This feature is part of a series focused exclusively on biosimilars. To view other posts in the series, check out the spotlight page.
For much of the U.S. biopharma industry 2016 was defined by intense scrutiny on prescription drug pricing. It is fitting, then, that the year also brought a rapid acceleration in the development of biosimilars — cheaper copies of expensive biologic drugs.
Two biosimilars are already on the market in the U.S., with another two approved by the Food and Drug Administration and dozens in development. As drugmakers pour investment into biosimilar pipelines, the FDA has begun taking more steps to fill out the regulatory framework for the copycat drugs.
With so many players in the space, it's easy to lose track of who is developing what, especially when companies like Amgen are on both sides of the biosimilar fight.
There are numerous companies in the space including Allergan, Biocon, Boehringer Ingelheim, Momenta, Mylan and Pfizer that all have burgeoning biosimilar pipelines.
BioPharma Dive has put together a list of the seven notable biosimilar developers that have advanced their pipeline quickly in the U.S. (think Novartis) or pose the threat to some of the more significant biologics (think Coherus vs. Humira). Here are the companies to watch:
The Swiss pharma has been at forefront of biosimilar development in the U.S., securing approvals from the Food and Drug Administration for biosimilars of Amgen’s Neupogen (filgrastim) and Enbrel (etanercept).
Novartis’ Neupogen biosimilar, dubbed Zarxio, made history as the first biosimilar cleared by the FDA and is one of only two biosimilars currently sold in the U.S. And with approval of Erelzi, an Enbel copy, Novartis owns two of the four biosimilars currently okayed for use.
Novartis isn’t stopping there, either. The company said last summer it plans to launch five new biosimilars drugs by 2020: the aforementioned, and now approved, Erelzi, along with biosimilars of Humira (adalimumab), Neulasta (pegfilgrastim), Remicade (infliximab) and Rituxan (rituximab).
While sales of its currently marketed biosimilars don’t yet amount to much, the potential is high. Global sales of the five drugs mentioned above totaled more than $44 billion in 2015. Stealing away even a small portion of those revenue streams could make biosimilars an important part of Novartis generic portfolio.
Novartis did run into a setback last year, however. In a quarterly update, the pharma disclosed its generics unit Sandoz had received a complete response letter from the FDA tied to its Neulasta biosimilar.
2) Celltrion Inc.
Headquartered in Korea, Celltrion has a deep pipeline of biosimilar candidates. Its copy of Remicade was approved in Europe back in 2013 and became just the second biosimilar to be approved in the U.S. last April.
Under a partnership deal, Pfizer is in charge of marketing the biosimilar, named Inflectra, in the U.S. The pharma giant started shipping the drug to wholesalers in late November and currently sells it at a 15% discount to Remicade's wholesale acquisition cost.
Pfizer also had rights to commercialize Celltrion’s biosimilar candidates referencing the breast cancer drug Herceptin (trastuzumab) and Rituxan, but handed them back after acquiring Hospira in 2015. The big pharma has eight biosimilars of its own in development, as of Nov. 1, including copies of Humira, Rituxan, Herceptin and Avastin.
In October, Celltrion struck up a partnership with generics giant Teva to sell the two biosimilars in the U.S. and Canada, if approved.
Amgen is on both sides of biosimilar development. On one hand, it has won FDA approval for the first biosimilar version of AbbVie’s Humira and recently submitted an application for its copy of Roche’s Avastin (bevacizumab), co-developed with Allergan.
Yet, at the same time, it is working hard to defend its biologics-heavy portfolio from encroaching biosimilars developed by other drugmakers. Global sales of Enbrel, Neulasta and Neupogen combined to account for over half of Amgen’s revenues in the third quarter last year. All three are under biosimilar threat from either already approved biosimilars or biosimilar candidates in the pipeline.
Amgen is also entangled in a high-profile legal case with Sandoz, the generics arm of Novartis, over how soon a biosimilar can be marketed after FDA approval. Sandoz had argued that it should be allowed to give Amgen its mandated 180-days notice of marketing ahead of a potential approval.
An appeals court ruled in favor of Amgen, but Sandoz appealed and that case is set to head to the Supreme Court this year.
While a nuts-and-bolts issue, the case takes on more importance as it will help shape legal precedent for the still nascent biosimilars field in the U.S.
4) Samsung Bioepis
Another Korean company, Samsung Bioepis is joint owned by Samsung Biologics and Biogen. In short order, Bioepis has advanced its first cohort of biosimilar candidates to regulators and markets.
Its Enbrel biosimilar has won approval in the European Union (as Benepali), Canada and Korea (as Brenzys), while its Remicade copy is okayed for use in the EU and Korea.
Other candidates, including biosimilars of Herceptin and Humira, have been accepted for review by the European Medicines Agency.
Bioepis has pursued a similar strategy to its Korean rival Celltrion, inking partnerships with big pharma companies to handle commercialization and marketing. In Bioepis’ case, it works with both Biogen and Merck & Co.
Merck has rights to market Bioepis’ biosimilars in the U.S., while the deal with Biogen mostly covers Europe.
Even though it hasn’t reached the US market yet, its deep pipeline and large technological base make it a player in the space.
Through its deal with Samsung Bioepis, Biogen has begun pulling in revenue from Benepali and Flixabi in the EU.
But its ties to Bioepis go deeper than just a commercialization agreement. The biotech invested around $45 million in 2012 for a 15% ownership stake in Bioepis. While its stake now sits at around 9%, Biogen has an option to purchase additional stock, up to 49.9% ownership.
To add to the interesting dynamic, Biogen also acts a contract manufacturer for Bioepis, giving it additional manufacturing capacity.
While Biogen has staked itself to biosimilar development through Bioepis, the rest of the company is in some flux. Longtime chief George Scangos has stepped down as CEO, and Biogen promoted chief commercial officer Michel Vounatsos to take his place.
The leadership shake-up follows a decision to exit the hemophilia space and spin off its drugs into a separate public company. Biogen has also been the subject of takeover speculation that, so far, has proven unfounded.
6) Merck & Co.
In some ways, Merck’s experience with biosimilar competition is a cautionary tale for other biologics makers.
Under an agreement with Johnson & Johnson, Merck markets Remicade in Europe and splits profits with J&J. In 2013 and 2014, revenue from sales of Remicade totaled roughly $2.3 billion each year. But the introduction of Celltrion’s biosimilar copy Remsima on markets in February 2015 precipitated a dramatic erosion of Merck’s Remicade revenues.
That year, revenues shrunk by over 24% (10% excluding the impact of foreign exchange) compared to the 2014. And the slide has continued. In the third quarter last year, sales added up to only $311 million — almost half the level a year prior.
But, through its partnership with Samsung Bioepis, Merck has some skin in the biosimilar game, too. The two companies collaborated on the development of MK-1293, a "follow-on biologic" to Sanofi’s Lantus.
Both the FDA and the EMA have accepted Merck’s application for approval of MK-1293, although Sanofi has claimed patent infringement. (Both Eli Lilly’s copy of Lantus and Merck’s candidate are deemed "follow-on biologics" due to the regulatory pathway under which they were submitted.)
Merck’s partnership with Bioepis also covers commercialization for biosimilars of Enbrel, Remicade (ex-EU), Humira and Herceptin.
7) Coherus BioSciences, Inc.
Coherus is one of several biosimilar makers trying to follow Amgen’s lead and win approval for a biosimilar of AbbVie’s Humira.
Coherus expects to file an application for its candidate, known as CHS-1420, sometime in the first half of 2017. In hopes of clearing a way to market, it has been attempting to invalidate several patents held by AbbVie on Humira.
Unfortunately for Coherus, the U.S. Patent Trial and Appeal Board denied the company’s request to review a key patent which concerns Humira’s formulation (U.S. Patent 9,114,116).
While a setback for Coherus’ efforts, the company believes there are other legal pathways to challenge that patent and open the door for market entry, pending approval of CHS-1420.
Coherus also recently regained the rights from Shire to a biosimilar version of etanercept, and has submitted an application for U.S. approval of a Neulasta biosimilar.