Look out, AbbVie. Thanks to Boehringer, your Humira biosimilar defense isn't over yet

Could Boehringer Ingelheim and its biosimilar turn out to be AbbVie's Humira stumbling block? So far, the German drugmaker has refused to back off its patent challenge, putting up a scrappy defense in court rather than settling with AbbVie as its rivals have.

AbbVie argues that Boehringer’s biosim, which won U.S. approval last year as Cyltezo, steps on dozens of its Humira patents. Boehringer claims AbbVie is using a “patent thicket” of overlapping and add-on patents—plus the litigation process itself—as a defense mechanism for its blockbuster.

Zachary Silbersher, a patent attorney with Markman Advisors, said the issue of a biologics “patent thicket” hasn’t played out in a courtroom before. That, plus the fact that billions of dollars are at stake, make the Boehringer and AbbVie fight a closely watched case for experts in pharma. It'll be a tough win for Boehringer, he figures; AbbVie has denied the allegations.

The Boehringer defense is playing out as the FDA and other biosim makers are working to promote the copycat drugs in the U.S., where uptake hasn't been nearly as strong as in Europe. There, biosims have caught on quickly, saving money for health systems while taking a big bite out of branded sales. In the U.S., just four biosims have launched, and they've produced savings far lower than initial estimates. Twelve biosims have won U.S. approval, but many must still wait out or sort out patent challenges. Overall, uptake for early biosims has been so slow that Pfizer filed an antitrust suit against J&J for its contracting strategies to defend Remicade. 

And on the savings side, Humira is a big opportunity. The megablockbuster continues to rake in record-breaking sales; it was the biggest-selling drug on the globe in 2017, collecting more than $18 billion worldwide. Meanwhile, Amgen, Mylan and Samsung Bioepis have agreed to hold off on launching their versions of the autoimmune drug until 2023, pushing off competition in the U.S. even as biosims are set to hit in Europe next month. 

To win, Boehringer will have to prove that it doesn't infringe AbbVie patents or that they're invalid, Silbersher said. But Boehringer's strategy is different. It's pursuing a defense of "unclean hands," arguing that AbbVie acted inequitably in pursuing so many patents and that the case should be thrown out altogether. Silbersher said he believes the strategy is a "Hail Mary."

RELATED: AbbVie files another Humira patent suit, this time against Boehringer Ingelheim

Litigation over 70-plus patents will likely take years to play out, Silbersher said. Including appeals, it could be 2023 before Boehringer could launch its biosim even if it wins. Silbersher speculated that many biosim developers anticipated those challenges and chose to settle instead of fighting. AbbVie sued Novartis' Sandoz unit over its biosim hopeful just recently, so it's not yet clear whether that company will resist settling, too.

“On its face, it’s not clear that AbbVie did anything wrong,” Silbersher said. “If we assume that all of these patents are legitimate and that [AbbVie] didn’t lie to the patent office, then the fact that the patent office gave it 100 patents isn’t AbbVie’s fault.” 

A courtroom “might not be the right place” to resolve the patent thicket issue, Silbersher said. Even if it’s “bad policy” and the conduct is legal, a judge won’t be able to intervene, he pointed out. Still, it’s unclear which authority could or would take up the issue; one possibility would be an “informal directive” at the PTO making it harder to secure patents for biologics, he said.

U.S. District Judge Richard Lloret recently ordered AbbVie and Boehringer to produce certain documents and records for discovery, and to provide a status report on the case by Sept. 15.

RELATED: FDA chief Gottlieb blames drugmakers for ‘anemic’ biosimilar market 

The legal battle comes as the FDA, biosimilars makers and affordable drugs advocates push to speed up approval and adoption. The agency held a daylong hearing last week to gather input, with representatives from Johnson & Johnson, Amgen, Pfizer, Mylan, PhRMA and more participating. 

This summer, FDA Commissioner Scott Gottlieb, M.D., blasted patent litigation and payer contracts for their role in the “anemic” U.S. biosim market. Speaking at an event at the Brookings Institute, he said drugmakers should be able to defend their drugs, but “rebating schemes or patent thickets that are purely designed to deter the entry of approved biosimilars are spoiling” competition. 

“Long-dated contracts are another toxin,” he added. “The branded drug makers thwart competition by dangling big rebates to lock up payers in multiyear contracts right on the eve of biosimilar entry.” At the recent FDA hearing, Gottlieb said he’s “not satisfied with the current state of the biologics market and biosimilars in particular,” as quoted by the Center for Biosimilars.

RELATED: AbbVie's Humira gets biosim reprieve—and Amgen wins copycat advantage—in patent deal with Samsung Bioepis 

Pfizer’s Inflectra—a biosim to J&J’s Remicade—is an object lesson in challenges that biosimilar makers face.

Pfizer sued J&J last year for “anticompetitive” contracting that it says is blocking its market access. The company alleges that J&J tied discounts on Remicade’s massive patient base to the stipulation that payers don’t use biosims, and that the situation won’t change unless a court intervenes. J&J moved to dismiss the lawsuit by arguing that Pfizer’s claims weren’t substantial enough for argument, but a judge ruled that the lawsuit may proceed.

In a recent white paper by Matrix Global Advisors—sponsored by Boehringer Ingelheim—authors said the U.S. biosims market needs assistance on multiple fronts. To boost uptake, biosim pricing needs to be competitive, while doctors and patients need more education about the alternatives. Employer-sponsored health plans should urge PBMs to encourage biosim uptake, and payers should ensure that their contracting doesn’t dissuade use of biosims, the authors wrote. 

Lastly, the group said the FDA “must continue to pursue an open, transparent, and responsive regulatory review process.”