- The U.S. Food and Drug Administration on Tuesday approved Novartis' biosimilar version of Amgen's blockbuster anti-inflammatory drug Enbrel (etanercept), marking only the third time the regulator has approved a biosimilar of a biologic drug.
- Approval for the copycat drug, which will be marketed as Erelzi, came swiftly on the heels of an unanimous recommendation by a key advisory panel last month.
- Importantly, the FDA okayed Erelzi for use across all five of Enbrel's approved indications. So-called 'indication extrapolation' has been a matter of debate as biosimilars become more common in the U.S.
A decision in favor of approval had been expected after the FDA's advisory panel voted 20-0 in support of Novartis' biosimilar. Still, the green light continues the positive signaling from the agency on continued development of biosimilar drugs.
While biosimilars are more common in Europe, the U.S. was slow to adopt a regulatory structure to permit approval for copies of biologic drugs, which are more complex than traditional small molecule treatments.
Erelzi is the second biosimilar successfully developed by Novartis' Sandoz unit, which hopes to launch five biosimilars of major cancer and immunology drugs by 2020. Sandoz, the generics arm of the Swiss pharma giant, also won approval for a copy of Amgen's Neupogen last year.
The European Medicines Agency is reviewing an application for approval of Novartis biosimilar entanercept in European markets, Novartis said.
Novartis will now have to give Amgen 180 days notice of commercial marketing to Amgen before it can begin to market Erelzi, a legal stipulation which was recently clarified in a court battle between the two companies. Another case, between Amgen and Canadian drugmaker Apotex, reaffirmed that notice can be provided only after the FDA approves a biosimilar.
But even following the 180 days, Novartis could be blocked from launching Erelzi due to ongoing litigation. Amgen sued Novartis in February for patent infringement and has sought an injunction to stop Novartis from marketing biosimilar Enbrel until all of its patents on the drug expire. In a recent note, Jeffries analysts thought it would be unlikely for Novartis to risk launching Erelzi before the lawsuit is resolved.
Biosimilar vs. interchangeable
Regulators in the U.S. approved Erelzi specifically as a biosimilar rather than as an "interchangeable product." This means the drug is highly similar to its reference product (Enbrel) with no clinically meaningful differences. Approval as an interchangeable would indicate Erelzi is expected to produce the same clinical result as Enbrel in any given patient.
While the distinction between the two categories appears to be a case of splitting hairs, classification as an interchangeable would allow pharmacists to make substitutions between the branded drug and the biosimilar, much as they do for generic copies of pharmaceuticals.
So far none of the three biosimilars okayed by the FDA have been classified as an interchangeable.
Erelzi will be allowed for use in patients with moderate to severe rheumatoid arthritis, moderate to severe polyarticular juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis and moderate to severe plaque psoriasis. The drug will also carry a boxed warning cautioning against the risk of serious infections, such as tuberculosis and invasive fungal infections.
Playing both sides
Novartis hopes to wrest away some of Amgen's revenues from Enbrel, which last year totaled roughly $5.4 billion. (Pfizer markets Enbrel outside of the U.S. and Canada). While the other two biosimilars, Zarxio and Inflectra, have so far had only modest launches, Erelzi represents a significant threat to Amgen. Sales of Enbrel account for about 25% of the company’s total sales.
Interestingly, Amgen is playing both offense and defense in the race to develop biosimilar versions of top-selling biologic drugs. Even as the drugmaker attempted to fend Novarts’ efforts to market biosimilar Enbrel, Amgen was developing a biosimilar version of AbbVie's Humira. That biosimilar won the backing of an FDA advisory panel the same week as Novartis' biosimilar Enbrel
Generic drugmakers have typically operated as distinct from their branded counterparts, although the lines have blurred in recent lines. By contrast, biosimilar development in the U.S. has been led by big pharma companies such as Novartis, Pfizer and Amgen.