this month. The final price range for Pfizer covers tafamidis and acoramidis, but not Amvuttra “because of the timing of new information on vutrisiran and lack of data needed for modeling,” ICER said.