AbbVie's chief executive, Rick Gonzalez, seems certain that Humira, the world’s biggest-selling drug, will not face biosimilar competition until 2022. Amgen begs to differ.
The California group has submitted its data package for ABP 501 to the FDA, an event that starts the countdown to the legal wrangling over intellectual property that accompanies biosimilars’ march toward approval. Launch of a Humira competitor will be a seismic event for both AbbVie and pharma innovators, so this will be a closely watched case for the largely untested US pathway.
ABP 501 will join the FDA approval queue alongside biosimilars of Remicade, Enbrel and three of Amgen’s own products, Neupogen, Neulasta and Epogen.
One Neupogen lookalike called Zarxio, from Novartis, was launched in September. That came six months after FDA approval because a US court interpreted a commercial notice provision in US law as being the date of approval, as Amgen had argued, not the date of regulatory submission, as Novartis had insisted (End of the patent dance leaves Sandoz with six-month delay, July 22, 2015).
Taken together, these five products have $16bn in US sales at risk, compared with Humira’s $8bn, demonstrating how large Amgen’s bid to steal AbbVie’s revenue looms over the sector, not to mention how Amgen is trying to get its own back by going after bigger prey.
It also explains AbbVie’s pledge to fight to the death over Humira, as the rheumatoid arthritis treatment constitutes 64% of the group’s 2015 worldwide sales of $22bn, according to EvalautePharma’s consensus.
Unlike the slow burn of Europe, biosimilar development has burst into a wildfire in the US. The late development of a regulatory framework has meant that just 18 months have passed between first submission of a biosimilar and first lookalike monoclonal antibody in the US. In Europe seven years passed between the first biosimilar approval and that of an antibody.
Premium pricing is a vulnerability of biological agents in the US, and explains the eruption of interest. All told, there are 69 programmes targeting 17 products in the US, according to an analysis by Bernstein Research’s Ronny Gal. Of those in the biosimilar sector’s sights, eight are antibodies, including Roche’s cancer treatments Herceptin and Avastin.
With Zarxio’s approval and launch, much of the ambiguity of the US regulatory pathway has been resolved, although it should be noted that little news has emerged about three new biosimilar applications: Celltrion’s version of Remicade, submitted in August 2014, Pfizer’s version of Epogen, submitted in January, and Apotex’s version of Neulasta, submitted in February.
It is hard to say why the FDA has not scheduled an advisory committee or taken any approval action on these projects. Generic names, the use of the advisory committee process and the potential for some of these biosimilars to be deemed interchangeable by pharmacists could be behind the hush, Bernstein’s Mr Gal wrote.
Legislating from the bench
Less clear is the legal outlook. The Zarxio approval and launch resolved some of the early dispute – namely, the issue of commercial notice and the biosimilars makers’ patent disclosure requirements – but the strength of the innovator companies’ patent estates has yet to be truly tested.
This was behind AbbVie’s claim that Humira will stand until 2022 (Read my lips: no Humira biosimilars until 2022, November 2, 2015). The composition of matter patent, the strongest for any drug, expires at the end of 2016. Subsidiary indication and methods patents do not start falling until 2022, with a manufacturing patent that goes out to 2034.
While US courts have ruled that biosimilar makers are not required to disclose their manufacturing methods to the innovator companies in advance of approval, a procedure known as the “patent dance”, the innovators can obviously seek them in standard litigation, of which AbbVie’s Mr Gonzalez has seemingly promised plenty.
With so much at stake, the legal fight for Humira’s future could be the main defining moment in establishing the biosimilar market. AbbVie will fight every point, and the rulings might effectively set US law.