AstraZeneca's $700M+ In-Licensed Therapy for Fatal Cardiomyopathy Granted Clinical Trial Approval in China

▎Edited by the WuXi AppTec content team

Screenshot source: CDE official website

ATTR-CMIt is a systemic, progressive, and fatal disease that can lead to progressive heart failure and death in patients. ATTR-CM patients experience aging or gene mutations, resulting inATTR misfolding and deposition as amyloid fibrils in the myocardium, thereby damaging the normal function of the corresponding organs and tissues, and ultimately leading to death. Although treatments for this disease have been approved, these therapies can only prevent the accumulation of amyloid proteins, and have no effect onModerate to severe ATTR-CM patients with extensive amyloid deposition in the heart, they still face significant unmet needs.

ALXN2220Is a research-stage humanized monoclonal antibody, specifically designed forPhagocytic Immune Cells Clear ATTRAnd development. The product canSpecifically targets misfolded transthyretin, and by clearing amyloid fibril deposits in the heart, addresses the pathological cause of ATTR-CM, offering hope for treating patients with advanced ATTR-CM.Preclinical models have shown that the product can induce the clearance of pathological ATTR.

In March 2022, Alexion announced the completion of its collaboration with Neurimmune onALXN2220AchievedExclusive Global Collaboration and Licensing AgreementAccording to the terms of the agreement, after the completion of the Phase 1 clinical trial, Alexion will be responsible for further clinical development and commercialization of the candidate therapy.Neurimmune to Receive $30 Million Upfront Payment and Up to $730 Million in Development, Regulatory, and Commercial Milestone Payments.

June 2023,ALXN2220 TreatmentPhase 1 Clinical Study of ATTR-CM Published in The New England Journal of Medicine.In this phase 1, double-blind trial, researchers randomly assigned 40 patients with wild-type or variant ATTR cardiomyopathy and chronic heart failure to receiveALXN2220Or placebo intravenous infusion,Once every 4 weeks, for 4 monthsPatients were sequentially enrolled into six cohorts receiving escalating doses. After four infusions, patients entered an open-label extension phase, during which they received eight infusions.ALXN2220Infusion, gradually increasing the dose.

The research results show that,ALXN2220The safety remained favorable at the highest tested dose, with no evident dose-limiting toxicity or drug-related serious adverse reactions observed. The pharmacokinetic profile of this product is consistent with IgG antibodies, and no anti-drug antibodies were detected.At a dose of at least 10 mg/kg, cardiac amyloid deposition in patients (detected by scintigraphy or cardiac magnetic resonance imaging) was significantly reduced within 12 months.Biomarkers for Measuring Cardiac Pressure and Myocardial Cell DeathLevels of NT-proBNP and troponin T were also reduced.

[2]Pablo Garcia-Pavia. et al. (2023)Phase 1 Trial of Antibody NI006 for Depletion of Cardiac Transthyretin Amyloid.N Engl J Med. DOI: 10.1056/NEJMoa2303765