Washington Editor

The FDA approved the biosimilar product Omnitrope (somatropin [rDNA origin]), a follow-on version of a growth hormone drug, in a landmark decision that reverberated among both supporters and opponents.

Many observers saw the approval as laying the groundwork for future FDA decisions, although for some time now, the agency has indicated that it would evaluate follow-on biopharmaceuticals on a case-by-case basis.

"It's a start," said Dennis Mondolino, a patent lawyer with the New York firm McDermott Will & Emery. "I think it's the beginning."

Omnitrope was developed by Sandoz GmbH, which expects a U.S. launch later this year. The Holzkirchen, Germany-based company sued the FDA last year over delays in dealing with the application, which was filed under Section 505(b)(2) of the Food, Drug, and Cosmetic Act. That permits approval on published scientific literature or on prior agency findings that similar drugs are safe and effective, making Omnitrope the first recombinant copy of a biotech drug to be approved in the pathway.

That is particularly significant to those seeking a quick mechanism for clearances of follow-on biopharmaceuticals. Generally arguing in favor of some testing to prove generic safety and bioequivalency, they advocate a process similar to the procedure for approving generic versions of small-molecule pharmaceuticals that are chemically synthesized - the abbreviated new drug application.

The Generic Pharmaceutical Association (GPhA) heralded the Omnitrope decision as "a significant first step" toward bringing more affordable biopharmaceuticals to the U.S. market, according to a statement by the organization's president and CEO Kathleen Jaeger, who later added that the approval demonstrates that the FDA "already has the authority to approve such products." The GPhA, based in Arlington, Va., has long contended that the agency has legal powers to act on generic biopharmaceutical applications via the 505(b)(2) process, in conjunction with authority under the Public Health Service Act.

But the FDA said its Omnitrope decision does not set a precedent, countering that new legislation would be needed to establish an abbreviated approval pathway under Section 351 of the Public Health Service Act, through which most protein products are licensed. The agency added that its approval does not signal that follow-ons could be approved for more complex or less well understood proteins cleared as drugs under the Food, Drug, and Cosmetic Act.

Such language suggests that the FDA is not inclined to open the door to mass approvals of follow-on biopharmaceuticals. Mondolino agreed, telling BioWorld Today that the decision would not "take effect immediately" and spur a sea change at the "historically conservative" agency that "marches to the beat of its own drum." But he noted that the approval hints that a mechanism for biosimilar applications could be coming in the next five years.

Jaeger said the GPhA would continue to call on Congress "to codify" the FDA's authority to approve generic biopharmaceuticals under the Public Health Service Act. The organization estimates that more than $10 billion worth of biopharmaceutical drugs will lose patent protection over the next five years.

Notably, the FDA declined to term Omnitrope a generic, instead stressing that is not therapeutically equivalent to or substitutable for any of the other approved human growth hormone products. Rather, it is "more appropriately characterized" as a follow-on protein product, an agency statement said.

Also, the agency countered assertions that Omnitrope is the first follow-on protein to receive FDA clearance, citing past approvals of GlucaGen (glucagon recombinant, from ZymoGenetics Inc.), Hylenex (hyaluronidase recombinant human, from Halozyme Therapeutics Inc.), Hydase and Amphadase (hyaluronidase, Prima Pharm Inc., and Amphastar Pharmaceuticals Inc., respectively) and Fortical (calcitonin salmon recombinant, from Unigene Laboratories Inc.).

Omnitrope's approval was based on reference to Genotropin, a human growth hormone product made by New York-based Pfizer Inc. Comparisons between the two were fairly simple because human growth hormone has several characteristics that enable one version to be adequately compared to another for purposes of a 505(b)(2) approval, according to an FDA statement. Its primary structure is known, it is non-glycosylated, clinically relevant bioassays and qualified biomarkers are available, there is a long and well-documented history of clinical use, its mechanism of drug action is known and its human toxicity profile is well understood.

The approval did not raise scientific issues associated with other protein products, principally those that are more complex in nature and have unknown or multiple active ingredients, unknown mechanisms of action, are more difficult to characterize or are glycosylated.

But that's not the case for other biopharmaceuticals, according to many in the biotech industry who contend that copycat products are impossible to come by, especially in the absence of rigorous testing to establish equivalence. Advocates also argue that because the production process cannot be duplicated, quick approvals should not be allowed. Because of that continuing opposition, Mondolino predicted numerous petitions by pioneer companies seeking to block biosimilar applications.

Pfizer filed one of the several petitions against Omnitrope in an attempt to stonewall its approval. But in early April, a federal judge ruled that the FDA must take action on the two-year-old application from Sandoz, the generic business of Basel, Switzerland-based Novartis AG.

Omnitrope's FDA clearance followed the product's approval in Europe, which came in April. Already it is sold in Germany, where it is priced 25 percent less than Genotropin, the reference drug. Additional Omnitrope launches are planned for later this year in Europe, where regulators have been more progressive in policies regarding follow-on proteins. It also is available in Australia.

Pricing for the U.S. has yet to be finalized, a Sandoz spokeswoman said.

The recombinant human growth hormone is indicated for the long-term treatment of children with growth failure due to an inadequate secretion of endogenous growth hormone, and for long-term replacement therapy in childhood- or adult-onset growth hormone deficiency in adults. Several other brands of human growth hormone already exist.

Sandoz said recombinant biotechnology medicines would play a key role in its growth strategy as the products come off patent in the coming years. The company is said to have another five biogenerics in development for unspecified indications.