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Study Bodes Well For Biosimilars But Highlights Need For More Research

Medical vials and Syringe, Isolated on Blue background

Research released Monday finds comparable safety and efficacy for one type of biosimilar drugs, complex medicines intended to be near-copies of some of the most costly prescription drugs on the market, but highlights the need for more information on the products.

In the absence of generic alternatives to these pricey treatments, called biologics, biosimilar drugs hold great promise for U.S. patients and their wallets.

Biologics are drugs made or derived from living cells using cutting-edge biotechnology. But, because their molecules are more complex than those that make up typical drugs, exact-copy generics aren鈥檛 possible. Instead, a new class of drugs called biosimilars have the potential to be generic-like substitutes needed to keep costs down.

Researchers at Johns Hopkins University and Brigham and Women’s Hospital evaluated a series of studies regarding a very specific group of biosimilars — those that treat inflammation for patients with rheumatoid arthritis and inflammatory bowel disease, called TNF-alpha inhibitors. They systematically reviewed 19 studies to determine how these biosimilars compared with the brand-name drugs, focusing on safety and efficacy. They concluded the biosimilars are 鈥渋nterchangeable鈥 with the original versions, such as Remicade and Humira. Their and an accompanying were published in the Annals of Internal Medicine.

“We examined one very costly and commonly used class of biologic therapy,鈥 said study author Dr. Caleb Alexander, codirector of the Johns Hopkins Center for Drug Safety and Effectiveness. 鈥淭he totality of evidence strongly supports the comparability of the biosimilar and branded product.鈥

Although the analysis was reassuring, experts didn鈥檛 find the results surprising.

鈥淗onestly the data have been pretty consistent,鈥 said , a rheumatologist at Brigham and Women鈥檚 Hospital in Boston who was not involved in completing the review. 鈥淪o I鈥檓 not sure we learned something new … but it does give confidence that indeed there鈥檚 a good margin of safety and the risks are minimal.鈥

To complete the analysis, Alexander and his team studied overall patient outcomes, adverse events and whether patients had immune system reactions to the drugs.

Experts not involved in the analysis said that the authors did a good job, but they didn鈥檛 have a robust body of studies with which to work.

鈥淭hese are a patchwork of studies that show if you take the [original] drug and switch [to a biosimilar], that鈥檚 fine,鈥 said , a gastroenterologist at Massachusetts General Hospital in Boston who was not associated with the study, adding that the studies include multiple biosimilars and multiple disease indications and were completed mostly outside the U.S. 鈥淚t鈥檚 a step in the right direction.鈥

But he pointed out that the studies included in the analysis are small and the review doesn鈥檛 include many patients overall compared with other systematic reviews in general.

All told, about 1,400 people took part in clinical trials and more than 500 people were included in observational studies that made up the review. Those not involved in the study said these were low numbers on which to draw conclusions.

鈥淚t does raise an eyebrow,鈥 Yajnik said.

However, others said this limitation is to be expected considering how relatively new biosimilars are and how many years it takes to complete these studies.

鈥淧eople are thirsty for information about biosimilars and I鈥檓 sure that the journal felt an obligation to put out information,鈥 said Solomon, who is also a professor at Harvard University’s medical school.

Since their arrival on the market, biologics have been major moneymakers for drug companies. AbbVie saw its quarterly net revenue jump by 17.8 percent in earnings reported last week thanks to its biologic, Humira. And Remicade generated $1.2 billion in U.S. sales for Johnson &聽Johnson in the second quarter of 2016. Both drugs are聽TNF-alpha inhibitors.

But a single Remicade infusion can reportedly cost $1,300 to $2,500. That鈥檚 where experts hope biosimilars will provide lower-cost options to patients and providers.

鈥淏iosimilars will be cheaper than originators. The variation in terms of 鈥榙iscount鈥 is large, however,鈥 said Joshua Cohen, an economist at the Tufts Center for the Study of Drug Development. 鈥淚n Europe, we see biosimilars that are 10 percent cheaper and those that are 70 percent cheaper.鈥

The Food and Drug Administration approved its first biosimilar, Zarxio, which is used to treat chemotherapy-associated infections, in September 2015. And in April, the FDA approved the Remicade biosimilar Inflectra.

鈥淭hey really want to know that the molecules are almost identical,鈥 Solomon said, explaining the FDA鈥檚 evaluation is more about chemistry and pharmacology than it is about clinical trials. Still, the FDA requires one clinical trial for a single disease indication to prove biosimilarity, he said. No clinical trials are required for traditional generics, but, for typical new drugs, three phases of clinical trials are required before approval.

Inflectra has not yet launched in the U.S., but in Europe, where it was approved in 2013, it reportedly costs about 30 percent less than the original drug. Zarxio was about 15 percent cheaper than its precursor, Neupogen, when it launched in Europe in 2009.

Although Inflectra made it through the FDA approval process, Hopkins’ Alexander said it鈥檚 still important for researchers like him to complete systematic reviews of peer-reviewed literature and trial registries. He said his team鈥檚 analysis is 鈥渙ne of the most rigorous and comprehensive assessments鈥 of TNF alpha inhibitor biosimilars compared with original brand-name biologics.

Pharmacist Donald Miller, a professor at North Dakota State University, said the analysis is important because it is the first of its kind for these biosimilars. But the finding that the biosimilar drugs were 鈥渋nterchangeable鈥 with the originals is interesting because the FDA has not yet awarded this designation to either Inflectra or Zarxio.

鈥淚t is very important to realize that interchangeability of biosimilars has a specific meaning under U.S. law and [the] FDA has not yet issued guidance for any product to define itself as interchangeable to date,鈥 he said.

Miller said many physicians worry that insurance companies will force patients to switch from biologics to biosimilars to save money, risking reactions to the tweaked drug molecules. Indeed, the American College of Rheumatologists鈥 position statement says that patients should be informed if they鈥檙e switched to biosimilars to cut costs and their physician should sign off on it.

鈥淥ver time, biosimilars can save the health system billions, but only if they鈥檙e adopted and only if patients and clinicians and policymakers develop and support mechanisms that promote their adoption,鈥 Alexander said.

KHN鈥檚 coverage of prescription drug development, costs and pricing is supported in part by the .

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