Washington Editor

Editor's note: This is the second in a three-part series on different models for developing biosimilars. The final part will look at how a biotech start-up plans to enter the field.

Like their big pharma cousins, major generic drugmakers are wasting no time in hitting the biosimilar highway.

Several of them are already cruising in the European market and are just waiting for patents to expire in the U.S. – and for guidance from the FDA.

But some generic drugmakers see what industry considers as the first lap – proteins such as insulin and human growth hormones – as already too crowded internationally, so they're tooling their engines for the next big race, monoclonal antibodies.

That's the plan for Eden Biodesign Inc., of Liverpool, UK, which was acquired last year by Parsippany, N.J.-based Watson Pharmaceuticals Inc. to speed the generic-drugmaker's entrance into the biosimilar market. Eden is developing its own biosimilars and is eyeing partnerships, Eden President Roger Lias told BioWorld Today.

Eden's strategy also involves identifying potential therapeutic areas and products. Rather than scrambling for market share on a crowded roadway, the company wants to be the first with a biosimilar in a specific therapeutic area, Lias said.

There are a number of challenges, especially in the U.S., which, compared with other countries, is late in welcoming biosimilars.

Lias noted that although the regulatory path has been created, many of the details are missing.

For U.S. approval as a biosimilar, a product must be highly similar to the reference product (an FDA-approved biologic). While a biosimilar may have minor differences in clinically inactive components, there can be no clinically meaningful differences between the biosimilar and the reference product in terms of safety, purity and potency. Additionally:

• a biosimilar must use the same mechanism of action as the reference product;

• any indication for a biosimilar must have been previously approved for the reference product;

• the route of administration, dosage form and strength of the biosimilar must be the same as those of the reference product.

The big question is how the FDA expects drugmakers to demonstrate that biosimilarity. Drugmakers anticipate having to do some clinical trials. Although the FDA has indicated it wants to avoid unnecessary duplication of trials, how extensive biosimilar clinical development has to be remains an unknown.

For instance, if a reference product for a biosimilar has two different cancer indications, Lias wondered whether the biosimilar would need a clinical trial for each indication. He's hoping such questions will be answered in a guidance the FDA has promised to release soon.

Until the questions are answered, it's challenging to get a sensible deal structure with partners, Lias said.

However, he's confident the FDA will fill in the missing details in sufficient time for companies to gear up their biosimilars and have them ready when the patents begin to expire on the referenced products.

Marketing Challenge

Another challenge will be getting market share when competing against established biologics. Since biosimilars are not generics, they will not automatically be substituted for the brand biologic. That means companies will have to market their biosimilars in much the same way as a brand product, according to Robert Billings, interim executive director of the Generic Pharmaceutical Association. (See BioWorld Today, March 9, 2011.)

Marketing would be a new endeavor for generics companies. And the cost of maintaining a marketing team could add to the cost of biosimilars. For that reason, some generic drugmakers are pushing for biosimilars to have the same name and labeling as the referenced products – just like with traditional generics.

Having to use a unique name for a biosimilar would impede market competition, defeating the purpose of the abbreviated pathway in reducing drug prices, John Pakulski, head of U.S. regulatory affairs for Princeton, N.J.-based Sandoz Inc., said at a BIO 2011 session in June. (See BioWorld Today, July 26, 2011.)

But the FDA doesn't think that's a good idea as it would make it difficult to track adverse events to a specific product.

Lias isn't worried about market uptake, noting that biosimilars are becoming the trend in Europe, where 18 biosimilars had been approved as of a year ago. "We've already started, in Europe, to tip that balance" toward biosimilars, he said.

The use in Europe has been driven by physicians, who initially were resistant to biosimilars. A study of Danish and German doctors found that oncologists were the first to accept the follow-on drugs, Lias said. Other doctors then began to follow their lead.

In the U.S., insurance companies and government agencies will likely drive the use of biosimilars, due to the financial benefits the follow-ons offer, he added. Although biosimilars still would be expensive compared with traditional generics, they will be somewhat cheaper than innovative biologics that can cost thousands of dollars.

Lias projects the increased competition could eventually produce a 30 percent to 40 percent savings, accelerating acceptance of biosimilars. (See BioWorld Today, July 21, 2011.)

Speaking at the BIO 2011 session, Rachel Sherman, associate director for medical policy at the FDA's Center for Drug Evaluation and Research, acknowledged that biosimilars will have a different market paradigm than generics.

Consequently, she doesn't expect biosimilars to capture a huge part of the market like generics have, but she thinks there will be an economic incentive for developing them.

Lias agreed. "There are ways to make it work," he noted.