Momenta Signs Licensing Deal With Abbvie. Did It Have a Choice?

We previously reported that Momenta Pharmaceuticals reevaluated its biopharmaceutical strategy going forward, deciding to move forward only with its investigational adalimumab and aflibercept biosimilars. Yesterday, Momenta announced that it has joined the long queue of pharmaceutical manufacturers signing a biosimilar licensing deal with Abbvie, which will allow commercialization of M923, its biosimilar to Humira, should it obtain regulatory approval. Momenta’s licensing deal is the fifth one signed by prospective biosimilar marketers in the US.

This agreement was pretty much a no-brainer for Momenta. The company did not have the stomach for attempting either an extended patent fight or an at-risk launch. However, the biosimilar licensing agreement only allows Momenta to market its adalimumab biosimilar in the US after December 2023, which will make it the fifth Humira biosimilar that will launch under the licensing agreements (Table). The main patents for Humira have expired in Europe, and these agreements have generally allowed the European launches to occur as of October 16 of this year.

Of the manufacturers signing biosimilar licensing deals with Abbvie , only Amgen and Sandoz have earned FDA approval for Amjevita® and Hyrimoz®, respectively. And Boehringer Ingelheim is still duking out patent litigation with Abbvie in the courts over its approved biosimilar agent Cytelzo®, for which it hopes to receive an interchangeability designation. The second through fifth agents entering the fight will be likely pounding away at subsequently smaller slices of revenue.

Perhaps the most frustrating part is that Abbvie is running a lucrative game; it will collect royalties from all of these manufacturers in 2023 and beyond, which will help offset declining marketshare from its biggest revenue contributor.

 

In Abbvie’s Web: Who Has Signed Licensing Agreements for Biosimilar Adalimumab?

Company/Partner

Drug Name

Launch Date

Amgen

Amjevita*

January 2023

Samsung Bioepis/Merck

SB5

June 2023

Mylan/Fujifilm Kyowa Kirin Biologics

Hulio

August 2023

Sandoz

Hyrimoz*

September 2023

Momenta

M923

December 2023

*Received FDA Approval.

Note: This post was revised and corrected, November 8, 2018.

Tidal Wave of Pegfilgrastim Biosimilars About to Hit Europe

We had mentioned the upcoming deluge of adalimumab biosimilars aiming to hit the European market in mid-October, but another biosimilar tidal wave may actually precede this.

The European Medicines Agency (EMA) has had an extremely busy week in the pegfilgrastim biosimilars arena. In addition to granting marketing authorization to Coherus Biosciences for its pegfilgrastim biosimilar, it has also approved the marketing of Pelgraz®, a pegfilgrastim produced by Accord Healthcare. In addition, the EMA’s Committee for Medicinal Products for Human Use has also recommended approval for three pegfilgrastim biosimilars—from Sandoz, Cinfa, and Mylan.

Mylan is the only drug maker with a marketed biosimilar version of pegfilgrastim in the United States. Its product Fulphila® hit the US market in early July. Coherus’ product, Udenyca™, is awaiting a November 2 decision from the Food and Drug Administration. Coherus is reportedly looking for a partner to market its pegfilgrastim biosimilar overseas, while it intends to market the product internally in the US. This means that Accord may have the first pegfilgrastim biosimilar to reach patients in the EU, though this advantage will be short lived should Mylan in particular gain approval.

In other biosimilar news…Boehringer Ingelheim announced positive results in its clinical study of Cylteza® versus Humira® in patients with moderate-to-severe plaque psoriasis. The study results were announced at the European Society of Dermatology and Venereology.

Samsung Bioepis Co., Ltd. announced that the FDA has accepted its 351(k) application for SB5, a biosimilar to adalimumab. Samsung is the fourth manufacturer seeking to enter the biosimilar market for Humira. Two have been approved (Amjevita® by Amgen and Cyltezo® by Boehringer Ingelheim) but are not yet marketed. A decision on Sandoz’s application is expected later this year.

With the Samsung Bioepis Deal, Abbvie Tightening Its Grip on the US Adalimumab Market

Samsung Bioepis and Biogen has reached a deal with Abbvie that would enable it to market its biosimilar adalimumab (should it be granted approval) in June 2023. This is the second deal Abbvie has made with a potential competitor, confirming the solidity of its patent wall. The European patent expires in October 2018, and competitors will be able to sell biosimilars over the pond unhindered at that time.

However, without competition, most expect unencumbered price increases until a US biosimilar introduction. In other words, biosimilars will not make an appreciable impact on the cost of adalimumab in the US market, unless another biosimilar manufacturer decides to launch at risk in the near future.

A Deal Prior to FDA Approval

The agent, SB5 has not yet been filed for approval in the US. Samsung filed its application for approval in the EU in July 2016 and was authorized by the European Medical Agency in August 2017. Biogen will market the agent for Samsung, whenever it is launched.

Amgen inked a deal with Abbvie in September 2017, effectively ending its patent battle. This deal gives Amgen a jump on other competitors that reach settlements with Abbvie, by allowing a launch in January 2023. In addition, other manufacturers are working on adalimumab biosimilars, including Coherus and Sandoz. The biggest question though is Boehringer Ingelheim’s move, as they have the only other FDA-approved adalimumab biosimilar approved on the marketplace (but also unlaunched). Boehringer responded to our request but declined to comment on its plans mAbbvie produces Humira (adalimumab)oving forward with the product, including a targeted launch date.

Without Competition, Expect 45% Jump in WAC Price 

As addressed earlier in this space, the time to effective competition for a US biosimilar adalimumab is crucial. Abbvie’s annual global revenue on the product may reach as much as $21 billion, with the last price increase registered in January, at 9.7%. Assuming Abbvie sticks to its pledge of no more than one

10% price increase per year, that would result in a wholesale acquisition cost (WAC) of more than $52,000 at the close of 2022, or a 45% jump from today’s WAC. This figure does not reflect individual negotiated rates (including rebates) that health plans and insurers actually pay. Yet, it does roughly indicate what type of discount will be necessary when biosimilars reach the market to simply attain the cost paid in 2018—that is, no more savings. Without competition before 2023, this may be the one area where payers pray for a rapid and bracing race to the bottom on price once 2023 rolls around. With Abbvie’s hand continuing on the tiller, don’t plan on it.

In other biosimilar news…Celltrion acknowledged that it is seeking to rectify the manufacturing plant issues that torpedoed its FDA approval of biosimilars for trastuzumab and rituximab. In the statement, it noted, “Celltrion is confident that the issues raised by the FDA will be resolved in a timely manner.

We can confirm that the resubmission will be in-place relatively soon. Then, we are expecting approvals in 6 months after resubmission according to regulatory timeline.”

Budgeting the Impact of Inflectra and a Possible Clinical Benefit for Amjevita

Although the biosimilar marketplace is fairly stagnant at the moment, there was plenty of action at this week’s annual meeting of the Academy of Managed Care Pharmacy held in Denver, March 27–30.

Calculating the Breakeven Point for a Health System

A poster presentation from the University of Pittsburgh School of Pharmacy discussed the budget impact of adding biosimilar infliximab (Inflectra®) to the formulary of a model health system.

In this presentation, the researchers assumed the health system had 1,000 patients taking infliximab; of these, 400 were new prescription starts for the biosimilar’s rheumatology and gastroenterological indications, and the rest were receiving maintenance therapy on the originator product Remicade®. The model assumed 3 levels of discounting on Remicade: 10%, 15%, and 20%. They assumed that 60% of patients with a gastrointestinal indication would start on Remicade, and 40% of new start patients would be given Inflectra. At a new start and maintenance price of $20,430 for the biosimilar, they calculate a breakeven point of 15% discount for Remicade to keep only the originator on formulary.

If they assumed that the biosimilar was given not only to new starts but also to 50% of patients initially receiving Remicade , the breakeven discounting point for keeping Remicade only on the formulary becomes far greater. This model is somewhat conservative, because it assumes no further discounting by Pfizer for its biosimilar product. However, it also does not consider additional levels of rebating by Janssen Biotech.

A Biosimilar’s Noneconomic Benefit?

Although biosimilar manufacturers are constrained in the respect that their product has to not only mirror the structure and clinical effect of the originator biologic, it also cannot be produced in a more convenient form of administration (autoinjector vs. vial/syringe). The expectation is that the biosimilar will not be superior in any way to the originator. In a second poster presentation, Amgen researchers disputed this assertion with their biosimilar version of adalimumab. According to their findings, Amjevita® was associated with less injection-site pain compared with Humira®, based on pain scores given by clinical trial patients with moderate to severe rheumatoid arthritis. They found that pain site scores (based on a 100-mm visual analogue scale) were significantly lower at each 4-week office visit for the biosimilar.

The researchers theorize that the reason for the benefit may be the different excipients used in the biosimilar versus the originator drug.

The Coming Adalimumab Biosimilar Pricing Free-for-All

The dam wall will be broken when AbbVie’s patents on Humira® are invalidated or expired, or perhaps litigation is settled. This may happen in 2018, 2020, 2022—it is really anyone’s guess, but the one thing that is known for sure is that the day after this occurs, a quite sudden experiment in intensive competition will be underway.

There will be anywhere from 3 to 5 adalimumab biosimilars approved by the FDA when the patent fight is done. Unlike in the Hatch-Waxman Act, where there is an exclusivity period for the first generic market entrant, the BPCIA does not grant a similar benefit for the first-to-market biosimilars. And by the year 2018 or 2020, most expect the 180-day notification period to either be nullified by the Supreme Court or by Congressional legislation. In other words, there will be little restraint on competition.

THE ADALIMUMAB BIOSIMILAR PIPELINE 
Manufacturer Product Comments
Amgen
Amjevita™ (adalimumab-atto)
Approved by the FDA in September 2016
Amgen believes launch in 2017 is unlikely due to patent issues
Boehringer Ingelheim
BI 695501
Filed for approval with FDA and EMA in January 2017; approval decision in Q4 2017
Sandoz
GP2017
FDA application delayed from Q4 2016 due to manufacturing capacity issues
Pfizer
PF-0641023
Phase 3 trial’s top line results reported, FDA application expected in 2017
Coherus Bioscience
CHS-1420
Phase 3 trial’s top line results reported, FDA application expected in 2017
Samsung Bioepis
SB5
Filed with EMA in July 2016
The Merck Group (EMD Serono)
MSB11022
Phase 3 trials underway for plaque psoriasis (may only target this indication)

Will AbbVie remain in what is still a highly lucrative market for a drug that has paid off its research and development investment many times over? It is likely that with all of the potential players trying to keep their heads above water during the flood of competition, pricing discounts could finally be close to the dreams of payers and other purchasers (≥ 40%). This scenario depends somewhat on whether one player gambles on an early start and markets their product before patent litigation is cleared. This launch “at risk” could alter the competitive landscape. Another possible element could be AbbVie entering into an agreement with Amgen, allowing it to launch well before the others are approved. However, AbbVie’s pronouncements to date seem to be focused on fortifying the dam wall not breaching it.

The only parallel may be the moment the 6-month generic exclusivity expires, and a gaggle of manufacturers launch their products. However, we’re on a completely different level of expenditure and potential savings here. Hopefully, the dam breaks sooner than later.

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.