Is Expanded Access a Route to Biosimilars Mired in Litigation?

From 2013 to 2018, approximately 9000 patients received medicinal agents through the FDA’s expanded access program, which allows access to premarket drugs in cases of unmet need, but none have received access to biosimilars under this program, according to the FDA.

The FDA does not rule out access to biosimilars, either those in development or those already approved, through the expanded access program, although there is a strict set of criteria that must be met for patients to qualify. These include no acceptable alternative agents, no available clinical trials, a life-threatening condition, and risks of taking the agent are not unreasonable in the context of the disease or condition to be treated.

The question about using the expanded access program for access to biosimilars arose during a series of talks recently about patent thickets created around innovator products and the challenges posed to manufacturers of biosimilars in navigating these legal obstacles to get to market. Much of the appeal of using biosimilars through expanded access as opposed to the originator agents could conceivably derive from the cost-benefit ratio. Biosimilars are typically brought to market at lower cost than reference drugs. For patients facing financial toxicity, a biosimilar at a lower cost or available free of charge could be appealing.

Biosimilars are developed so that they are highly similar to original, or reference, products and have no meaningful clinical differences. Immunogenicity studies may be required for a biosimilar to achieve the ranking of “interchangeability” with the respective reference product; interchangeability is a designation indicating the agent can be substituted for the reference product at the pharmacy counter without consultation with the prescribing physician.

In the process of developing a biosimilar to obtain FDA approval and to launch the product on market, a substantial quantity of the agent may be accumulated that might reach its expiration date between the time the product receives the FDA stamp of approval and the time the sometimes formidable legal hurdles are overcome to do a product launch, noted Bruce Leicher, a legal advisor and former senior vice president and general counsel for Momenta Pharmaceuticals. Leicher served as the moderator during the series of talks in early March at the World Biosimilar Congress USA 2020 at the Festival of Biologics USA in San Diego, California.

“There’s a lot of product that may actually be OK that could go to waste. The question is, would it be infringing” on the originator’s patents to offer this product to patients through the expanded access program? he asked rhetorically.

In an interview, Noelle Sunstrom, CEO and founder of NeuClone, a biopharmaceutical company with a broad pipeline of biosimilar candidates based in Redfern, Australia, opined that in cases where financial toxicity was presented as a reason for seeking a biosimilar through the expanded access program, “it would have to be for very severe disease instances where there are no other viable treatment options except for the unaffordable originator.”

“It would also require the biosimilar company to have a commercial supply available as well as a nominated price that would warrant exceptional access,” she said. “Who would be able to decide what biosimilars would qualify for this?”

She noted that the FDA’s expanded access program is traditionally intended for patients with diseases for which all other alternatives have been exhausted except an investigational product that may hold some degree of benefit. If the FDA has approved the product, then “it’s now a question of legal proceedings as to when it can begin being sold to patients,” Sunstrom said.

In response to a media query, the FDA did not rule out the possibility that financial toxicity would be weighed by the agency as a potential reason given by a patient for seeking access to a biosimilar that hasn’t yet been launched versus its reference product. Instead, the FDA pointed to its standard criteria, described above, and said those would have to be met for access to be granted.

In the expanded access decision process, the FDA makes a decision whether expanded access will be allowed, but that decision also is made by the company that produces the drug. A company has a right to decide for itself whether it wants to make a product available outside of the clinical trials process.

Speaking about expanded access in a presentation at the Festival of Biologics, Christopher Robertson, a professor of law and associate dean for research and innovation at the University of Arizona School of Law in Tucson, said the expanded access dilemma for these development companies has traditionally been “should they be laser focused on getting through the FDA process and getting to market, where they can get reimbursement for potentially thousands of patients over decades in the future, versus providing access to 1 or 5 or 20 patients now.”

Companies must take care not to compromise the long-term prospects for a drug candidate. Traditionally, companies have had to worry that granting access to drugs in development outside of clinical trials would make patients less willing to enroll in clinical trials for these drugs, because they might end up with placebo instead of the experimental, active agent.

Another issue is that outcomes for patients receiving drug through expanded access are not intended to be factored into approval decisions, but the FDA may make exceptions to this rule, which means that there is potential liability for a company that makes product available that is associated with a patient outcome that is concerning for the FDA. “There ends up being a series of repercussions, market-based challenges, that Congress really can’t fix if bad news comes out of expanded access,” Robertson said.

Assuming those hurdles are not insurmountable for biosimilars in development and other experimental agents, there’s still the question of whether doctors and patients even know of the expanded access program or the agent in question and have the time and wherewithal to apply for access, Robertson said.

“The expanded access program really begins with the doctor and patient. And it begins with the doctor and patient typically approaching a company who has to decide whether it wants to provide product in this setting. Then the company and the doctor approach the FDA together for permission,” Robertson said.

“Physicians often don’t know about the existence about drugs that are early in the development process, or that preapproval is even possible. It still requires some effort by the physician to go out of his or her normal practice pattern to pursue expanded access or right to try,” he said. Right to try is a reference to a federal law and multiple state laws that allow access to drugs in phase I development without FDA approval.

Much depends on the size of the company and its ability to respond to expanded access requests, Robertson said. “In some situations, there are no additional units of a drug that they’re in a position to provide outside of clinical trials…And who even picks up a phone when a physician calls to gain access? You see huge companies creating expanded access programs, and they have the staff and training to do that, but for smaller companies it ends up being a challenge.”