AstraZeneca, Moderna pen deal for mRNA heart failure drug

AstraZeneca and Moderna Therapeutics have agreed to codevelop a relaxin mRNA treatment for heart failure. The candidate is designed to induce the body to produce relaxin, a hormone research groups including Novartis see as a way to regulate the conditions that exacerbate heart failure. 

Moderna has advanced the candidate, AZD7970, through discovery and to the point it is ready to become the eighth therapeutic asset in its pipeline. That done, Moderna has turned to long-time partner AstraZeneca to plot a path through development that taps into the companies’ respective strengths.

Cambridge, Massachusetts-based Moderna is running the first leg. Once the deep-pocketed biotech has put AZD7970 through IND-enabling toxicology tests, AstraZeneca will take over for early clinical trials. If those trials go well, AstraZeneca and Moderna will share the cost of late-stage development and evenly split any profits the drug makes in the U.S. AstraZeneca will handle commercialization outside of the U.S. and pay Moderna tiered royalties up to “substantial double digits.”

The partners’ commitment to the relaxin program comes six weeks after they posted early clinical data on their existing cardiac program, AZD8601. That candidate encodes for vascular endothelial growth factor (VEGF-A), a protein that induces the growth of blood vessels. 

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AstraZeneca has filed to test the VEGF-A asset in heart failure patients undergoing cardiac bypass grafting surgery in phase 2a and now has one eye on the next piece of its mRNA cardiovascular plans, AZD7970.

AZD7970 differs from AZD8601 in terms of both the protein it encodes for and its formulation. The candidate is the second in Moderna’s public pipeline to use N2GL, a proprietary formulation the biotech thinks will enable repeat, systemic dosing. 

In the case of AZD7970, Moderna hopes these doses will induce production of relaxin. This peptide hormone is linked to a range of hemodynamic and renovascular changes that could help patients with heart failure, including vasodilation and the production of VEGF. 

Moderna’s approach is an mRNA-enabled twist on an idea pursued by other research groups. Novartis took its recombinant form of relaxin, serelaxin, as far regulatory filings on both sides of the Atlantic in 2014, only to receive rejections in both territories. The Big Pharma responded with a 6,600-patient phase 3 trial. That study missed its primary endpoint earlier this year.

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Novartis is one of a long list of drugmakers, going back more than a decade, to swing and miss at acute heart failure. News of Novartis’ failure came four months after fellow Swiss drug developer Cardiorentis saw its vasodilator ularitide come up short in phase 3. 

Further back, Abbott, Bayer, Genentech and Merck struggled to make compelling cases for their drugs in phase 2 or 3 acute heart failure trials, despite making big investments to buy and develop pipeline prospects. The drugs included endothelin antagonists, calcium sensitizers and other types of therapeutic. The one thing uniting them is the failure to make a mark in acute heart failure. 

AstraZeneca and Moderna have now placed two bets on the potential for mRNA to succeed where these earlier efforts failed. Given the unproven nature of mRNA therapeutics, the list of thing that could derail AZD7970 is long. But the prevalence of the condition and historic struggles to develop drugs against it mean AstraZeneca and Moderna could be rewarded handsomely if they buck the odds.