Novo Nordisk is known for diabetes drugs, but the company has been expanding its scope to adjacent areas, including cardiovascular disease. That strategy continues to play out, and the latest example is a $100 million deal to acquire a rare disease medicine from Prothena in early-stage clinical development.
The Denmark-based pharmaceutical giant announced on Monday an agreement to acquire a drug called PRX004, which Prothena is developing for ATTR amyloidosis, a disease characterized by the abnormal buildup of amyloid deposits in the body. Novo Nordisk plans to focus initially on developing the drug for the buildup of these protein deposits in heart tissue, called ATTR cardiomyopathy.
The $100 million sum is a combination of an upfront payment and near-term clinical milestone payments, the breakdown of which was not specified. Novo Nordisk gains full global rights to PRX004. Depending on the progress of the drug, Prothena could earn up to $1.2 billion for achieving development and sales milestones.
Amyloidosis can stem from the several different types of proteins. In the case of ATTR specifically, it is caused by misfolded transthyretin protein. ATTR primarily affects the nervous system and the heart, and as this buildup worsens, the disease becomes fatal. ATTR is an inherited disorder, though in some cases it is acquired, which is known as wild-type ATTR.
Dublin, Ireland-based Prothena develops drugs that treat protein dysregulation. PRX004 is a monoclonal antibody designed to deplete the amyloid deposits characteristic of both hereditary and wild-type ATTR amyloidosis. According to the company, the drug works without affecting the native, normal form of transthyretin protein. The company said that in preclinical research, the drug promoted the clearance of amyloid by mediating phagocytes, immune cells that ingest harmful bacteria, particles, and cells. The antibody also inhibited amyloid formation, according to the company.
Last December, Prothena released data from a Phase 1 clinical trial testing patients with the hereditary form of ATTR. In this dose-escalation study, patients were given the intravenously infused therapy once every 28 days for up to three infusions. The results showed that the Prothena antibody was safe and well tolerated. Furthermore, of the seven patients that could be evaluated at nine months, the drug demonstrated a slowing of neuropathy progression and showed improvement in the heart’s ability to pump blood. Based on those results, Prothena was preparing to advance PRX004 to a Phase 2/3 study.
Novo Nordisk is trying to expand beyond diabetes, but in a way that builds on its franchise medicines. Type 2 diabetes, obesity, cardiovascular disease, chronic kidney disease, and nonalcoholic steatohepatitis are closely associated, the company said in its 2020 annual report. Semaglutide, the active ingredient in Novo Nordisk diabetes drugs Rybelsus and Ozempic, could apply to cardiometabolic diseases, according to the company. Last year, Novo Nordisk paid $725 million up front to acquire Corvidia Therapeutics, a clinical-stage biotech whose antibody is being developed to reduce the risk of adverse cardiovascular events in chronic kidney disease patients who already have hardening of the arteries and inflammation.
Acquiring the Prothena drug gives Novo Nordisk a chance to compete in ATTR amyloidosis. In 2019, the FDA approved Pfizer’s tafamidis, a capsule, as a treatment for the cardiomyopathy associated with ATTR. The Pfizer drug is designed to bind to transthyretin, preventing it slowing amyloid formation.
Alnylam Pharmaceuticals markets a drug, Onpattro, that is approved for treating ATTR affecting the nerves. The Cambridge, Massachusetts-based biotech’s drug works by stopping a gene from producing the harmful protein, employing a mechanism called RNA interference. That drug is an infusion given every three weeks, though Alnylam is also seeking FDA approval of an injectable RNAi therapy that’s given every three months. Meanwhile, Intellia Therapeutics has early clinical data supporting its experimental gene therapy, which could offer a one-time treatment for ATTR.
The Novo Nordisk deal brings Prothena cash that it can apply to the rest of its pipeline, including its most advanced program, birtamimab, which is still wholly owned by the biotech. That drug in Phase 3 testing in AL amyloidosis, a different form of amyloidosis. Another drug, prasinezumab, is in Phase 2 testing in Parkinson’s disease.
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