IPD Analytics Executive Offers Perspective on Biosimilar Uptake and Policy

The arrival of biosimilars in the United States has followed a winding path, which is the result of initial poor acceptance and, lately, the COVID-19 pandemic, which has gummed up the approval and factory inspections process at the FDA.

But 6 years into biosimilar marketing, it’s possible to see progress and resistance on a more granular level, according to Leslie Fish, RPh, PharmD, vice president of pharmacy at IPD Analytics, who spoke about biosimilars at the Academy of Managed Care Pharmacy (AMCP) Nexus 2021 meeting.

Patent barriers are to blame for some of the wet powder in biosimilar launches, limited physician and payer acceptance are other causes, and the intrusion of COVID-19 priorities at the FDA is another. But aggressive marketing by reference product manufacturers to ward off biosimilar success also can claim a role in slowness of biosimilar acceptance in the United States, Fish said.

“When the pandemic arrived, the first thing that happened was that the clinical trials for biosimilars were delayed or postponed, or actually some even stopped totally. You could not get patients in to see their doctors,” she said.

“The FDA had to take all the people who looked at all the biosimilar data and put them into COVID-19 medication review; but the next thing, which was important for all medications that are in the pipeline, is that the FDA could not get into plants to do manufacturing inspections. In fact, that’s still delayed,” she said.

Not a lot was known about biosimilars 6 years ago when they debuted, Fish said. Biosimilars entered the market at prices much higher than some may have expected. This may have been because people were primed to expect the same thing to happen for biosimilars as happened for generics, which arrived in some cases at discounts of 60% to 70% off the originator brand prices. “It wasn’t near there at all,” she said.

Partly, this was because there was less competition and biologics are costly to develop and manufacture—as much as $200 million for an individual biosimilar, according to an Amgen estimate.

“But back in 2015, 2016, there was not a lot of education,” Fish said. The FDA and CMS eventually began educating the public more broadly about biosimilars.

Oncologists Were Early Adopters

One thing that happened was that oncologists were among the first adopters, and to this day they are the most enthusiastic, as a group, about biosimilars, judging by their embrace of these agents. Fish said oncologists are well educated about biosimilars, have a favorable view of them, and have adopted them at a rapid pace.

“I’ve been going to the American Society of Clinical Oncology meetings for years. Five years ago, there must have been at least 3 or 4 different biosimilar lectures. And every year since then there have been lots of biosimilar lectures during those meetings,” she said.

By comparison, rheumatologists also are well educated about these agents, but are moderately favorable in their view of them, and uptake has been slow, Fish said. Gastroenterologists are at the tail end of the adoption curve, being moderately educated on biosimilars, possessing unfavorable views of them, and being slow about adopting them.

Another brake on the progress of biosimilars has been the web of contracts, rebates, and revenue streams between manufacturers and payers and clinical institutions, which in combination with a lack of payer management of prescription practices has stunted the development of this market, Fish said.

“So, you see a biosimilar on the market, but not a lot of utilization. You also could see it being put on formulary, but there are no step therapies,” she said.

Payers may be slow to adopt biosimilars, may cling to manufacturer rebates for originator products, or may jump into biosimilars and suffer the uncertainty of unclear financial benefits of doing so, she said. “That sort of middle, in-between area is that the payer will put a biosimilar on formulary but won’t take the reference product off.”

Payers may only dip a toe into the biosimilar pond by tweaking their policies just a little, such as by requiring a smaller co-pay for the biosimilar, which Fish described as “semimanagement.” More recently, the payer stance toward biosimilars has been characterized by aggressive management. “You see formularies that are going to get whittled down if there is more than 1 biosimilar product.”

But this form of management may assume an odd shape, she said, because payers may put a few biosimilars and their reference product on formulary, or just a brand and a biosimilar, or 2 biosimilars, she said.

A Look at Individual Trends

Fish reviewed some of the trends in individual biosimilar adoption. Infliximab biosimilars accounted for just 11% of market share in mid to late 2019, and even by the end of the second quarter of 2021, the originator product, Remicade, held a 75% share, she noted.

The story is better for short-acting filgrastim (Neupogen), she said. The biosimilar Zarxio had a 57% share of the market in the third quarter of 2019, vs 40% for Neupogen, and by the second quarter of this year, the originator held just a 26% share of the market.

Long-acting filgrastim (pegfilgrastim) biosimilars have taken an incrementally larger share of the market from Neulasta and its wearable injector version (Neulasta Onpro). Starting in the third quarter of 2019, the reference drug held just a 55% share of the market, and that declined to 52% by the second quarter of 2021, Fish said. Those are still large shares of the market for biosimilars.

“What really makes it interesting is that pegfilgrastim biosimilars are not just against Neulasta, but against Neulasta Onpro,” Fish said. “So, this is different than we were anticipating what the utilization of pegfilgrastim was going to be. We began looking at the utilization, and we saw a very big uptake against both the on-body applicator and the regular version of Neulasta.”

“Besides that, the manufacturer had tried to convert everybody to the on-body applicator and they were doing an amazing job of that,” she said.

A more traditional—or predictable—uptake curve has been seen in use of rituximab biosimilars. Fish noted that from 100% use of the originator brand, Rituxan, in the third quarter of 2019, biosimilars had assumed a 53% share of the market by the second half of 2021.

Rituximab is used in oncology and rheumatology, but it has been better received among oncologists, Fish said. However, the more recent market share numbers indicate that rheumatologists are picking up the biosimilar versions of rituximab.

The same pattern is seen for the bevacizumab market, which was dominated by the originator brand in the third quarter of 2019 (96%). By the second half of 2021, the reference brand share was 32%. Fish estimated cumulative bevacizumab biosimilar savings of $1.4 billion in the United States.

An almost identical biosimilar trajectory is notable in trastuzumab, where the reference brand went from a 96% share in the second half of 2019 to a 32% share by the middle of 2021, with cumulative savings of $2.5 billion, Fish said.

Epoetin alfa biosimilars have followed a relatively flat trajectory since mid-2019, according to Fish. Starting from a 41% market share, they now represent 44% of the market.

It’s important to note that the average sales prices (ASPs) for biosimilars and reference products have been decreasing over time, so the competition has stopped the upward march of reference product prices and resulted in savings for both reference products and biosimilars, Fish said.

The trastuzumab reference product (Herceptin) had seen a 15% ASP drop by mid-2021; Avastin (bevacizumab), 13%; Rituxan, 8%; Neulasta, 47%; Neupogen, 3%; Epogen/Procrit (epoetin alfa), 37%; and Remicade, 50%, according to Fish’s figures.