What's so scary about biosimilars?

Since the Hippocratic era, physicians have been charged to ‘do no harm’ to patients. As science advances, that task has become increasingly complicated: vastly improved methods of diagnosis and powerful new tools mean doctors have more and better information at their fingertips; while better medicine has made once devastating illnesses treatable.

At the same time, the tremendous pace of medical innovation forces new uncertainties upon doctors as new technology arises almost as soon as they become comfortable with the previous one.

When generic drugs first became available in the mid-1980s, many physicians scoffed at the notion that generics could be as safe and effective as originator drugs. But now, just 30 years later, 88% of all small-molecule drugs prescribed in the U.S. are generics.

A similar evolution happened in the 1990s, when physicians were initially skeptical of monoclonal antibodies like the first approved TNF-alpha inhibitor, Remicade (infliximab). But once the benefits for patients with inflammatory conditions became evident, physicians started to use such drugs widely. Now TNF inhibitors and other monoclonal antibodies are mainstay treatments for a variety of inflammatory conditions and cancers.

The common denominator for both of these shifts: education provided by various stakeholders, which ranged from drugmakers to patients, advocacy groups, trade associations, and the Food and Drug Administration.  

Next up: biosimilars

Biosimilar drugs are the next frontier for U.S. doctors. While biosimilars have been present in Europe for years, they have been slower to emerge in the U.S. with only two such drugs currently approved by the FDA.

Unlike generic versions of pharmaceuticals, biosimilars are deemed “highly similar” to their reference biologic drug rather than identical copies. Biologic drugs are generally derived from living organisms and typically are more complex in nature, meaning biosimilars by their nature vary slightly.  

In response to the need for education about biosimilars, companies like Sandoz (part of Novartis), Amgen and Samsung Bioepis are aggressively working to raise awareness and address physicians’ pressing concerns. Mainly, how approval for a biosimilar can be extrapolated across all of the uses a biologic is approved for, and whether biosimilars will prompt unwanted immunogenic responses.

Last March, almost a decade after the first biosimilar was approved in Europe, Sandoz’s Zarxio became the first to clear regulatory review in the U.S. Roughly a year later, Pfizer and Celltrion won FDA approval for Inflectra, a biosimilar version of Janssen’s Remicade.

But the pace of biosimilar development appears to be hastening. Earlier this month, two biosimilars received unanimous support from a key FDA advisory panel, sending a clear positive signal to the dozens of other biosimilars in development.

A growing biosimilar market in the U.S. bodes well for patients and payers. Cheaper versions of powerful biologics could boost patient access and lower payers’ cost burden.

Yet doctors still seems hesitant. More than half of doctors surveyed in May by SERMO, a global social network of physicians, said they would not be willing to prescribe a biosimilar drug. On the other hand, over 40% of doctors were open to learning more about biosimilars

Sandoz the pioneer

Sandoz has been one of the companies at the forefront of physician and patient education through extended print and digital marketing campaigns for Zarxio. To physicians, Sandoz emphasizes that Zarxio's approval in the E.U. in 2009 gives it more than 7.5 million exposure days outside of the U.S., and confirms its biosimilary to Amgen's Neupogen.

“Several recent surveys have demonstrated that there is still a need to educate physicians to ensure they understand licensed biosimilars are highly similar to their reference products in terms of efficacy safety and quality,” says Gregory Oakes, the vice president and head of biopharmaceuticals for North America at Sandoz.  

“As the company who brought the first biosimilar to the U.S. market, educating physicians is still very much a priority for us as part of our commitment to increasing patient access to quality biologics,” he adds.

Sandoz’s copy of Amgen’s anti-inflammatory blockbuster Enbrel was one of the two biosimilars to secure the support of the FDA’s advisory panel last week, setting up a potential approval later this year.

But development plans for a third biosimilar, referencing Amgen’s Neulasta, hit a snag in June when the FDA issued a complete response letter to Sandoz. Details of the initial rejection, first disclosed in Novartis’ quarterly earnings report, remain scant but it will likely set back Sandoz’s timeline.

A new competitor

As Big Pharma companies like Novartis and Amgen pile into biosimilar development, a new entrant could prove tough competition.

Samsung Bioepis, founded as a joint venture between Samsung and Biogen in 2012, is laser focused on biosimilar development. And to back up its R&D efforts, the Korean company has a science-heavy communications strategy aimed at healthcare providers.

The company’s 16-page, four-color stock brochure for physicians not only addresses the basic question of what a biosimilar is (and what it isn’t), but it also describes the reverse engineering required to develop biosimilars, as well as how advancements in analytical assay techniques have made the drug class possible.

Samsung Bioepis in June released switch data on three of its products—biosimilars of Enbrel, Remicade and Humira—highlighting data on patients who switched from originator drugs to one of the biosimilars. Samsung compared those patients who stayed on the original therapy, demonstrating similar efficacy and safety between the two groups.

Physicians are eager to see this type of data due to concerns over switching patients who are stable on a brand-name biologic. Worries usually hinge on whether a biosimilar will lead to harmful immunogenic reactions or render a patient unresponsive to treatment. Despite potential cost advantages, most physicians like to maintain a patient on therapy if it’s working. In other wordsif it’s not broken, don’t fix it.

Awareness to adoption

The early conversation around biosimilars centered on these concerns, but over the last several years, physicians have become more open to the development of biosimilars.

“Various surveys have shown that perception of biosimilars has significantly improved over the years,” said Klaus Falk, Vice President at Samsung Bioepis in a recent conversation with BioPharma Dive. Falk has tracked the changing attitudes, an unsurprising task for someone at a company dedicated on bringing biosimilars to market. 

“According to our conversations with various stakeholders, this may be largely attributed to physicians and other healthcare providers having greater familiarity with the science behind biosimilars, as well as the positive experiences they’ve had in prescribing and treating patients with these affordable, high-quality medicines,” he added. 

The role of patient advocacy groups

When it comes to educating patients, much of that is left to patient advocacy groups, such as the Crohn’s and Colitis Foundation of America (CCFA), which represents 1.6 million Americans with inflammatory bowel disease (IBD).

“Most patients don’t know exactly what a biosimilar is. They think it’s a generic. Not-for-profits like CCFA play an important role in educating patients and healthcare providers, especially nurse practitioners and physician assistants,” said Laura Wingate, vice president of Patient and Professional services at CCFA.

On June 1, the CCFA launched a biosimilars webinar for patients. Within six weeks, the program has already been viewed more than 2,300 times, suggesting strong interest from patients. In particular, the program focuses on patients who switch from an originator drug to a biosimilar.

“We want patients to be able to engage in a shared decision-making process with their doctors,” Wingate added.

Who benefits?

Although physicians are more knowledgeable about biosimilars than previously, their educational needs extend beyond clinical concerns. Biosimilars also promise to shake up the market for biologic drugs, with knock-on effects for pricing.

“When they are available, payers will be dictating what we as physicians do. It’s a race to the bottom,” said Dr. David Rubin, chair of the government and industry affairs subcommittee of CCFA’s National Scientific Advisory Committee. “Prices will drop as the biosimilars market expands and rebates and discounts come into play.” 

But will the patient be the ultimate beneficiary?  Rubin argues the effort to educate patients and physicians should not be solely focused on driving uptake.

“The conversation we’ve been having about biosimilars is superficial,” Rubin explained. “We believe that the net savings from biosimilars will go to the payers and not to patients, unless there is more transparency and advocacy in this area.”

“Without more transparency, we don’t believe the arrival of biosimilars will mean lower premiums and co-pays for patients. Nor do we believe it will increase access.”

Drugmakers like Sandoz and Samsung Bioepis are keen to tout the greater accessibility to powerful therapies which may have previously been limited by a biologic’s cost. But Rubin’s caution is worth noting—biosimilars aren’t an automatic win for patients unless the benefits of lower pricing leads to greater access.  

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