Heart Failure Health Area Wide Open for New Therapeutics

Heart failure is an underserved health area that is continuing to grow. Decision Resources Group recently estimated it will expand from $2.9 billion in 2013 to $8.9 billion in 2023. Breakthroughs have been limited for some years, so the field is wide open for promising therapeutics.

"Heart failure is very common and getting more common, very expensive in terms of co-morbidities and really underserved," says Les Funtleyder, a healthcare portfolio manager at E Squared Asset Management and member of Pharm Exec's Editorial Advisory Board.

Few drugs are generating more enthusiasm than Novartis' heart failure and hypertension treatment LCZ696. The drug has novel mechanisms, combining sacubitril to preserve peptides that lower blood pressure and valsartan to improve vasodilation. There haven't been any major improvements in heart failure therapies in decades. EvaluatePharma puts sales at $1.3 billion by 2020, while Thomson Reuters has them at $1.8 billion in 2019. Both estimates may be conservative.

Data from a pivotal Phase III trial showed the drug reduced the risk of death by 20%, compared to an angiotensin-converting-enzyme (ACE) inhibitor, as well as dramatically reducing the risk of hospitalization. There's a lot of excitement that this new drug could supplant ACE inhibitors and ARBs.

"We're forecasting $6 billion of peak sales, but that number could be low by a factor of 50% or even a 100%," says Seamus Fernandez. "LCZ696 could be a Plavix-like product."

This enthusiasm appears to be widespread. "LCZ696 has been described as a game changer and there are some that believe that because of its mortality benefit it should become the standard of care replacing ACE inhibitors and ARBs, especially given its very clean safety profile," says Urquhart. "The market was also quick to wake up to its potential and after the Paradigm-HF trial was stopped early in March because of its conclusive benefits."

By contrast, Novartis' other heart failure drug has hit hard times. In May this year, the FDA rejected Novartis' biologics license application (BLA) for Serelaxin. A synthetic human relaxin 2 hormone, Serelaxin has breakthrough designation but the FDA needed more efficacy data for approval and had issues with the trial design. Novartis has been conducting a large Phase III trial and hopes the results, expected in 2016, will sway the FDA.

Serelaxin is a tantalizing prospect for both Novartis and analysts. In addition to the potential one-two punch with LCZ696, acute heart failure is a serious unmet need, with clinicians looking for successors to beta blockers, developed in the 1960s, and ACE inhibitors, developed in the '80s.

"There hasn't been a product to advance the in-hospital treatment for heart failure in somewhere between 30 and 50 years," notes Fernandez.

Fernandez styles Serelaxin a dark horse. However, if Novartis can get past the regulatory hurdles, Leerink Partners projects Serelaxin could be worth two to three billion dollars. By contrast, EvaluatePharma puts its sales at $484 million by 2018.