Grab a big bowl of popcorn and nestle into a comfy seat, for the biologic–biosimilar debate in the autoimmune sector isn’t expected to reach a resolution anytime soon. From patent litigation to pricing wars and questions about interchangeability, this flick looks to register high on the action detector.

Biologics are the fastest-growing drug segment — and, within the autoimmune sector, the priciest. Many methods to preserve market share exist, but biologics can only hold back biosimilars for so long.

With the average prescription ringing in at $3,587.83, specialty drugs to treat inflam­matory conditions took top bill­ing among expensive drug classes, according to an Express Scripts report. The top five drugs in the class include Abb­Vie’s Humira Pen, Amgen’s Enbrel, and Humira, all for the treatment of rheumatoid arthritis; Celgene’s Otezla (apremilast) for plaque psoriasis; and Janssen Biotech’s Stelara (ustekinumab) for plaque psoriasis, psoriatic arthritis, and Crohn’s disease. Humira (adalimumab) and Enbrel (etanercept) alone took 70% of the market share in 2016.

See also: Top 25 autoimmune brands in 2016, based on U.S. sales

Biosimilars wave promises of more treatment options at a potentially lower price. The trouble is that prescribers and payers have differing ideas about their utility in treating patients with rheumatoid arthritis, psoriasis, and other conditions.

Rheumatologists hold a wide range of opinions about biosimilars, says Nathan Wei, MD, director of the Arthritis Treatment Center in Frederick, Maryland. “Some actively welcome biosimilars and think they’ll be the panacea for drug costs. But those adamantly opposed worry they won’t have the beneficial effects of brand-name drugs,” Wei says.

By targeting the underlying cause of disease, biologics pose a huge breakthrough for patients with autoimmune diseases. There’s no doubt brand loyalty runs deep. “Consumers are involved in this space and know their products,” says Mark Ginestro, principal at KPMG Strategy. “That is sure to slow down product switching.”

See also: MedImmune goes after challenging lupus market

Three of the four FDA-approved biosimilars fall in the autoimmune category: Sandoz’s Erelzi, biosimilar to Enbrel; Pfizer’s Inflectra, biosimilar to Janssen Biotech’s Remicade (infliximab); and Amgen’s Amjevita, biosimilar to Humira. The fourth is Zarxio, biosimilar to Amgen’s oncology drug Neupogen.

With draft guidance released last winter, the FDA is calling on biosimilar developers to produce switching-study data to establish interchangeability with reference products. “It could potentially speed adoption, but also cost manufacturers in both time and money,” explains Trinity Partners principal Jillian Godfrey Scaife.


Although approved in the U.S., the Humira and Enbrel biosimilars have been held up by patent disputes. To complicate matters, the already-approved biosimilars do not have interchangeability status, as their approvals predated the requirement. Some believe the FDA issued hasty approvals before ironing out concerns related to patient safety, including interchangeability status and indication extrapolation.

“Companies are generally happy there is guidance now, but it definitely makes the investment hurdle higher,” Ginestro says.

But for smaller players in the space, the guidance could quash the chance of reaching market. Other forc­es could also alter the trajectory. “The BPCIA [Biologics Price Competition and Innovation Act] would have been in jeopardy if President Trump and Congress had scrapped the ACA,” notes David Rosen, a partner at Foley & Lardner. And with a new FDA commissioner pending, many wonder if review and approval models will be revamped.

See also: The FDA approves Amgen’s biosimilar version of Humira

The U.S. biosimilar market could take a few cues from abroad. In Norway, for instance, the government funded an interchangeability study for a Remicade biosimilar. Proving interchangeability had a profound effect on its healthcare system.

Major health insurers ponying up as study sponsors would prove a viable parallel. “The negotiating power that payers have may be the difference in setting affordable prices for biosimilars,” explains Stephan Gauldie, SVP of strategy consulting at Back Bay Life Science Advisors.

The U.S. is taking notes on the reception of biosimilars in other markets, including the extent to which marketing investments have an impact, Ginestro notes. “Because autoimmune drugs are chronic medications requiring patients to take them for the long haul, patient and physician engagement is more influential than in other therapeutic categories,” he explains.

Brand manufacturers are willing to do whatever it takes to protect market share and fend off biosimilar competition. Despite their having a few power plays, their branded biologics don’t face an easy road.


In late April, the FDA rejected Eli Lilly and Incyte’s experimental RA drug, baricitinib, asking the manufacturers to provide more data.

Some autoimmune leaders are getting mighty creative as a result. In a major defensive move aimed at Enbrel’s biosimilar competition, Amgen negotiated an outcomes-based contract with insurer Harvard Pilgrim that aims to tie the ultimate cost of Enbrel to its real-world clinical efficacy and could set a precedent.

Meanwhile, AbbVie is doing everything possible to maintain Humira’s place. It filed a patent infringement suit against Amgen to block the launch of its biosimilar last August. An Abb­Vie spokesperson declined to comment on specific litigation related to Humira, but said the company continues to invest in new indications and enhancements for patients with unmet medical need.

See also: Three kinds of drugs, like those that treat RA and diabetes, drive increase in spending

Similarly, Amgen slapped Novartis’ Sandoz with a patent infringement suit regarding Enbrel, a case that was slated for oral arguments in the Supreme Court on April 26. “Biosimilars are taking longer to reach market than anyone expected,” Ginestro says. “It’s apparent now that patent challenges are voluminous and complex.”

Oncobiologics plans a 2020 launch of its Phase III biosimilar of Humira, but CEO Pankaj Mohan is well aware that the IP landscape could push that date back to 2025. “Barriers need to be addressed if biosimilars are going to be introduced in a timely manner,” he says.

Whether big pharma is deliberately trying to keep less expensive treatments off the market or simply recoup its investments depends upon whom you ask. “The originator companies will do everything they can to delay biosimilar launches, but it’s a sociopolitical need to have less expensive products available,” Mohan says.

Opinions on potential biosimilar savings are scattered and confusing. Some reports mention saving the healthcare system $250 billion over the next 10 years, but the Congressional Budget Office chimed in with a far more conservative estimate of $25 billion.


Current biosimilar discounts fall in the 15% to 25% range. But, according to Mohan, that doesn’t account for the significant discounts expected by end users and payers. Instead, he predicts eventual discounts of up to 50%, especially in the autoimmune category.

But Rohit Sood, consulting managing director at inVentiv Health, says price points for biosimilars won’t decrease by more than 30%. The pricing needle is unlikely to move until competition heats up with the arrival of more biosimilars.

“The savings potential of biosimilars is highly confusing at the moment,” Wei points out. “Payers will make sure biosimilars are tier one in the formularies, if they can.”

See also: With competition lurking, Eli Lilly’s baricitinib must show unparalled efficacy

Some experts think if biosimilars start moving to market more quickly, then brand manufacturers will respond with lower product prices. Gauldie doesn’t see a way for biologics to compete on price. Drawing a parallel to the generics market, he says, “Biologics would emphasize the brand and biosimilars would emphasize price, assuming interchangeability is sorted out first.”


To successfully position biosimilars, manufacturers must educate HCPs about how bio­similars can achieve the same outcomes as existing products. According to Sood, it will be critical to think beyond assets to entertain core offerings such as patient and physician services, quality manufacturing,medical education, promotional communications, and engagement with policymakers.

As with any launch, however, a biosimilar manufacturer’s success will depend on its ability to execute strategy and establish positive customer product perceptions. “Biosimilar success will hinge on the stakeholders’ comfort level in accepting and adopting products,” Trinity’s Godfrey Scaife says. Taking a different approach from branded products, campaigns will need to define biosimilars and explain how they stack up against biologics.

See also: Fueled by precision medicine, drugmakers delve deeper in autoimmune diseases

Additionally, patients need to have their questions regarding biosimilars — related to efficacy, safety, and side-effect profiles — addressed with clear communications programs. “They feel they have the most to lose,” says Rafal Kokolus, senior engagement manager, inVentiv Health Consulting.

But brand manufacturers will invest more heavily in value-added services. “Some TNFs have nurse ambassadors on call 24 hours a day, providing support and hand-holding during injections,” Wei says. “It’s unlikely biosimilars will be able to offer support services as the branded drugs do.”