Novo Nordisk Acquires Prothena’s PRX004, Plus Full ATTR Program

Novo Nordisk has acquired Prothena’s clinical-stage antibody PRX004, an investigational therapy for people with hereditary transthyretin amyloidosis (ATTR), which also includes familial amyloid polyneuropathy (FAP), as well as other non-hereditary forms of the disease.

While the company initially will focus on developing PRX004 for the treatment of ATTR cardiomyopathy — a form of the disease that mainly affects the heart — Prothena’s broader ATTR amyloidosis research program also is part of the acquisition deal. That research program includes PRX004 as a treatment for FAP, a disease type that causes nerve damage to the peripheral nervous system, which is the network of nerves found outside the brain and spinal cord.

“With Novo Nordisk’s commitment to further develop PRX004 in ATTR cardiomyopathy, Prothena will continue to focus on our mission to advance our robust portfolio designed to address rare peripheral amyloid and neurodegenerative diseases,” Hideki Garren, MD, PhD, chief medical officer at Prothena, said in a press release.

PRX004 is an antibody-based therapy designed to clear misfolded forms of transthyretin — the protein that clumps together and forms toxic amyloid deposits in all forms of ATTR amyloidosis — without affecting the normal protein.

“With its innovative amyloid-depleting mechanism, PRX004 has the potential to offer a novel treatment option for ATTR cardiomyopathy — an often fatal disease with significant unmet medical need,” said Marcus Schindler, PhD, chief scientific officer and executive vice president of research and early development at Novo Nordisk.

“This acquisition is a testament to Prothena’s pioneering work in ATTR amyloidosis and Novo Nordisk’s dedication to advancing new disease-modifying therapies for the benefit of people with cardiovascular diseases,” Schindler added.

Prothena previously had completed a Phase 1 trial (NCT03336580) evaluating PRX004 in 21 people with hereditary forms of ATTR amyloidosis, including patients with FAP and those with other clinical manifestations. PRX004 was infused into the bloodstream once every 28 days, for up to three times, in the dose-escalation portion of the study.

The experimental therapy was well-tolerated and generally safe at all doses, and no serious adverse events were reported. All of the patients completed the dose-escalation part of the trial, and 17 enrolled in a long-term extension phase.

Evaluable patients experienced a mean increase of 1.29 points in the Neuropathy Impairment Score (NIS) at nine months. That tool measures the extent of nerve damage, with higher scores indicating greater severity. In contrast, untreated patients would expect, on average, an increase of 9.2 points over the same period. Additionally, in three participants, the NIS dropped by a mean of 3.3 points.

Treatment with PRX004 also improved heart function in all participants, as measured by lower global longitudinal strain (GLS) scores, which assess the strain put on heart muscles. Notably, GLS reductions were more prominent in the three patients who saw their NIS points drop during the study.

“We are confident that Novo Nordisk will leverage its extensive expertise in developing treatments for those affected by cardiovascular diseases to advance this promising potential treatment to patients on an expedited timeline,” Garren said.

“We also wish to extend our sincere thanks and appreciation to all the patients and investigators who participated in the PRX004 phase 1 study,” he added.

Under the terms of the acquisition agreement, Novo Nordisk gains full worldwide intellectual property and related rights to Prothena’s ATTR amyloidosis pipeline. In turn, Prothena is eligible to receive development and sales milestone payments totaling up to $1.2 billion.