Dermatologists and some psoriasis patients might soon grapple with switching from a biologic to a biosimilar.
Dr. WuDermatologists and some psoriasis patients might soon grapple with switching from a biologic to a biosimilar. Infliximab-dyyb (Inflectra, Celltrion) a biosimilar to infliximab (Remicade/Janssen), which was FDA approved in 2016, is commercially available.
Others may soon follow. Infliximab-abda (Renflexis, Samsung Bioepis) was approved in late April this year. Etanercept-szzs (Erelzi, Sandoz), a biosimilar of etanercept (Enbrel, Amgen), was approved in August 2016, and adalimumab-atto (Amjevita, Amgen), a biosimilar of adalimumab (Humira, AbbVie), got the FDA’s nod September 2016. Erelzi and Amjevita are tied up in court with patent issues, according to Jashin J. Wu, M.D., who is a member of the National Psoriasis Foundation Medical Board, councilor for the International Psoriasis Council, and director of dermatology research for Kaiser Permanente Los Angeles Medical Center.
It’s not clear when Renflexis will be commercially available.
Dr. Wu, who presented on biosimilars in March 2017 at the annual MauiDerm meeting, says dermatologists are aware that biosimilars are on the horizon but many have questions and concerns about their use.
It’s true, he says, that much about biosimilar use remains a mystery for practicing dermatologists. Even Dr. Wu, who directs the Psoriasis Clinic at Kaiser Permanente Los Angeles Medical Center, isn’t sure when he’ll prescribe biosimilars or if he’ll have a choice in the matter.
Dr. Wu and colleagues surveyed 116 dermatologists about their familiarity of biosimilars in the treatment of psoriasis, results of which are published in the April Journal of Drugs in Dermatology. They found that on a scale of one to five, with one being very unfamiliar and five being very familiar, respondents reported a mean 2.7. However, respondents gave an average 3.4 rating to their concern (five being extremely concerned, in this case) about safety issues if patients are switched from the originator biologic to multiple other biosimilars.
“Our study was the first to provide insight into dermatologists’ current knowledge and perspectives of biosimilars. The majority were unfamiliar with biosimilars, skeptical regarding their efficacy and safety, and concerned regarding the practice of interchangeability,” Dr. Wu says. “We need to do a better job in educating our fellow dermatologists about biosimilars.”
Biosimilars are very similar to but are not exact copies of biologic reference products.
“So, these are not small molecules, where you can have an aspirin and a generic aspirin, which are basically the same. These are very complex large molecules, so you can’t have exactly the same product,” Dr. Wu says.
Biosimilars aren’t being manufactured by unreliable companies. In fact, many of the same pharmaceutical
Dr. Strobercompanies that make biologics also are making biosimilars, according to Bruce Strober, M.D., Ph.D., professor and chair of dermatology, University of Connecticut Health Center, in Farmington, who also presented on biosimilars at the MauiDerm 2017 meeting.
“The company that makes the biosimilar has a lot to lose by not making a good product. They are liable for problems that occur, whether they are related to differing efficacy or safety or immunogenicity,” Dr. Strober says. “In fact, companies that make biosimilars are very much in favor for very stringent requirements for approval of a biosimilar, because companies, like Amgen, Novartis, perhaps Pfizer, that are in the business of biosimilar manufacturing, think they can do it well and don’t want fly-by-night companies to be able to get in on the action and pull it off with a lower standard of medication.”
The approval process for biosimilars isn’t easy, according to Dr. Strober.
“The process is overseen by the FDA and; therefore, you’re looking at molecules that are manufactured and tested in every step of the developmental process in a very rigorous manner, such that, not only is the FDA assured of a good product but, more importantly, the company that makes it is assured of a good product that is neither better nor worse than the branded originator - the reference molecule,” Dr. Strober says.
Doctors’ concerns, unresolved issues
Dr. Wu says that dermatologists are concerned that if patients are stable on a branded biologic and they switch to a biosimilar, treatment could be less effective or cause more side effects.
“Safety is a concern,” Dr. Wu says. “Since clinical trials are much shorter with fewer numbers of patients, you may have rare events you might not pick up.”
The process for naming biosimilars could become a problem, according to Dr. Wu.
“The FDA has a guideline that they want a four-letter suffix after the generic name of a biosimilar, but the four letters have no meaning. I think that is a weakness of the proposal because if you have 10 biosimilars of Humira, there’s no way you’re going to be able to keep track of them,” he says. “But if they actually have meaning, reflecting the manufacturer’s name, that might help dermatologists to keep track of them.”
While the hope is that biosimilars will be a cost-effective option for patients, Drs. Wu and Strober are wondering how much cheaper they’ll be. In Europe, Dr. Wu says, biologics are up to 70% less expensive than branded biologics, but that’s because governments in European countries negotiate drug prices with manufacturers.
In the United States, where negotiations are often between pharmacy benefit managers and drug companies, the impact to the patient could be far less, but that remains to be seen, according to Dr. Strober.
“The Infliximab biosimilar, Inflectra, is said to be about 15% cheaper, compared to Remicade,” Dr. Wu says.
There are potentially troubling issues of pharmacy substitution and nonmedical switching.
“Say a patient is stable on a branded biologic, then is forced to switch to a biosimilar based on cost. That would be considered nonmedical switching. So, patients may have some side effects and loss of efficacy and increases in healthcare utilization,” Dr. Wu says.
Dr. Strober says that he thinks pharmacy substitution laws will vary from state to state.
“The question will become not if they have the ability to switch to a biosimilar, it’ll be to what extent is the prescribing practitioner notified of the switch,” Dr. Strober says. “In reality, a patient may be switched, unbeknownst to the provider, and whether that has clinical relevance is left to be seen.”
Most of the developed countries in the world have experience in using biosimilars, and that experience seems positive, according to Dr. Wu.
“In Norway, they’ve already used the Inflectra biosimilar. My colleagues there and in Denmark generally don’t have any problems. The patients seem to be doing fine and don’t have any side effects or loss of efficacy,” Dr. Wu says.
Dr. Strober says current studies on biosimilars suggest they are meeting objectives for efficacy, safety and immunogenicity, and they are stacking up to the reference biologics.
Dr. Wu says that despite some concerns, such as naming issues, he doesn’t think he and other dermatologists will have a choice when it comes to prescribing biosimilars to some psoriasis patients. Currently, 12 states have laws that state patients must be notified that a substitute or switch has been made. Some state laws require patient consent before the medications are switched.
“I think if the payor wants to switch over all the patients from the branded to the biosimilar, then the doctor will not have much of a choice. Depending on the state that they’re in, the doctor could put in brand medically necessary, so that would block the substitution. But I don’t think there is going to be a major concern if patients are switched over. I think it’s going to be OK, especially if these biosimilars are produced by reputable companies. Amgen, Sandoz, they’re the companies that are leading with a lot of biosimilars, and they’re very strong companies,” Dr. Wu says.
Dermatologists should brace for many more biosimilars in the future, while most are in rheumatoid conditions, there are biosimilars being developed for skin diseases, he said, including blistering disorders.
Still, a lot of the activity on biosimilars remains in the courtroom, according to Dr. Strober.
“My best bet is that 2017 will not likely be the year we have to wrestle with the issue of biosimilars,” he says.
Disclosures: Dr. Strober is a consultant and advisor to AbbVie, Amgen, Astra Zeneca, Celgene, Dermira, Janssen, Leo, Eli Lilly, Cutanea-Maruho, Medac, Novartis, Pfizer, Sun Pharma, Boehringer Ingelheim and UCB. He is an investigator for AbbVie, Amgen, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Eli Lilly, Janssen, Merck, Sun Pharma and Celgene. Dr. Strober is scientific director of the CORRONA Psoriasis Registry and receives grant support to the University of Connecticut for a fellowship program from AbbVie and Janssen.
Dr. Wu is an investigator for AbbVie, Amgen, Eli Lilly, Janssen, Novartis and Regeneron.