Pharmaceuticals - Many biologic drug developers can be pleased with how well their products have performed in the market place. Blockbuster products such as Abbvie's (ex-Abbott) Humira (adalimumab) and Roche's Mabthera/Rituxan (rituximab) are examples of the success biologic products have experienced over the past ten years. Both of these products, as well as many others such as Remicade (infliximab), Herceptin (trastuzimab) and Enbrel (etanercept), are expected to continue to be multibillion dollar products for years to come.

This bodes well for API manufactures of biologic products such as Lonza and Boehringer Ingelheim. Lonza currently manufactures commercial quantities of both rituximab and adalimumab for the innovator companies at their Portsmouth, New Hampshire and Porrino, Spain sites, respectively. But follow-on versions of these products, known as biosimilars, could diminish revenues for both the marketer and manufacturer.

Europe continues to lead the way for biosimilar competition, and this doesn't appear to be changing anytime soon. Multiple biosimilar products have been competing in the EU for over five years, establishing a market that is still growing. Most recently, Korea's Celltrion submitted an application for a biosimilar infliximab product, the first MAb biosimilar application to be received in the EU. Even more MAb competition could be expected from companies such as Sandoz (Novartis) as early as the end of 2013.

Competition-free U.S. Market

In the U.S., biosimilar competition has yet to commence. The Biologic Price Competition and Innovation Act (2010) created an abbreviated approval pathway for biologic drugs that are proven to be highly similar to products already on the market. This framework has created a lot of buzz in the pharmaceutical industry, but it is still uncertain exactly how big of an impact biosimilars will have on the U.S. biologics market. Nonetheless, innovator companies are not taking any chances and are bracing themselves for competition.

Roche's rituximab may be the first monoclonal antibody (MAb) with multiple biosimilars in the U.S. market. Currently, Sandoz and Boehringer Ingelheim are both in late stage trials with a rituximab biosimilar, while Celltrion and Pfizer are in the lab with their own candidates. Both Teva and Samsung continue to stay in holding patterns with their respective rituximab products, leaving some to question if manufacturing similar versions of the MAb are too difficult.

One Step Ahead

However Roche isn't waiting around to see if development of rituximab biosimilars will indeed prove too challenging for potential players. The company has already partnered with Emcure for the development and commercialization of rituximab and trastuzumab for the Indian market, a situation similar to an authorized generic. Versions of the products will be sold by both companies, but under different brand names, offering an inexpensive option and increasing patient access across the developing economy.

But that's just the tip of the iceberg for Roche's defense against biosimilars. Roche's clinical development program for obinutuzumab, the Swiss-based company's glycoengineered type 2 anti-CD20 MAb, is designed to show superiority to rituximab in both non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL). If proven to be safer and more potent, biosimilar versions of rituximab could be competing over a smaller pie than originally hoped, with physicians more likely to prescribe the better therapy to new patients.

Expanding the Scope

Roche and Chicago-based Abbvie both continue to gain approval for new indications for their blockbuster products. Expanding the scope of indications for a biologic presents an opportunity to generate additional revue and soften the impact of biosimilar competition.

Currently, rituximab is approved for rheumatoid arthritis (RA), CLL, NHL and most recently granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Adalimumab received FDA approval for the treatment of adult patients with moderate to severe ulcerative colitis (UC) in September of 2012, its seventh approved indication in the U.S.. In addition to UC, adalimumab is approved for moderate to severe RA, moderate to severe polyarticular juvenile idiopathic arthritis (JIA), psoriatic arthritis (PsA), ankylosing spondylitis (AS) and moderate to severe Crohn's disease (CD).

Legal Options to Eliminate Competition

In addition to increasing indication approvals, Abbvie is pursuing legal options to brace for, or even eliminate, biosimilar competition for adalimumab. In March, Abbvie filed a request for injunction to prevent the EMA from allowing access to adalimumab data. This move follows the citizen petition Abbott filed in the U.S. with the FDA in April of 2012 regarding the protection of analytical, preclinical and manufacturing data used to support adalimumab's BLA application. Both efforts aim to limit companies rights to use information for competition, which could not only have a major impact on adalimumab biosimilar hopefuls, Boehringer Ingelheim and AET Biotech/BioXpress Therapeutics, but also on developers of biosimilars overall.

Meanwhile, Amgen, the manufacturer of multiple biologics including etanercept, has decided to embrace competition by investing in its own biosimilar programs. In late 2011, Amgen teamed up with Watson (now Actavis) to develop biosimilars, although the California- based company had been preparing to develop similar versions of biologic products prior to the announcement. This past February, Amgen offered more insight into their biosimilar plans. The company plans to launch biosimilar versions of top selling biologic products, including rituximab and adalimumab, starting in 2017.

Moves have already been made by Amgen for the development of a biosimilar trastuzumab product. Netherlands-based Synthon and Actavis came to terms on a global licensing agreement for the Dutch firm's trastuzumab biosimilar. The deal grants Actavis and its biosimilar partner Amgen global rights to the marketing and manufacturing of Synthon's product. The companies will work together to transition the development of the trastuzumab biosimilar to Actavis/Amgen for worldwide development and Phase 3 clinical trials.

If Amgen's move into biosimilars can help the company back-fill revenue gaps created by competition from biosimilar versions of their own products, perhaps companies like Abbvie will follow suit. Regardless, until the biosimilars market in the U.S. becomes more established, it is far more likely innovators will stick to protecting what they already have instead of investing in the unknown.