Will Originators Mimic Embrel?
Another major mAb therapeutic is Pfizer and Amgen’s Enbrel. This anti-TNF mAb is approved for a number of diseases including RA, psoriasis, and arthritis and goes off patent in October 2012. Merck is targeting Enbrel through a collaboration with Korean firm Hanwha Chemical.
A Phase III study under way in Korea is comparing Hanwha’s version of Enbrel called HD203 with Enbrel as combination therapy with methortrexate to treat RA. Clinical trials with HD203 have yet to be initiated in the U.S.
Under terms of the deal Merck will carry out clinical development and manufacturing of HD203 and has rights to commercialize the drug globally, except in Korea and Turkey, where Hanwha has retained marketing rights. The June deal committed Merck to paying up to $720 million for Hanwha’s copy of Enbrel.
At least in the case of Enbrel (etanercept), however, a real show stopper for biosimilar companies may have emerged that has nothing to do with the awaited regulatory guidelines. If the “submarine patent” principle holds, other torpedoes may lurk to thwart biosimilar antibody developers.
On November 22, Amgen reported that the patent for the fusion protein that is Enbrel (U.S. Patent No. 8,063,182) had just been extended by 17 years; Enbrel is owned by Roche and exclusively licensed to Amgen. Immunex, acquired by Amgen in 2002, originally licensed this patent application from Roche in 1999. In 2004, Amgen paid Roche a one-time fee and obtained an exclusive, fully paid-up license to the application.
In a statement to GEN, Amgen said, “we have patents related to particular methods of making Enbrel, Enbrel formulations, and methods of treatment that provide protection against Enbrel biosimilars. This newly issued patent to the fusion protein that is etanercept adds to that patent protection.
“We are confident in our ability to protect our products and, as we previously stated, we do not envision Enbrel biosimilar competition in the United States for the foreseeable future.”
An analysis by Geoffrey Porges and his group at Sanford C. Bernstein found that indeed Amgen has a formidable piece of IP to defend against the incursions of biosimilar competitors. The analysts said that based on conversations with the three involved parties, Roche, Amgen, and Pfizer, sunsetting of Amgen’s profit-sharing obligation on Enbrel to Pfizer in the 2013–2015 period is unaffected by this patent, and Roche is not entitled to any royalties on Enbrel now or in the future.
Enbrel had been talked about as one of the first complex biologics likely to appear in a biosimilar form, with protection assumed to expire in late 2012 in the U.S. and in 2015 in Europe. If Amgen’s patent sticks, it could keep Enbrel biosimilars off the market until at least 2028. Biosimilar companies with large stakes in antibody development, however, are still likely to challenge the ’182 patent or come up with ways to circumvent it.
While originator companies will look for ways to protect their patent turf, biosimilar firms will keep an eye on the potential profits to be had with these follow-on biologic products. We can expect companies to join forces as needed to gain a foothold in the market and battles that will provide good livings for lawyers for a long time to come.
Will Amgen be able to defend against the incursions of biosimilar competitors for Enbrel?