New Heart Drugs Look to Revive Profits

"The once lucrative heart-drug market is poised to make a comeback, but at the cost of heavy investments in research and deal making.

After watching lower-priced generics seize sales of once-highflying blood-pressure, cholesterol and other heart drugs, companies struggled to discover replacements and then win reimbursement for five-figure prices. Drugmakers are now rolling out new medicines, though their commercial prospects are uncertain.

Novartis AG recently launched a new cholesterol-lowering therapy bought in a nearly $10 billion deal, while Bristol-Myers Squibb Co. has begun selling a next-generation heart-disease drug that was the centerpiece of a recent $13 billion acquisition.

Alnylam Pharmaceuticals Inc. and Amgen Inc., meanwhile, are working on drugs that silence the defective genes behind some heart conditions.

"We're in a new era," said Steven Nissen, a cardiologist at the Cleveland Clinic. "We have gotten really smart at creating therapies that specifically target what is causing disease."

Pricing has already been a thorny issue. Next-generation cholesterol treatments called PCSK9 inhibitors, which interfere with a protein that makes it difficult for the body to clear bad cholesterol, haven't sold well. The drugs require regular injections, and carry high sticker prices, especially compared with statins such as Lipitor now sold in lower-cost generic versions.

Developing other new heart drugs has been relatively slow. The clinical trials testing the experimental drugs involve more subjects and take longer than studies of cancer therapies, for instance. Also, many of the drugs target heart conditions that are more complex than tumors driven by single-gene mutations.

"Cholesterol issues, blood pressure issues, diabetes, diet, physical activity, behavior -- all these things work together in the background of your genetic predisposition," said Donald Lloyd-Jones, a cardiologist and chief of preventive medicine at Northwestern University's Feinberg School of Medicine in Chicago.

Driving the industry's reinvigorated interest in cardiovascular treatments, however, are a combination of new technologies and better insights into the molecular biology underlying the diseases. And the industry has already seen the potential sales from a robust heart-drugs market

The new products could add $17 billion to the $48 billion worldwide heart-drugs market by 2026, according to Cowen & Co. A next-generation Merck & Co. hypertension treatment could ring up $4 billion in annual sales, while the new Novartis cholesterol-lowering therapy could generate more than $6 billion a year, analysts estimate.

"There is a resurgence in successful development and pipeline presence for cardiovascular disease," said Eliav Barr, chief medical officer at Merck, which acquired its therapy for pulmonary arterial hypertension as part of an $11.5 billion deal last year for the biotech Acceleron. The drug, called sotatercept, is in late-stage testing.

Drugs treating high blood pressure, hypertension and high cholesterol had powered the pharmaceutical industry for decades. Pfizer Inc.'s Lipitor and other cholesterol-lowering statins helped push the cardiovascular drug market to nearly $87 billion in 2010, according to Evaluate, a research firm.

Sales plunged as patents protecting the products ran out and lower-priced generics arrived. Drugmakers shifted focus to other, more lucrative areas, including cancer and autoimmune diseases like rheumatoid arthritis.

Yet physicians say many people aren't well treated by the older drugs and could benefit from new ones. Cardiovascular diseases remain the leading cause of death globally, killing roughly 18 million people annually, according to the World Health Association.

Advances in understanding the role that specific proteins and genes play in diseases provided new drug targets.

Pfizer's Vyndamax was approved in the U.S. in 2019, the first drug cleared for a rare and fatal heart disease caused by the misfolding and clumping of proteins.

Researchers discovered that the plaques of proteins accumulated in the heart, thickening its muscle and interfering with its ability to function. Vyndamax works by reducing the protein buildup, which is known as transthyretin mediated amyloidosis.

The new Bristol drug, Camzyos, treats a different genetic heart disease by blocking a different protein that was found to play a key role in causing the heart muscle to thicken, restricting the organ's ability to pump blood.

Academic researchers discovered the roots of that condition, called hypertrophic cardiomyopathy, in genetic mutations to a protein called myosin. Their findings prompted companies including MyoKardia, which Bristol bought to gain the rights to Camzyos, to develop treatments, according to industry officials.

The advent of the gene-silencing drug technology called RNA interference has also contributed to the development of several new heart medicines. RNA interference, or RNAi, blocks genes from producing proteins found to drive disease.

Alnylam, which helped pioneer the technology, has won regulatory approval in the U.S. to sell RNAi drugs Onpattro and Amvuttra for treatment of the nerve damage caused by protein buildup known as transthyretin-mediated amyloidosis, or TTR. Alnylam is testing the drugs to see if they also work against heart failure caused by the TTR disease.

Research of patients taking the drugs suggests cardiac benefits that could reduce the risk of cardiovascular events, said Pushkal Garg, Alnylam's chief medical officer.

Leqvio, another RNAi drug, interferes with the production of the PCSK9 protein that makes it difficult for the body to clear the bad form of cholesterol known as LDL or low-density lipoprotein, said Victor Bulto, president of innovative medicine at Novartis. Leqvio was developed by Alnylam, which licensed the rights to The Medicines Company, which Novartis later acquired for $9.7 billion.

The Food and Drug Administration approved Leqvio last December in people who have extremely high cholesterol that statins can't control." [1]

1. New Heart Drugs Look to Revive Profits
Hopkins, Jared S. 
Wall Street Journal, Eastern edition; New York, N.Y. [New York, N.Y]. 27 July 2022: B.1.