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The next few years will see the healthcare industry bracing itself for new biosimilar products for a range of illnesses from oncology to rheumatoid arthritis.
On March 23, 2010, former President Obama signed the Patient Protection and Affordable Care Act (ACA) into law, which amended the Public Health Service Act to create an abbreviated licensure pathway for biological products that are demonstrated to be biosimilar to or interchangeable with an FDA-licensed biological product.
According to the FDA, a biosimilar product is a biological product that is approved based on a showing that it is highly similar to an FDA-approved biological product, known as a reference product, and has no clinically meaningful differences in terms of safety and effectiveness from the reference product.
The FDA defines an interchangeable biological product as a product that is biosimilar to an FDA-approved reference product and meets additional standards for interchangeability. If deemed interchangeable, a biological product may be substituted for the reference product by a pharmacist without approval from the prescriber.
There are currently five FDA-approved biosimilars in the U.S., the first of which was Zarxio (filgrastim-sndz) a biosimilar of Neupogen (filgrastim), approved in March 2015.
In June, the Supreme Court unanimously agreed to remove the six-month waiting period for biosimiliars. This will allow companies to begin launching their product as soon as they receive FDA approval. This change in timing will provide patients faster access to the medication and eliminate the additional exclusivity that companies were receiving as a result of time between approval and launch.
“The next few years will see the healthcare industry bracing itself for a barrage of new biosimilar products for a range of illnesses from oncology to rheumatoid arthritis-with pain medications on the horizon,” says Julie Rubin, director of clinical services at CompleteRx.
Approvals of biosimilars for the hematopoietic agents, Neupogen, Neulasta (pegfilgrastim) and Procrit/Epogen (epoetin alfa), are expected in the near future along with biosimilars for antineoplastic agents, Herceptin (trastuzumab), Rituxan (rituximab), Erbitux (cetuximab) and Avastin (bevacizumab).
Legal battles and FDA rejections are slowing down the approval of many biosimiliars, according to Rubin.
Recently, the FDA rejected Coherus’ biosimilar for Amgen's Neulasta. “Neulasta is a bigger and more complex biologic and to date, hasn’t been able to convince the FDA of its biosimilarity which is why the federal body has requested more information from the manufacturers such as the need for a reanalysis of some patient samples using a more specific assay as well as other manufacturing-related process information,” Rubin says.
Biosimilars present an opportunity for cost savings in managed care, but the degree of savings will depend on physician prescribing behavior, biosimilar pricing and finalized guidance from the FDA on interchangeability, explains Lindsay Bealor Greenleaf, director at ADVI, a healthcare consulting firm that advises life science companies and provider organizations.
“Up to this point, biosimilars, on average have provided only a 15% discount to the brand name products,” says April Kunze, senior director, clinical formulary development and trend management strategy at Prime Therapeutics. “If multiple biosimilars are available for a brand name product, we should see deeper discounts to both the brand name and biosimilar products in the future.”
Efficacy, safety issues
According to the FDA, the agency requires licensed biosimilar products to meet the agency’s rigorous safety and efficacy standards, which means patients and health care professionals can rely upon the safety and efficacy of the biosimilar product, just as they would the reference product.
While biosimilars are highly similar to their reference products, no biosimilar in the U.S. has been approved as interchangeable and without the interchangeable designation, a pharmacist cannot substitute the biosimilar without a new prescription from the prescriber.
“Managed care can direct the patient and/or prescriber to the equally effective and discounted product through utilization management,” says Kunze. “This will require education to both members and prescribers regarding the safety and efficacy of the biosimilar product relative to the originator.”
Unlike generics, which are chemical in nature, biosimilars are genetically engineered with a more complex structure. This means any slight change in their manufacture could result in notable variances in the makeup of the product, according to Rubin.
“As a result, patients may be more susceptible to minor side effects or allergic reactions that ordinarily wouldn’t arise with the reference product,” she says.
Although the risk exists, Rubin explains that occurrences of such reactions from biosimilars currently available to patients have been minimal, and the rigorous safety checks and balances in place should give professionals the confidence that these drugs are as safe and effective as possible.
Regulatory, legal barriers
The main regulatory issues related to biosimilar products include interchangeability guidelines, appropriate product labelling, and pharmacist substitution policies.
The FDA recently released draft guidelines on the evidence required to demonstrate interchangeability, and according to Greenleaf, stakeholder reaction to the guidance has been mixed, with biosimilar applicants asking the FDA to clarify that while interchangeability may require additional data, it does not represent a higher standard for the product itself.
Meanwhile, Patients for Biologic Safety and Access (PBSA) argues that the FDA ‘must abide by clear congressional intent’ by requiring a high standard of approval for interchangeability.
The FDA also issued guidelines earlier this year explaining how new biological products should be labeled. However, those biosimilar medications already being used by patients don’t necessarily meet the new guidelines, therefore work must be done to implement these guideline to the previously approved biosimilars.
According to Kunze, many states have passed legislation that requires a pharmacist to obtain physician and/or member approval prior to substituting a biosimilar, even if the biosimilar is deemed interchangeable by the FDA. This differs from current regulations regarding Abbreviated New Drugs Applications (ANDAs), or generics, which allows pharmacist substitution in many states.
If the decision is made that biosimilars can be interchanged the same as generics, pharmacists will need clear guidelines to follow to be sure a consistent approach to pharmacist substitution is taken across the country, explains Rubin.
Another hurdle that biosimilar manufacturers must overcome is that, under current law, beneficiaries are likely to pay more for biosimilars than for the reference product under Part D if they reach the coverage gap, according to Greenleaf.
“This discrepancy results from the ACA requirement that manufacturers provide discounts for branded drugs purchased in the “donut hole,” but not for biosimilars,” Greenleaf says. “As manufacturer discounts count toward the coverage gap’s out-of-pocket threshold, beneficiaries will exit the coverage gap faster by purchasing a branded product over a biosimilar.”
Current knowledge gaps
“Although highly publicized, there are many unanswered questions regarding the use of biosimilars in the U.S. and there needs to be good education on the approval process and safety/efficacy standards applied by the FDA,” Kunze says. “As the U.S. gains more experience with biosimilars and comfort level increase, there will likely be an increase in utilization and as utilization increases, there will be additional safety and efficacy data available which will help close the knowledge gaps.”
The potential for physician reluctance to use biosimilars over a reference product is an issue, but manufacturers are overcoming this hurdle with education efforts, Greenleaf says.
Even though the biosimilars on the market have been rigorously trialed and approved, data is still being collected on how these agents compare to the original, according to Rubin.
“While we don’t expect any of the new data for currently available drugs to significantly change our view of them, as more information becomes available, it is important that healthcare professionals stay abreast of any new findings and communicate effectively with each other and patients,” she says.
Erin Bastick, PharmD, RPh, is a staff pharmacist at Southwest General Health Center in Middleburg Heights, Ohio.