It's not every day that a multimillion-dollar market suddenly opens up, inviting all comers to the ground floor of competition. But that's exactly what happened when the FDA put out its "open for business" sign for biosimilars.

Even before the agency issued its first draft guidances last year on developing biologic copies and began meeting with interested sponsors, drugmakers were weighing their opportunities, developing strategies for entering the field and seeking out partners to strengthen their market position.

Now, as the regulatory path continues to evolve and the challenges of copying a complex molecule are being realized, some of those companies may be rethinking their strategies.

One of the biggest challenges in developing a biosimilar is recruiting enough subjects for a large clinical trial – a step that's not needed in the development of a generic small-molecule drug. The difficulty comes in the fact that, generally, patients enroll in a clinical trial in the hope of getting access to a new or improved therapy.

But biosimilars offer no improvement, so the only incentive for trial participation might be getting the drug for a little less, Craig Wheeler, president and CEO of Momenta Pharmaceuticals Inc., told BioWorld Today.

Adding to the recruitment challenge is the possibility that multiple biosimilar trials, based on one reference drug, could be vying for the same pool of subjects, he said.

That's a realistic expectation as early biosimilar development in the U.S. is focusing on blockbuster biologics, such as Abbvie Inc.'s Humira (adalimumab), that are coming off patent soon. According to the latest BioWorld Data report, The Biosimilars Game: A Scorecard for Opportunities, Threats, and Clinical Strategies, at least nine companies are pursuing biosimilar versions of Humira, which will lose patent protection on its composition claims in 2016.

Momenta, of Cambridge, Mass., would like to avoid the recruitment competition of large clinical trials in its development of up to six biosimilars partnered with Baxter International Inc. To do that, Wheeler said the company is focusing on a science-based strategy aimed at unlocking the structure of the targeted therapeutic proteins and creating thoroughly characterized biosimilars that are indistinguishable from the brand biologic.

Following the FDA's advice, Momenta is squeezing everything possible from the scientific evidence to reduce the need for large trials. But it may not be able to avoid them altogether. While the FDA hasn't released guidance on what would be needed to establish interchangeability, which is Momenta's goal, the agency has indicated switching trials will likely be necessary to demonstrate interchangeability. (See BioWorld Today, Feb. 10, 2012.)

Drugmakers hoping to compete in that new market are facing other challenges, as well. For instance, the cost and technical risk involved could force some companies to leave the fray. And the ongoing evolution of the path, which is literally being paved under the feet of the trail blazers, continues to create uncertainty, Wheeler said.

He also expects more uncertainty on the legal front when biosimilar developers and the makers of the reference products begin the patent information exchange dictated by Congress as part of the Biologics Price Competition and Innovation Act (BPCIA).

Rather than set up a biosimilar version of the Orange Book, which lists the patent claims for small-molecule drugs and is used by makers of generic drugs, the BPCIA created a complex schedule that requires a biosimilar applicant to provide the innovator with a copy of its application and other manufacturing-related information. The schedule also mandates time frames for exchanging lists of patents that may be infringed and those that could be licensed. (See BioWorld Today, June 29, 2011.)

Since the exchange doesn't take place until a biosimilar application has been filed with the FDA, no one knows yet how it will work in reality and whether it will spur as much litigation as Hatch-Waxman has done with generics.

Despite the challenges and competition from big pharma and biologics players, as well as generic giants, Wheeler thinks Momenta's science-based strategy will give the company a solid edge in a marketplace that could be crowded with biosimilars in the future.

To make his point, he compared the biosimilar market to the advent of the personal computer (PC). Everyone jumped into the PC market – the big technology companies like IBM and small start-ups that no one had heard of. Initially, the big players were expected to win the competition. But in the end, they were impeded by their efforts to protect their existing business, Wheeler said.

Just as the PC market was captured by young companies and start-ups, he predicted the biosimilar market will go to drugmakers that address its challenges as they would a new business, rather than being concerned about protecting their existing brands.

Editor's note: For a copy of BioWorld's biosimilars report, please contact the BioWorld Data account managers for exclusive introductory pricing at (800) 477-6307.