After Slow Start Entresto Is Poised For Takeoff

–Novartis sees open road to blockbuster status for heart failure drug

After a slow start, the novel heart failure drug Entresto (valsartan/sacubitril) is now poised to become a blockbuster, if drugmaker Novartis’s projections are on target.

The combination pill will record sales of about $500 million in 2017 and may eventually achieve $5 billion in yearly sales in its core heart failure market of HFrEf (heart failure with reduced ejection fraction) patients, the firm believes. That number could double to $10 billion, or mega-blockbuster territory, if the drug is found beneficial in patient populations beyond the current core group.

Despite the dramatic success of the PARADIGM trial and the swift (by FDA standards) approval in the U.S. in July 2015, initial uptake of Entresto was extremely slow. That has now started to change in dramatic fashion, according to Wall Street pharmaceutical analyst Tim Anderson (Sanford Bernstein), who recently reported the details of a lengthy conversation with the outgoing CEO of Novartis, Joe Jimenez, and the incoming CEO, Vas Narasimhan.

The Novartis executives told Anderson that Entresto sales finally began to take off after May 2016, when the U.S. and European guidelines added a strong class 1 recommendation for Entresto. With these guidelines payors lowered their previous high barriers to reimbursement.

Jimenez and Varasimhan said Entresto is set to earn about $500 million this year and has a “steady flow of new patients” indicating that the drug “will continue to grow nicely over the next 3-5 years, even if we did nothing. That is because as heart failure patients are diagnosed, they are going onto Entresto – it is a dynamic cycling of patients onto this drug that is not going to stop.” They said the drug has a trajectory similar to Diovan (valsartan), which reached peak sales of $6 billion a year. They also believe that their recent push in primary care may take a few years to pay off but will eventually lead to “exponential growth.”

The executives said that uptake of Entresto in Europe was slightly better than in the U.S. In both cases new prescriptions are coming from new patients on ACE inhibitors or ARBs “going onto Entresto.” In addition, after being hospitalized for heart failure patients are starting to be discharged on Entresto. “The big opportunity remains to switch patients who have stable disease – there, the physician must be motivated… and this takes time.”

The executives were unconcerned about competition, since there are no current trials with other drugs that could threaten their position. Although there are trials with the SGLT1/SGLT2 drugs, exploring the finding in EMPA-REG of reduced hospitalization for heart failure, “those trial designs put the SGLT2 on top of optimal care (like an ACE/ARB/ARNi) so we don’t see that as a competitive threat.”

A major opportunity to expand eligibility for the drug could be provided by the ongoing PARAGON-HF trial, which is studying Entresto in heart failure with preserved ejection fraction (HFpEF) patients. An interim analysis will occur in the second half of 2018 but “we expect that this trial will have to go to the end. But you never know.” They of course remember that PARADIGM was stopped two years early because of a significant mortality benefit. The HFpEF market is similar in size to the HFrEF market. Overall they estimate there are about 6 million heart failure patients in the U.S. and 8 million in Europe.

Related reading:

• Debate: Switching From Standard HF Therapy To Entresto
• Entresto Gets Boost in Updated HF Guidelines
• Slow Start For ‘Blockbuster’ Heart Failure Drug Entresto
• PARADIGM Investigators Estimate Entresto Prolongs Life by 1-2 Years
• Slow Start For New Novartis Heart Failure Drug Entresto
• New Heart Failure Drug Struggles To Find Its Footing
• Novartis Announces Enormous Clinical Trial Program For Heart Failure Drug
• New Cardio Drugs Off To Very Slow Start
• Top HF Expert Decries ‘Unbelievable Folly’ of Clinical Trials and Guidelines