Patient engagement is key to building a biosimilar market

Print 10 May 2016
Mari Serebrov / BioWorld

There’s a whole lot of explaining to do before many U.S. patients and doctors will feel comfortable with biosimilars in place of their go-to biologics.

There also needs to be a lot of listening. The more biosimilar makers can understand patients and engage with them, the better, Seth Ginsberg, co-founder and president of the Global Healthy Living Foundation (GHLF), told BioWorld Today. He stressed that companies need to instill confidence in patients just like they do with investors. The same goes for regulators. They can’t just simply say, “Trust us.”

“If patients don’t have confidence in the biosimilar, it won’t work as well. Full stop. Period,” Ginsberg said.

For starters, the U.S. can learn from Europe’s uptake of biosimilars and its own experience in building confidence in generics, Pfenex Inc. CEO Bert Liang told BioWorld Today. When Hatch-Waxman was implemented in the 1980s to spur the development and use of generic drugs, the FDA launched a significant public outreach. “It will take no less of an effort” with biosimilars, Liang said.

Industry is already stepping up to the plate with some stakeholders. Biosimilar sponsors are spending a considerable amount of resources on education, and they’ve met with several provider organizations to address their concerns, said Liang, who also serves as chairman of the Biosimilars Council, a division of the Generic Pharmaceutical Association.

But industry’s efforts, especially when it comes to engaging with patients and doctors, are limited by FDA restrictions on how drug companies can interact with doctors and on social media. “The FDA is not the leader here,” Liang said. “They’re the laggard.”

Speaking from his own background as an oncologist, Liang recommended that the education effort for doctors start with specialty groups that frequently use biologics and then spread to other doctors. Social media would be the best platform for reaching patients, as it offers a broad platform. But to put out credible, unbiased information about biosimilars online, companies have to navigate a meandering regulatory highway as they try to discern what the FDA will consider “reasonable discourse,” Liang said.

SILENCE ON EXTRAPOLATION

The agency has posted a few informational materials about biosimilars on its website, including a 1.5 credit continuing education course for health care professionals. The course and the materials briefly define biosimilars and the approval process, but it’s what they don’t mention that’s worrisome to many doctors and patients – extrapolation. None of the materials mentions the word or explains the concept or science behind it.

Rather than having biosimilars repeat the safety and efficacy trials of the reference product for every indication, the FDA requires them to demonstrate similarity in one or a few indications. Those comparative studies are not the same as safety and efficacy trials and may use different endpoints and study populations. After reviewing the data, the FDA may extrapolate biosimilar approval for all the indications demonstrated by the innovator.

Extrapolation of indications is the key concept behind the abbreviated biologics pathway, but it isn’t a given. Steven Kozlowski, director of the FDA’s Office of Biotechnology Products, pointed out at an advisory committee meeting on Celltrion Inc.’s biosimilar to Remicade (infliximab, Janssen Biotech Inc.) that if a sponsor needed clinical data for every indication, the biosimilar path would be much more cumbersome than starting fresh with a new biologic. In developing a biosimilar, the sponsor is filling in and confirming the data – not reproving it, he said. (See BioWorld Today, Feb. 10, 2016.)

The problem is that the agency has released no guidance on when or how data will be extrapolated. Doctors, patients and some biologics makers have requested that labeling show which indications are extrapolated. The FDA brushed those concerns aside when it issued draft guidance on biosimilar labeling. The guidance recommended that biosimilar labeling reference data from the safety/efficacy trials conducted by the innovator rather than the biosimilar’s own comparative data. (See BioWorld Today, April 1, 2016.)

“We think that including comparative clinical data in biosimilar product labeling would be confusing or even potentially misleading to health care providers,” said Leah Christl, associate director for therapeutic biologics and lead of the biosimilars staff at the FDA’s drug center. “Ultimately, the comparative data are useful for the FDA to make a decision about biosimilarity, but are not likely to be relevant to a health care provider’s prescribing considerations.”

The FDA’s response may be an attempt to not prejudice a fledgling market against biosimilars, Siegmund Gutman, chairman of Proskauer Rose LLP’s life sciences patent practice, told BioWorld Today. On the other hand, by not discussing the issue in the labeling guidance, the agency missed an opportunity to create more certainty about the type of data needed for extrapolation.

Some patient groups, like the GHLF, aren’t totally against extrapolation, but they want it done responsibly. Extrapolation should only be done with best-in-class biologics, not every biologic, Ginsberg said. “Don’t we want to do better for patients? For science? For medicine?” he asked.

PHARMACOVIGILANCE AND OTHER WORRIES

There are other issues biosimilar education campaigns will need to address. And some of them could be used by biosimilar sponsors to differentiate their products in what could become a crowded field.

One concern with extrapolation is that a biologic’s mechanism of action may not be the same in every indication. Because of that, postmarket pharmacovigilance is crucial, Ginsberg said. Several patient groups and doctors raised that point in February when the FDA convened the Celltrion advisory committee.

While biosimilar sponsors in the U.S. have to file adverse event reports like any other drug company, they don’t have to do the extensive postmarket testing and observational studies that many of the reference biologics must undergo. Other countries have more stringent postmarket regulations.

In Japan, for instance, a sponsor must submit biweekly reporting for every patient taking the biosimilar for the first six months following approval. Australia subjects biosimilars to the same post-registration and pharmacovigilance requirements as the reference product. And India requires periodic safety update reports every six months for the first two years following approval of a biosimilar and then once a year for the next two years. Biosimilar sponsors in India also have to conduct at least one postmarket safety and immunogenicity trial.

Other patient concerns that industry, the FDA and policymakers must address if they hope to build a robust biosimilar market in the U.S. include:

• Manufacturing quality and consistency. Given the complexity and sensitivity of biologics, patients want to be assured that biosimilar makers entering the market have the capability to produce a consistent, quality product over the long term to avoid the shortages that have been experienced in the generics market. “Biosimilars need to raise the bar, not lower the bar,” Ginsberg said.

• Continuity of support services. Phone hotlines, access to nurses, online information, co-pay cards and other services typically offered by innovators can make the difference in whether a biologic protocol works for an individual patient, Ginsberg said. The fear is that biosimilar sponsors without previous biologics experience will not understand the importance of such services and may not offer them.

• Cost savings for patients. While biosimilars are expected to offer some savings, there’s no certainty payers will pass it on to patients. “If it’s not reaching the patient’s wallet, it’s irrelevant,” Ginsberg said. Any policy that doesn’t pass the savings to the patient will be “counterproductive and borderline insulting,” he added, especially since patients are the ones taking the drugs and participating in biosimilar clinical trials.

“We want this to happen. We want biosimilars,” Ginsberg said. But patients shouldn’t have to sacrifice safety, quality or services to develop a biosimilars market.

Liang said, “This really is about patient access.” In his experience in treating patients, he found that one of the biggest worries was patients not being able to buy the drug they needed. If patients don’t take a drug because they can’t afford it, their condition is likely to worsen and the cost of their care increases.

BioWorld Today will conclude its look at biosimilars in the U.S. Tuesday with thoughts on what lies ahead for the new market.

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