Backed by positive data from two phase III studies, ABP 501 could become the first product from Amgen Inc.'s burgeoning yet close-to-the-vest biosimilars program, for which the Thousand Oaks, Calif.-based firm has anticipated five commercial launches between 2017 and 2019.

A more precise timeline – when the company plans to submit regulatory applications for that Humira biosimilar, for example – has not yet been disclosed. Humira (adalimumab), a monoclonal antibody designed to block TNF-alpha, is set to lose patent protection at the end of 2016 in the U.S.; expiration in Europe will come in 2018.

But Amgen said it believes data from the two pivotal studies should serve as the basis for global regulatory submissions. Results from the latest phase III study, disclosed after market close Tuesday, showed that ABP 501, given to patients with moderate to severe rheumatoid arthritis (RA), met the primary endpoint, demonstrating clinical equivalence when compared to Humira, as assessed by ACR20 measurements (20 percent or greater improvement in ACR assessment) at week 24. As with the first phase III, which the firm reported in October showing clinical equivalence to Humira in psoriasis patients, ABP 501's safety and immunogenicity data were comparable to Humira. (See BioWorld Today, Oct. 9, 2014.)

The trial enrolled a total of 526 patients whose disease was inadequately controlled on methotrexate, randomized to receive ABP 501 40 mg subcutaneous every two weeks or Humira 40 mg subcutaneous every two weeks. A screening period of four weeks was followed by a 22-week treatment period and a safety follow-up period through to week 26.

Success in both the RA and psoriasis studies also give Amgen a good chance for an across-the-board approval in all indications for which Humira is used, given that U.S. regulators appear inclined to favor extrapolation. During a historic meeting of the FDA's Oncologic Drugs Advisory Committee last month, members voted unanimously that Sandoz International GmbH's filgrastim biosimilar, Zarxio, should be approved for all indications of reference drug Neupogen such as nonmyeloid malignancies, marrow transplants or acute myelogenous leukemia, despite the fact that it had only been tested in healthy volunteers and breast cancer patients. (See BioWorld Today, Jan. 8, 2015.)

Humira is also approved for polyarticular juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease and ulcerative colitis. In 2014, sales of the drug totaled $12.5 billion.

That's a lucrative market more than one firm would like to enter. In addition to Amgen, several others are working on Humira biosimilars, with one of the most advanced competitors coming from Sandoz, which recently launched phase III trials.

VIEW FROM THE OTHER SIDE

With two positive trials under its belt, Amgen could be the first company to file for a Humira biosimilar. Luckily, the company has a little experience with the new biosimilars pathway in the U.S. – albeit from the other side.

It owns Neupogen, a granulocyte-colony stimulating factor (G-CSF) used to treat neutropenia, which came off patent at the end of 2013, and faces approval of the first official biosimilar – i.e., the first approved under a 351(k) biologics license application – in the form of Sandoz's Zarxio. Sandoz, the generics unit of Swiss pharma giant Novartis AG, filed for approval last year (See BioWorld Today, July 25, 2014.)

Sales of Neupogen already are taking a hit with the availability of an unofficial biosimilar – Teva Pharmaceutical Industries Ltd.'s Granix, approved under the full BLA drug pathway – which has been on the market for about a year and a half. In its earnings last month, Amgen reported that full year sales of Neupogen had declined 17 percent to total $1.16 billion.

The introduction of Zarxio stands to exact an even bigger toll on Neupogen sales. The product, which has been on the market in Europe, has more than held its own with competitors, even though European regulators have approved a total of nine filgrastim biosimilars since 2008. Zarxio, in fact, ranks No. 1 in the worldwide G-CSF market, with a roughly 30 percent share.

But the U.S. filing process has not gone entirely smoothly for Sandoz. Under the Biologic Price Competition and Innovation Act (BPCIA), by filing an application along the new 351(k) pathway, the biosimilars maker agrees to provide its complete dossier to the reference drug's sponsor, to ensure there are no patent infringement issues. Amgen filed suit in federal court, claiming that Sandoz has refused to comply with that requirement, and resolving that issue could end up delaying Zarxio's launch even if it gains approval by its May PDUFA date. (See BioWorld Today, June 29, 2011, and Oct. 31, 2014.)

In seeking regulatory approval of ABP 501 as a biosimilar, Amgen would be the one responsible for sharing data, handing over all necessary materials to Humira originator North Chicago-based Abbvie, to make sure its ABP 501, which comprises an anti-TNF-alpha monoclonal antibody with the same amino acid sequence as Humira, does not infringe on any patents that extend beyond the December 2016 expiration.

BIOSIMILARS VALUE STILL UNKNOWN

Though company execs have stressed the importance of the biosimilars program – most recently during the fourth quarter earnings call – Amgen has remained somewhat circumspect with regards to that program, at least when compared to the regular updates detailing advancements of its innovative compounds.

Besides Humira, the firm has said it is expecting data from a late-stage trial in the second half of this year for a biosimilar of cancer drug Avastin (bevacizumab, Roche AG). It also has confirmed programs for biosimilar versions of Erbitux (cetuximab, Bristol-Myers Squibb Co. and Eli Lilly and Co.), Remicade (infliximab, Johnson & Johnson) Rituxan (rituximab, Biogen Idec Inc. and Roche AG) and Herceptin (trastuzumab, Roche AG), though it's not clear where those programs are in the development process.

Another three programs remain undisclosed for now.

But five of those nine programs are expected to launch between 2017 and 2019, though with few specifics available, and with the biosimilar market still largely an unknown quantity, analysts have mostly left biosimilars out of their models for Amgen's growth.

As J.P. Morgan analyst Cory Kasimov noted in a research report earlier this year, biosimilars "represent a compelling opportunity given [Amgen's] biologics expertise . . . though the potential value is hard to triangulate at this point."

Shares of Amgen (NASDAQ:AMGN) closed Wednesday at $151.45, down 78 cents.