BioPharma, Policy

Why is biosimilar adoption slow in the U.S., and can something be done to boost uptake?

Although the pathway for biosimilars has existed nearly a decade, adoption has lagged behind Europe. Interviewed experts pointed to physician education and the market's immaturity as significant factors.

Since the Hatch-Waxman Act of 1984 created an abbreviated regulatory approval pathway for generic pharmaceutical drugs in the U.S., generics have made tremendous strides in bringing down the cost of many medical treatments and even come to dominate some therapeutic areas.

However, the adoption of biosimilars has so far lagged in comparison to Europe, leading to calls from some rethink to rethink how they’re developed and marketed, with a variety of views on why the U.S. has remained behind its counterparts on the other side of the Atlantic. In two op-eds published in The Wall Street Journal in August, experts argued over whether it was time for Congress to help out the biosimilar industry by making it easier to compete or to simply give up on biosimilars altogether.

The battle of WSJ op-eds began on Aug. 21, when Memorial Sloan Kettering Cancer Center drug pricing expert Dr. Peter Bach and MIT researcher Mark Trusheim suggested, provocatively, that it was “time to throw in the towel” on biosimilars. They wrote that biosimilars’ failure to bring down prices through competition – due to challenges like the need to subject them to clinical trials – meant it would make more sense for Congress to step in and regulate the prices of branded biologics after their market exclusivity periods had passed.

Five days later, former Food and Drug Administration Commissioner Scott Gottlieb wrote that Congress should instead pass laws to increase competition, such as by making it easier for biosimilar makers to securely obtain originator biologic product samples, cracking down on rebates between drugmakers and pharmacy benefit managers and improving physician education.

The op-eds came at a time when biosimilars have faced challenges proving themselves for the U.S. market. In Europe, the introductions of biosimilars have yielded reductions in price-per-treatment-day ranging from 3 percent in oncology to 39 percent for granulocyte colony-stimulating factors, according to a report prepared last year by IQVIA for the European Commission.

Things haven’t progressed as much in the U.S. Since Congress created a pathway for biosimilars in 2010, the Food and Drug Administration has approved 23 of the drugs for treating autoimmune diseases, cancers and side effects of chemotherapy, but only a few have actually hit the market. Nor has those drugs’ presence on the market brought down the cost of biologics, which – as Bach and Trusheim noted – account for 37 percent of drug spending despite making up only 2 percent of dispensed prescriptions.

As it stands, only a small number of biosimilars have actually become available, despite nearly two dozen securing FDA approval. It was only in July, for example, that Amgen and Allergan – under a partnership – launched the first anticancer biosimilars, Mvasi (bevacizumab-awwb) and Kanjinti (trastuzumab-anns), respectively follow-on versions of Roche’s Avastin and Herceptin. Biosimilars of Johnson & Johnson’s rheumatology drug Remicade (infliximab) and supportive-care drugs used to stimulate red and white blood cell growth in patients on chemotherapy – Amgen’s Epogen (epoetin alfa), Neupogen (filgrastim) and Neulasta (pegfilgrastin) – have had more time on the market.

Experts said a number of issues explain why the number of biosimilars launched and adopted by physicians hasn’t kept up with the pace of FDA approvals.

“Biosimilar uptake is not one issue,” said Anita Burrell, a Flemington, New Jersey-based pharmaceutical industry consultant, in a phone interview. “It’s at least four issues in the U.S., and each one contributes to why we don’t have great sales, why we don’t have great savings.”

Some of those issues are the same ones that Gottlieb cited, particularly on the education front.

Other issues, Burrell said, include the fact that the U.S. was several years behind Europe in adopting a regulatory pathway, while the American legal system makes knocking down patents more challenging than in Europe. The way pricing and reimbursement happens in the U.S. – with its patchwork of private and public health systems, as compared with nationwide universal healthcare systems in Europe – creates another challenge.

One example is AbbVie’s rheumatology drug Humira (adalimumab), the Chicago-based drugmaker’s top-selling product. Although four Humira biosimilars now have Food and Drug Administration approval, none can be launched because the patents haven’t expired, and the biosimilar makers have agreed to delay launch in order to avoid costly patent litigation. By contrast, multiple biosimilars of Humira are on the market in Europe.

“So for four more years, we will not have biosimilars of Humira, even though four are already approved,” said Dr. Jonathan Kay, a rheumatologist at the University of Massachusetts in Worcester, in a phone interview. Biosimilars of another rheumatology drug, Amgen’s Enbrel (etanercept), also won’t appear on the market for a few years, also because patents have not yet expired.

Such delays have long been a feature of the generics market. Deals between branded small-molecule manufacturers and generics makers to hold off on launch until after the expiration of market exclusivity but ahead of patent expiry in exchange for avoiding costly patent litigation have been going on for years. But that also restricts the number of biosimilars available and delays the U.S. market realizing their full potential to bring down costs.

“The point about biosimilars is, it’s not the first one that makes the savings – it’s usually the second or third,” Burrell said.

In therapeutic areas that have had a relatively long time to mature, this has already started to happen, notably among supportive-care drugs in oncology.

Dr. Gary Lyman, an oncologist at Seattle’s Fred Hutchinson Cancer Research Center, divided oncology biosimilars into two buckets: supportive care drugs used to treat the side effects of chemotherapy and anticancer agents. Although the first anticancer drugs have only been on the market for a couple of months, supportive care agents have been around much longer.

“The biosimilars to those products have been out on the market for three to four years, and there is indication of price reductions there, and the uptake of those has been quite noticeable,” Lyman said in a phone interview.

In a paper presented at the National Comprehensive Cancer Network’s 2019 annual conference and published in the NCCN’s journal, Lyman pointed out that while data on early adoption of biosimilar hematopoietic growth factor products is limited, one estimate is that biosimilars of Amgen’s Neupogen account for about 50 percent of the U.S. filgrastim market. In the phone interview, Lyman said biosimilars of that drug have brought down costs by around 10 percent.

To be sure, that’s a clear indication that biosimilars can lower costs, but it’s still small potatoes compared with their impact on the European market.

Kay noted that in Sweden, which has a winner-take-all tender process, the availability of biosimilars of Humira prompted AbbVie to reportedly offer a large discount and subsequently win the tender. Thus, even though the biosimilar manufacturers lost, their presence still brought overall costs down. Burrell pointed out that in her native U.K., biosimilars of Humira were able to save NHS England 300 million pounds, or $372.8 million.

That disparity points to some of the market access challenges in the U.S.

“The pricing and reimbursement in this country is like a smoke-and-mirrors game,” Burrell said, adding that it was in the U.S. that she first heard the industry joke that AWP – average wholesale price – stands for “Ain’t What’s Paid.”

But while European countries’ pricing and reimbursement processes are more transparent than the U.S., Burrell said it’s also a matter of getting people on board.

“We have not done the education to get physicians and patients behind it,” she said.

That sets biosimilars apart from generic small-molecule drugs, where such education is largely unnecessary, said Chris Mikson, who heads the FDA practice at the law firm Mayer Brown, in a phone interview. That’s because generics are considered interchangeable with their reference products, and state substitution laws mandate their use when available.

“With generics, you don’t have to market at all,” Mikson said in a phone interview. “The small molecule generic drugmaker doesn’t have to hire a sales force to go convince doctors that the safety and efficacy profile are the same.”

Studies of biosimilars’ use in the clinic have pointed to hesitation among physicians. A study in which Lyman participated, published in the American Journal of Managed Care in June about gaps in oncologists’ use of biosimilars, pointed out that while global sales of biosimilars are expected to reach $19 billion by 2023, physicians have appeared wary of prescribing the drugs, with more than half reporting unfamiliarity with them and more than one-third saying they never prescribed them. In another survey, 30 percent of physicians would not prescribe a biosimilar to a treatment-naive patient.

Ha Kung Wong, an attorney with the New York-based law firm Venable Fitzpatrick, agreed that education of physicians and pharmacists remains a significant barrier. Doctors in particular, may be swayed to switch from a product they know well to biosimilars if those show better efficacy or fewer side effects. But simply showing a cheaper product without offering improvements in safety or efficacy – could end up being a tough sell, especially if the lower wholesale acquisition cost doesn’t translate into lower costs overall.

“I don’t think there’s a whole lot of liability, but there’s a personal obligation we all feel to be comfortable that what we give is the best to offer, and the only factor is not the pricing,” Lyman said. “If efficacy and safety are the same, then price becomes an issue, and efficacy and safety are not as good, we put price on the back burner.”

He added that over time most physicians will just gravitate to whatever is the preferred agent determined by their clinics’ pharmacy and therapeutics committees or patients’ insurance companies. Indeed, insurance companies already seek to nudge people toward lower-cost therapies by putting higher copays on drugs that are not preferred, he noted.

For now, the issue with improving adoption is that there are too few products on the market to motivate physicians to learn about them.

“Healthcare providers have so much learning to do that it’s a matter of prioritization, so are people going to be interested in learning the latest coronary artery disease, or are they interested in biosimilars?” Kay said. “But what compromises that is the lack of biosimilars on the market.”

Photo: Dmitrii_Guzhanin, Getty Images

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