German biopharma firm Sandoz has won a landmark first-of its-kind biosimilar drug approval in the US after a long battle with the US Food and Drug Administration (FDA). The decision could open the floodgates for generics manufacturers in this lucrative market.
Following the green light for Sandoz's copycat biologic growth hormone drug, Omnitrope, the company is now ramping up manufacturing at its fermentation plant in Kundl, Austria and expects to have the drug on the US market by the end of the year.
Omnitrope was approved in Europe in April by the European Commission and is already on the market in Germany, with launches planned in further European countries later this year. The drug was also launched in Australia in November last year.
According to the FDA Omnitrope is not officially called a generic because it is not rated as therapeutically equivalent to any of the other approved human growth hormone (hGH) products. It is however "sufficiently similar" to a product already approved and is thus given the term "follow-on protein product." In Europe the preferred term is 'biosimilar'.
The FDA has already approved several other follow-on protein products, however, Sandoz is hailing this latest approval as a breakthrough as Omnitrope is the first recombinant product that refers in its application to the prior FDA approval of an exisiting recombinant product (Pfizer's Genotropin).
"The other approvals refer to previously approved naturally-sourced or synthetic products," Sandoz spokesperson, Kurt Leidner, told In-PharmaTechnologist.com.
Expensive biotech medicines are quickly becoming favoured treatments for a range of diseases, including cancer and arthritis. Approximately one-fourth of new drugs coming on the market are biopharmaceuticals and annual sales are projected to surpass $52bn (€40bn) by 2010.
However, some of the biggest-selling biological drugs developed during the first phase of the biotechnology revolution in the 1980s have already lost or will lose patent protection in the next few years.
With a total value of $20.2bn in global sales, insulin, human growth factor, epoetin, colony stimulating factors, interferon alpha and interferon beta are all now susceptible to competition from biogenerics.
However, the FDA has so far been reluctant to approve copycat biologics because the challenges that the sophisticated manufacturing of biogenerics pose are creating significant regulatory hurdles.
Biogeneric active pharmaceutical ingredients (APIs) have to be re-developed using living cells, and so the right cell lines have to be found to produce an API that is as much as possible identical to the original supplier' s API, without infringing only one of the many application patents.
There is currently no approval pathway in place for such drugs in the US and the FDA dragged its heels making a decision about Omnitrope, only doing so after Sandoz took them to court and a federal judge ordered them to make a decision.
The FDA said it was able to approve the drug in this case because hGH is a fairly simple and well-understood protein and has several characteristics that enable one rhGH product to be adequately compared to another for purposes of approval.
hGH is well characterised and non-glycosylated; the primary structure of hGH is known, and physicochemical tests exist for the determination of an hGH product's secondary and tertiary structures; clinically relevant bioassays and qualified biomarkers are available for hGH; it has a long and well documented history of clinical use as a replacement for endogenous growth hormone deficiency; and hGH's mechanism of drug action is known, and its human toxicity profile is well understood, said an FDA statement.
However the FDA stressed that the Omnitrope approval "does not establish a pathway for approval of biological follow-on products, nor does it mean that more complex and/or less well understood proteins could be approved as follow-on products."
However, both Sandoz and the US Generic Pharmaceutical Association (GPhA) disagree and believe that the decision is a breakthrough in the fight to get an abbreviated approval process in place for such drugs, which would avoid the unnecessary duplication of animal and human clinical trials.
"This is a very important step in the right direction to having a pathway developed for biosimilar drugs," a spokesperson from the GphA told In-PharmaTechnologist.com.
"This proves that the FDA has the scientific knowledge to approve a "follow-on" protein drug and if they can approve one then there is no reason why they can't approve others as well."
Congress now needs to confirm that the FDA does in fact have the authority to approve biosimilar drugs and push them to establish a proper regulatory pathway so that the industry finally has some guidelines, said the spokesperson.
"An abbreviated approval process would open the floodgates for generics companies to develop biosimilars without the risk of a laborious and uncertain regulatory environment," he said.
In the meantime, Sandoz needs no further encouragement and is now busy developing five new follow-on protein products.