Federal Ruling Offers Some Regulatory Clarity For Biosimilars
By Trisha Gladd, Editor, Life Science Connect
On July 21, 2015, the Federal Circuit reached a momentous decision in the case of Amgen vs. Sandoz. The case, which has been closely watched by the biopharma community, began last October when two issues arose during the process of bringing Sandoz’s Zarxio, the biosimilar version of Amgen’s Neupogen, to market.
The first is regarding the requirements around what is known as “the patent dance.” This is the term used to describe the disclosure and information exchange provision in the Biologics Price Competition and Innovation Act (BPCIA), which details a patent review process between the original manufacturer of a drug and the manufacturer of the drug’s biosimilar. Sandoz felt the use of the word “shall” throughout the document indicated the provision was optional, therefore they did not engage in this process with Amgen. The second is regarding when the original manufacturer of a drug is given a 180-day pre-launch notice by the biosimilar manufacturer. Sandoz interpreted the law as stating that the notice can be given at the time the FDA accepted their biosimilar application, while Amgen felt it couldn’t be given until the FDA approved the biosimilar product for licensure. In March, the Northern District of California ruled in favor of Sandoz on both issues. After two appeals by Amgen, the Federal Circuit reviewed the case, announcing its ruling last week.
The court, which was split 2-1 on both decisions, confirmed Sandoz’s interpretation of the patent dance, which is that it is optional. In regard to the 180-day notice, they sided with Amgen by concluding that “an applicant may only give effective notice of commercial marketing after the FDA has licensed its product.” The significance of this ruling goes well beyond the rights of these particular manufacturers, as the decision marks the first step toward clarifying the regulatory path for U.S. biosimilar manufacturers.
What Does This Mean To Biosimilar Manufacturers?
Bert Liang, CEO of Pfenex, a biosimilars developer and producer, felt the patent dance ruling was a significant victory for companies pursuing biosimilars. “As you can imagine, it is a very big deal to have to hand over all of that confidential information,” says Liang about the product and manufacturing process information provided during these exchanges. “You’re giving a roadmap to the reference product developer, or the reference product sponsor, of what you’ve done.” Making it optional gives biosimilar manufacturers the choice as to whether or not they want to divulge their company secrets. However, if there is a situation where they aren’t sure if a patent is being infringed, they now have the ability to work with the original manufacturer to avoid litigation down the road.
In regard to the 180-day pre-launch notice, Pfenex voiced caution about the ruling in a statement released almost immediately after the decision was announced. This is due to the fact that the ruling gives “the reference product manufacturer” (original drug manufacturer) six more months “of diminished competition following a biosimilars approval, thus minimizing both the cost savings and patient access which biosimilar products provide.” However, despite the company’s reservations about the second part of the ruling, Bert Liang, CEO, echoes Judge Chen’s sentiment (one of three judges who ruled on the case) that this just means a biosimilar manufacturer would have the ability to time their development to coincide with the 180 days. “You could look to see when, for example, patents would expire and then time your six months before the patent expires," explains Liang. “It’s not optimal, especially for some of those products that do not currently have an upcoming intellectual property expiry, but, in general, there is a backup of development programs. Producers can take into account these 180 additional days that they’re going to wait before they can launch.”
Where Do We Go From Here?
Liang says that while he’s encouraged that the FDA has taken this first step, there is still a long way to go. “I think one of the issues we really need to get clarity on is how biosimilars are named,” says Liang. “This is something that needs to be done sooner rather than later.”
He lists several areas where additional clarification is needed, including extrapolation (the use of data from a set of indications that the biosimilar is developed for and consequently applying that data to other indications under which the reference product is approved) as well as interchangeability of biosimilars and the original drug at the physician and pharmacist level. In addition, knowing how the agency looks at and interprets bioanalytical tests will give them an indication of what level of bioanalytical characterization allows for minimization of clinical studies. “We really need to see guidance on all of these issues in order to be able to better understand what the regulators are expecting from developers going forward,” says Liang.
However, he recognizes that the U.S. biosimilar market is young and many of these answers will come with time. Learning from those who have walked this path before us will serve as a crucial key in forging a path for biosimilar developers to deliver much-needed cost savings to those who need these drugs. “I hope that our regulators will continue to garner lessons from Europe because they have the most mature market and have been able to establish this particular marketplace in the most robust way for patient access.”