The cardiovascular scene to shift by 2024 as next-generation drugs like Eliquis and Xarelto eclipse stalwarts

The cardiovascular drug market has seen big developments in recent years, as warfarin and old-line statins have given way to next-generation blood thinners and novel, high-priced cholesterol fighters. 

Drugmakers continue to focus on the CV where they have reaped big rewards with treatments for perpetual conditions like heart disease and hypertension. They expect that to continue as they develop new-generation drugs with novel mechanisms—but higher prices—to replace those CV drugs now facing generic competition. Based on global 2017 numbers from PharmaCompass and Evaluate Pharma, five drugs stand out today in this fiercely competitive field, including mainstays Crestor and Lipitor. However, according to Evaluate Pharma in August, the landscape will look very different in 2024. 

Leading the pack in 2017—and 2024—are two antifactor Xa agents: Bristol-Myers Squibb with Pfizer’s Eliquis and Johnson & Johnson with Bayer’s Xarelto.

Despite being third to market and a slow rampup during early days, Eliquis overtook Xarelto as the most prescribed novel oral anticoagulant (NOAC) in the U.S. in the first quarter of 2017. For the whole year, the drug produced $4.87 billion in sales, up 46% from 2016’s $3.34 billion.

Globally speaking, Xarelto, which returned Bayer and Johnson & Johnson $5.64 billion in 2017 sales, was leading Eliquis, but BMS sees significant momentum and room for Eliquis growth ahead, as the large share held by traditional mainstay warfarin is up for grabs, especially outside the U.S.

According to BMS executives on the 2018 second-quarter earnings call in July, warfarin boasts nearly 40% share of total oral anticoagulant prescriptions, but the gap between it and Eliquis is quickly closing. In fact, according to BMS’ U.S. commercial head Johanna Mercier, the lead could have changed hands already.

RELATED: BMS, Pfizer's fast-growing Eliquis is about to steamroll market-leader warfarin: executive

The growing interest is for the whole NOAC class, including Xarelto. Both Xarelto and Eliquis got a boost in May after the FDA approved Portola’s Andexxa as a bleeding antidote. Before that, the two NOACs didn’t have an approved agent to help reverse bleeding events, while rival Boehringer Ingelheim’s Pradaxa has had one since 2015.

That said, BMS expects Eliquis will keep a leading position against Xarelto as the entire NOAC usage expands, and it probably has real-world results from a large study based on U.S. Medicare patient records to thank. In that analysis, Eliquis displayed lower risks of stroke and major bleeding versus warfarin, while Xarelto and Pradaxa beat only one of those safety measures.

Analysts share BMS’ optimism. According to estimates by Evaluate Pharma, Eliquis’ sales will shoot past $11.3 billion by 2024, nearly double Xarelto’s projected $5.8 billion.

RELATED: From old behemoth Lipitor to new king Humira: Best-selling U.S. drugs over 25 years

Crestor, a statin marketed by a partnership of AstraZeneca, Shionogi and Chiesi in different parts of the world, came up third, with 2017 sales of around $2.7 billion. That was after generic versions that hit key markets around the world eroded nearly 30% off its sales year over year. That free fall extended into 2018, as the $727 million AZ reported for the first half of the year represented a 39% decline, despite China turning in a strong performance, with $238 million in sales. Crestor’s sales peaked in 2011.

Another megablockbuster statin, Pfizer's Lipitor, has had a great run since it reached the market in 1996, having helped Pfizer collect nearly $95 billion in global sales. Even in 2017, six years since it went off patent, the branded drug registered small growth for Pfizer and its global partners, coming in at $2.16 billion in sales, standing as the year’s fourth-best-selling CV drug. Evaluate analysts predicted it will produce $1.85 billion in 2024.

Another example of an old powerhouse holding some ground in the face of generics lies in Sanofi’s Plavix. The antiplatelet, approved by the FDA in 1997, raked in about $1.7 billion for Sanofi last year, though that was way below its peak before generics flooded into the U.S. in 2012.

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By 2024, Crestor, Lipitor and Plavix will yield their positions to newer drugs, Amgen’s PCSK9 inhibitor Repatha, Novartis’ Entresto and Johnson & Johnson’s Uptravi per Evaluate’s estimates.

The new-generation cholesterol-fighter Repatha has had a slow start since hitting the market 2015. In 2017, the cholesterol drug only generated $333 million for Amgen and partner Astellas. Last December, it won a much-needed FDA approval and is now able to boast its ability to cut the risks of heart attacks and strokes. Still, Bernstein’s analysts have said they “do not expect much commercial impact,” suspecting that its CV benefit isn’t big enough to warrant its cost.

But things started heating up in the first quarter of 2018, when Repatha brought in sales of $123 million, compared to a disappointing $98 million in the previous quarter. That sequential growth continued in the second quarter as sales reached $148 million, despite payer restrictions.

Evaluate expects Repatha sales will steamroll to $4.26 billion in 2024. But to get there, it faces in-class competition from Sanofi and Regeneron’s Praluent, which turned up its own CV benefit data in March and lowered Paluent’s price to cut a formulary deal with Express Scripts.

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Novartis’ heart failure drug Entresto experienced a similar path that initially didn’t quite live up to its blockbuster expectations. Last year, a new analysis of data from the pivotal trial showed that diabetes patients taking Entresto had a higher drop in HbA1c than those on enalapril. In addition, favorable clinical guidelines from the American College of Cardiology also helped remove some payer roadblocks.

Those advancements helped Entresto surpass $500 million in 2017 sales. By 2024, Evaluate thinks global sales from the drug can reach $4.07 billion.

Apart from Bayer-partnered Xarelto, Johnson & Johnson also owns two pulmonary arterial hypertension drugs through its Actelion buyout. Opsumit and Uptravi pulled in $573 million and $536 million globally in 2017. But as Evaluate sees it, by 2024, it is Uptravi that will take the fifth spot on the top-selling CV drugs list, with $1.91 in annual sales, while Opsumit will grow to $1.68 billion.

The top 5 cardiovascular drugs by 2017 global sales ($B)

Drug name Company 2017 WW sales 2016 WW sales
Xarelto Bayer/J&J 5.64 4.99
Eliquis BMS/Pfizer 4.87 3.34
Crestor AZ/Shionogi/Chiesi 2.70 3.87
Lipitor Pfizer/Jeil/Astellas 2.16 2.04
Plavix Sanofi 1.70 1.79

The top 5 cardiovascular drugs by 2024 global sales ($B)

Drug name Company 2017 WW sales 2024 WW sales
Eliquis BMS/Pfizer 4.87 11.31
Xarelto Bayer/J&J 5.64 5.83
Repatha Amgen/Astellas 0.33 4.26
Entresto Novartis/ROVI 0.51 4.07
Uptravi J&J/Nippon Shinyaku 0.54 1.91