Second Etanercept Biosimilar Receives FDA Approval

Samsung Bioepis scored another biosimilar approval in the US, as the Food and Drug Administration gave its nod to etanercept-ykro on April 25, 2019. Formerly known as SB4, Samsung Bioepis dubbed this agent Eticovo™. It is the second
Enbrel® biosimilar to to receive US approval.
This approval covered all of the reference product’s autoimmune indications, including ankylosing spondylitis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis, plaque psoriasis, and rheumatoid arthritis. Clinical studies were performed in patients with moderate-to-severe rheumatoid arthritis, finding that in combination with methotrexate, Eticovo achieved ACR20 scores that were equivalent to that of Enbrel by week 24 (78.1% vs. 80.3%, respectively). Safety and immunogenicity were also comparable with those of the reference agent.

Eticovo has been approved in the EU and Canada, in addition to other parts of the world, under the brand names Benepali and Brenzys. Samsung Bioepis has not announced a launch date in the US for its biosimilar, and this can be delayed for quite some time. Sandoz’s Erelzi® was approved in 2016, but has not yet reached the market because of patent litigation. Amgen, which manufacturers Enbrel, believes its patents extend effectively into 2028, which would provide for nearly 30 years of product exclusivity.

Both Coherus and Lupin have investigational etanercept biosimilars that are in phase 3 trials. Neither has publicly filed for FDA approval to date.

Frustration Mounts as Sandoz’s Etanercept Biosimilar Launch Delayed into 2018

Call it irritation, exasperation, or frustration, but biosimilar manufacturers and payers alike are feeling it, as the fight over drug patents has barred the way to approval for yet another biosimilar for a costly biologic.

In this case, Sandoz’s Erelzi™, which was approved by the Food and Drug Administration on August 30, 2016, has been caught in the patent litigation web. The originator drug, Amgen’s Enbrel® was first approved in 1998. Amgen asserts that its patent on the agent protects exclusivity until 2029, which would give Amgen 31 years of sole marketing rights. Despite the unlikely event that it can defend its patent for this extraordinary period, Sandoz has acknowledged that it will need to hold off launch of the biosimilar until at least 2018.

In a report from Reuters on January 25, Richard Francis, CEO of Sandoz, stated that the legal battle “won’t really reach a conclusion until 2018. That’s the frustration sometimes of the legal situation, but the way I look at that, we’re carving the landscape out as we go.”

Indeed, Sandoz has been at launch-delaythe forefront of legal battles, also fighting Amgen on the validity of the 180-day notification period, which is now being readied for US Supreme Court arguments in the Spring. The 180-day notification period for Erelzi was due to end in
late February 2017. After this time, Sandoz may still launch the product, at risk of financial penalties and loss of revenues, if the courts rule that Amgen’s remaining patent is valid.

However, the potential for savings on Enbrel, through biosimilar competition, continues to be a mirage for payers. The agent, which pulled in US revenues of $5 billion in 2015, has been the subject of numerous recent price increases. Health plans and insurers, while believing these costs untenable, may have little choice but to pay up or find ways to more aggressively restrict access.

FDA Approves Amgen’s Adalimumab Biosimilar, but “–atto”?

The news of FDA’s approval of Amgen’s Amjevita™, a biosimilar of adalimumab, was widely expected. It came late in the afternoon on September 23rd. Extrapolation for this agent was widely approved by the FDA, matching the indications for Abbvie’s Humira®. After all, it was the logical outcome after a 26-0 vote in July by the Arthritis Advisory Committee to recommend approval.

We may not see this product on the market for a very long time because of patent litigation, but I harbor a bit of hope that by the time of launch next year or even in 2020, the FDA will have chosen a reasonable rule for naming these biosimilars.

The nomenclature the FDA is using makes such little sense, but I I assume this to be temporary, The FDA has not yet released its final guidance on the matter. However, the horse left the barn months ago. Whatever FDA decides, they should have finalized it before approving 4 biosimilars.

So far, here are the FDA’s nonproprietary names, in order of approval:

  • Zarxio® — filgrastim-sndz (Sandoz)
  • Inflectra® — infliximab-dyyb (Celltrion/Pfizer)
  • Erelzi™ — etanercept-szzs (Sandoz)
  • And now: Amjevita™ — adalimumab-atto (Amgen)

Whereas -sndz is obvious, the rest are nonsense. I never thought I’d say this, but the strange, cobbled together syllables comprising brand names make as much sense as these suffixes. It would have been just as easy to provide somewhat reasonable designations. Not everything can be as basic as sndz, but even giving all of them alfa, beta, zeta designations could have indicated their order to the market.

At some point in time, the FDA will have to place its bets on one the red or black side of the roulette table and take heavy criticism from branded or biosimilar manufacturers, professional groups, and/or payers.

All that can be said today is that the agency seems set on a 4-character suffix, going so far as asking biosimilar manufacturers to contribute 10 preferred suffixes themselves (but even that suggestion was retracted by the agency).

Whether you approve of the suffixes or not, you probably agree that FDA ought to commit itself to one rule at this point. Whether that rule must be applied to all biologics (including reference products retroactively) is another, perhaps more perplexing, problem.

First New Enbrel® Biosimilar Approved by FDA

Sandoz received approval by the Food and Drug Administration to market its biosimilar version of Enbrel® on Tuesday, August 30th. The FDA is calling this agent etanercept-szzs. It is the first biosimilar for etanercept approved for use in the US.

Sandoz has branded the product Erelzi™, and it is indicated for each of the autoimmune disorders for which the originator is approved, including rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and placque psoriasis.

Under current law, Sandoz could start marketing its new product 180 days after the FDA approval, which would mean a Q1 2017 launch. However, the patent litigation that has plagued many of the biosimilar agents may well delay launch of this agent. On August 11, the US District Court issued an injunction that precludes any manufacturing, distribution, or marketing efforts by Sandoz. Interestingly, Sandoz consented to the preliminary injunction. The court case associated with this patent wrangling is not scheduled to be heard until April 2017, and the decision may take some time after this. One wonders (1) how much additional revenue Amgen may rack up through the court date and (2) if Sandoz will take a much more aggressive discounting stance than it did with its first biosimilar Zarxio®.