The implications in the future of biosimilars

While biosimilar medications for the treatment of psoriasis have yet to gain approval by the U.S. Food and Drug Administration (FDA), these medications have been approved for use in Canada and the European Union. And the FDA is evaluating biosimilar versions of infliximab, etanercept, and adalimumab, according to Andrew Blauvelt, M.D., M.B.A., president and investigator, Oregon Medical Research Center, Portland.

Biosimilar versions of etanercept and adalimumab could be available in the United States within the next three years. And when they do become available, biosimilars are likely to become part of the daily prescribing practices of U.S. dermatologists, according to Bruce Strober, M.D., Ph.D., professor and chair of dermatology at the University of Connecticut School of Medicine.

“Many unknowns exist right now, however, especially in terms of the pricing, regulations and long-term quality of these new drugs,” Dr. Blauvelt says.

Lower cost; more access?

A big benefit of biosimilars is their potential lower cost, compared with biologics.

“Cost is predicted to be lower than the original biologic products, and this may increase access and increase use of these drugs,” Dr. Blauvelt says. “Although it is unknown what the exact prices will be in the U.S., estimates range anywhere from 30% to 70% of the costs of the original biologic product.”

Accessibility and market penetration of the biosimilars will depend a lot on how branded biologic manufacturers adjust their pricing with major insurance carriers to be competitive, according to Dr. Strober.

“Regardless, it is logical to assume that the arrival and market penetration of biosimilar drugs will create some downward pressure on prices for all biologic drugs. Whether this increases access to these drugs is left to be seen,” Dr. Strober says.

NEXT: Questions around interchangeability

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About interchangeability

One of the stumbling blocks to truly determining interchangeability is the FDA has not defined exactly what makes a biosimilar interchangeable, according to Jashin J. Wu, M.D., director of dermatology research, Kaiser Permanente Los Angeles Medical Center, in Los Angeles.

“They may be highly similar to the originator, and they may be interchangeable but the FDA has not given any guidelines as to exactly what that means,” Dr. Wu says.

Most of the testing for biosimilar products as well as comparisons to original biologic products occur in the laboratory; not in the clinic, Dr. Blauvelt says.

“Extensive laboratory comparisons are made, but only minimal clinical study comparisons are required prior to drug approval. The hope is that the decreased clinical study programs for biosimilars will lead to much less overall costs in clinically developing these drugs and getting them on the market,” Dr. Blauvelt says.

“Given that, most biosimilar products will be approved with relatively limited clinical study data behind them. This may be OK for the short-term, where the drugs tested so far appear to be similar to original biologic products over a six- to 12-month period, but long-term clinical data on biosimilars are lacking. These products will likely be on the market with no knowledge of long-term efficacy, safety and immunogenicity data,” he adds.

Dr. Strober does not believe biosimilars will pose an increased risk to patients because the current crop of biosimilars working through the developmental pipeline and approval process are “professionally” created, manufactured and tested.

“The developmental process for biosimilars, while very different from that of the reference products, is quite rigorous and being conducted by very well-known companies that are highly experienced in the manufacture and clinical testing of biologic drugs. For example, two of the biosimilar-manufacturing companies, Amgen and Novartis, actually currently make FDA-approved branded biologic drugs for moderate-to-severe psoriasis,” Dr. Strober says.

The question that remains, according to Dr. Strober: Will all biosimilars that dermatologists are ultimately required to use in dermatologic conditions actually be tested in those conditions as part of their approval pathways, or will the FDA accept clinical trials in non-dermatologic conditions with extrapolation to dermatologic approval?

“The lack of testing in dermatologic conditions would leave some doubt regarding the relative efficacy and safety of the biosimilars vis-à-vis the reference product in the dermatologic condition,” Dr. Strober says.

Tricky laws, requirements

Navigating legislation around biosimilar use might prove challenging for dermatologists, Dr. Wu says.

Having patient access to biosimilars could mean extra paperwork for dermatology practices. Part of the reason is that states have different laws regarding use of biosimilars, including substitution, which may result in nonmedical switching, where patients are automatically switched to biosimilars because of insurance reasons or copay issues; not because of doctors’ orders.

“Pharmacists [also] may do automatic substitutions for the biosimilars, so then doctors’ offices may have to fill out extra paperwork to prevent that,” Dr. Wu says. “Patients may be affected if they’re stable on a branded biologic and then are switched over to a biosimilar. They may have lost efficacy with the biosimilar or they may have increased side effects. There are a couple of studies from Europe that have shown that these patients, after nonmedical switching, had increases in side effects, loss in efficacy and increased health care utilization, meaning longer inpatient visits, more ER visits and more outpatient visits.”^1,2

Another issue that could muddy the biosimilar waters has to do with nomenclature. As of now, the FDA has a guidance proposal that the agency wants to make a four-letter suffix after each biosimilar’s International Nonproprietary Name, or INN. As they stand, the four-letter suffixes have no meaning, according to Dr. Wu.

“It’s going to be very confusing when you have the originator and then have five to 10 adalimumab biosimilars that all have four-letter suffixes that are gibberish. It seems to me that if they are going to have a four-letter suffix, they should at least have it stand for the company’s name,” Dr. Wu says.

NEXT: More unknowns

More unknowns

Regulatory issues regarding biosimilars are numerous and complex, according to Dr. Blauvelt.

“If and when they are approved by the FDA, it is unknown how insurance plans will pay for these drugs; whether biosimilars will be required to be used prior to original products (due to cost); and whether pharmacists will be able to substitute (with dermatologist consent or not) a biosimilar product for a corresponding original biologic product,” Dr. Blauvelt says.

Biosimilars are likely to play an increasing role in dermatology practices during the next decade. Just how big a role depends on the ability of the biosimilar manufacturers to convince payers that a specific biosimilar saves the payer money, as well as convince patients and practitioners that there are no compromises on safety or efficacy with these molecules when used in clinical practice, Dr. Strober says.

Interestingly, even if the FDA gives the thumbs up for biosimilars, turf issues could further delay their marketplace availability, according to Dr. Wu. Specifically, patent issues, including those for Humira, Enbrel, Remicade, etc., may be set to expire soon but lawyers could try to extend the patents and the biosimilar companies may try to invalidate the patents.

“In the end, practitioners and patients who wish to choose a specific mechanism of action for the treatment of a dermatologic condition might have no choice regarding which drug they can actually prescribe. Instead, the payer will dictate the choice, reference product or biosimilar, based on cost,” Dr. Strober says.

Disclosures:

Dr. Blauvelt reports relationships with Novartis, Dermira, Genentech, Regeneron, Abbott, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Galderma, Janssen, Merck, Pfizer, Regeneron and Sandoz.

Dr. Strober reports that he receives grants for research and clinical trial support from AbbVie and Janssen. He’s on the speaker’s bureau for AbbVie and is a consultant or on the advisory board for AbbVie, Amgen, Celgene, Dermira, Janssen, Leo, Eli Lilly, Maruho, Medac, Novartis, Pfizer, UCB. Dr. Strober is an investigator for AbbVie, Amgen, Boehringer-Ingelheim, Glaxo Smith-Kline, Novartis, Eli Lilly, Janssen, and Merck. And he is a scientific director for the Corrona-NPF Psoriasis Registry.

Dr. Wu reports that he received research funding from AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Coherus Biosciences, Dermira, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Regeneron, Sandoz, and Sun Pharmaceutical Industries; he is a consultant for AbbVie, Amgen, Celgene, Dermira, Eli Lilly, Pfizer, Regeneron, and Sun Pharmaceutical Industries.

References:

1.     Wolf D, et al. 10th Congress of European Crohn’s and Colitis Organisation, 18–21 February 2015, Barcelona, Spain. p504.

2.     Rubin DT, et al. 10th Congress of European Crohn’s and Colitis Organisation, 18–21 February 2015, Barcelona, Spain. p354