Is the Biosimilars Waiting Game Finally Over?

The passage of the Biologics Price Competition and Innovation Act (BPCIA) a decade ago was supposed to usher in a new era: High-priced biologic drugs would have competitors, called biosimilars, that were just as safe and effective. This price competition would then drive down healthcare costs.

That was the theory anyway.

In actuality, just as the broader ACA continues to be tied up in court battles, the biosimilars market has been hobbled by legal wrangling. Although the BPCIA was just one provision of the ACA, biosimilars were seen as one of the surest market-oriented ways to reduce healthcare costs.

Optimists see hope in the growing number of FDA-approved biosimilars. Their less-sunny counterparts, however, see unfulfilled potential and a gap between the number of approved biosimilars and the number on the market.

The ‘similar’ in biosimilar

Biologics — agents derived from living organisms rather than chemicals — date back to the beginning of the 20th century. But recombinant DNA technology developed in the 1970s and 1980s launched a new era: synthesized biologics
instead of animal-derived agents. The price tags on some of the biologics were in the tens of thousands of dollars, which, at the time, seemed expensive.

The BPCIA created an accelerated pathway for drugmakers to gain approval for products that were substantially similar to existing biologics. Unlike small-molecule generics, biosimilars are not exact copies of their reference products. A small-molecule drug may comprise a couple dozen atoms; a biologic, hundreds or thousands. The chemical processes used to make small-molecule drugs ensure an exact copy (although the inactive ingredients to make the pill that contains the drug may differ). The fact that biologics are derived from living organisms also adds some slight — but not necessarily meaningful — variability.

Christine Simmon, executive director of the Biosimilars Council, a group that lobbies for the industry, says that although biosimilars are costly to produce, they offer enormous potential to lower prescription drug costs. “(Biosimilars) represent a tremendous savings opportunity for patients and taxpayers,” she says. “We are seeing ... up to 30% discounts now with biosimilars that are on the market.”

The FDA has approved 28 biosimilars so far. The first, approved in 2015, was Sandoz’s Zarxio (filgrastim-sndz), a biosimilar of Amgen’s cancer drug Neupogen (filgrastim). Zarxio came on the market just six months after approval, but most other biosimilars have not had such a quick journey. Seventeen of the 28 approved biosimilars were on the market at the beginning of July, so the gap is narrowingbut still there.

The approved, on-the-market biosimilars include a handful of Genentech’s chemotherapy drug Herceptin (trastuzumab), as well as biosimilars of Amgen’s bone-marrow stimulant Neulasta (pegfilgrastim) and Janssen Biotech’s immunosuppressant Remicade (infliximab). Six biosimilars for AbbVie’s Humira (adalimumab) have also been approved, dating back to September 2016, but none have yet made it to market.

Perilous patents

Simmon says the Humira biosimilars and others aren’t on the market because of litigation brought by the makers of the reference products on which the biosimilars are based. As the costly lawsuits drag out, they extend market exclusivity for the higher-cost brand-name products. Critics, however, charge that the lawsuits are based less on valid legal objections and more on a fear of competition.

Simmon says one way that brand-name drugmakers seek to protect market exclusivity is by filing and defending copious patents. “It’s very common for a brand-name biologic manufacturer to obtain as many patents as possible,” she says, noting that the patents often cover things far beyond the underlying biologic, even extending to language on product labels.

In the case of Humira, AbbVie’s legal strategy prompted a grocer’s union to file a class-action lawsuit arguing that the biopharmaceutical company is unfairly using a “legal thicket” to prolong its monopoly. AbbVie, however, has reached settlement agreements with all of its potential competitors to preserve Humira’s market exclusivity until at least 2023.

In resolving the final such lawsuit last year, AbbVie’s chief legal officer, Laura J. Schumacher, said the company’s patents fund innovation. “As an innovation-driven biopharmaceutical company, we will continue to develop novel cures for the toughest health challenges and rely on a robust patent system to protect that investment in innovation,” she said in a press release.

Market challenges

Reference product manufacturers have also sought to limit the impact of biosimilars once they eventually reach the market, according to Ameet Sarpatwari, J.D., Ph.D., an assistant professor at Harvard Medical School. “One strategy originator manufacturers have employed to limit biosimilar uptake has been to negotiate formulary exclusivity with payers,” wrote Sarpatwari and his co-authors in an article about biosimilars not living up to their promise published in the August 2019 American Medical Association Journal of Ethics.

Such deals often include rebates for payers or PBMs that essentially create an incentive structure that keeps higher-priced products on the market. That, in turn, has the effect of reinforcing physician comfort with the brand-name drugs, wrote Sarpatwari.

Insurers and PBMs have questions about how the biosimilars market will eventually shape up, Simmon says. A physician can prescribe the generic of a small-molecule drug and know that no matter who the manufacturer is, the generic will almost certainly be available at the pharmacy and will work the same way as the reference product. Will the same be true of biosimilars? “Plans and PBMs, generally speaking, have questions about whether or not there will be a lot of interchangeable biosimilars in the future, as well as ... how much growth we can expect in the availability of biosimilars,” she says.

Pushing for change

For Simmon, one priority is avoiding lengthy court battles. She wants to preserve the opportunity for drug companies to enter into patent settlement agreements, which offer a way to quickly legal disputes. She also wants to see patent disputes go through the inter partes review process before the Patent and Trademark Board, an adjudicative body within the U.S. Patent and Trademark Office, rather than get ensnarled in protracted court cases.

Also on Simmon’s wish list is patent reform that puts limits on what can be patented. Finally, she says, the FDA needs to find a better way for interested parties to locate relevant patents — without having to hire costly law firms. “Right now that’s very time-consuming and expensive,” she says, “because there is no resource you can just search through and find patents.”

Additionally, America’s Health Insurance Plans (AHIP) is asking lawmakers to reduce the patent life for biologics from 12 years to seven, arguing that doing so would facilitate earlier availability of biosimilars and further open up the market. Drugmakers are opposed, saying they need a long period of exclusivity to earn back their investment and that it serves the larger purpose of encouraging biotech innovation.

Although it’s clear that biosimilars are here to stay — hundreds remain in development — such regulatory changes could be the deciding factors in when biosimilars finally achieve acceptance and realize their potential in this, their second decade.

Jared Kaltwasser is a healthcare reporter based in Iowa.