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.
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't 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 syndrome, 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 "interchangeable" with the original versions, such as Remicade and Humira. Their findings and an accompanying editorial were published in the Annals of Internal Medicine.
"We examined one very costly and commonly used class of biologic therapy," said study author Dr. Caleb Alexander, codirector of the Johns Hopkins Center for Drug Safety and Effectiveness. "The totality of evidence strongly supports the comparability of the biosimilar and branded product."
Although the analysis was reassuring, experts didn't find the results surprising.
"Honestly the data have been pretty consistent," said Dr. Daniel Solomon, a rheumatologist at Brigham and Women's Hospital in Boston who was not involved in completing the review. "So I'm not sure we learned something new ... but it does give confidence that indeed there's a good margin of safety and the risks are minimal."
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't have a robust body of studies with which to work.
"These are a patchwork of studies that show if you take the [original] drug and switch [to a biosimilar], that's fine," said Dr. Vijay Yajnik, 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. "It's a step in the right direction."
But he pointed out that the studies included in the analysis are small and the review doesn't 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.
"It does raise an eyebrow," 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.
"People are thirsty for information about biosimilars and I'm sure that the journal felt an obligation to put out information," 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 & Johnson in the second quarter of 2016. Both drugs are TNF-alpha inhibitors.
But a single Remicade infusion can reportedly cost $1,300 to $2,500. That's where experts hope biosimilars will provide lower-cost options to patients and providers.
"Biosimilars will be cheaper than originators. The variation in terms of 'discount' is large, however," said Joshua Cohen, an economist at the Tufts Center for the Study of Drug Development. "In Europe, we see biosimilars that are 10 percent cheaper and those that are 70 percent cheaper."
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.
"They really want to know that the molecules are almost identical," Solomon said, explaining the FDA's 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's still important for researchers like him to complete systematic reviews of peer-reviewed literature and trial registries. He said his team's analysis is "one of the most rigorous and comprehensive assessments" 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 "interchangeable" with the originals is interesting because the FDA has not yet awarded this designation to either Inflectra or Zarxio.
"It 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," 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' position statement says that patients should be informed if they're switched to biosimilars to cut costs and their physician should sign off on it.
"Over time, biosimilars can save the health system billions, but only if they're adopted and only if patients and clinicians and policymakers develop and support mechanisms that promote their adoption," Alexander said.
KHN's coverage of prescription drug development, costs and pricing is supported in part by the Laura and John Arnold Foundation.