Over the last several months, there's been a flurry of activity surrounding the development of biosimilars. Basaglar—a biosimilar version of Sanofi’s blockbuster Lantus (insulin glargine) manufactured by Eli Lilly and Boehringer Ingelheim—received tentative approval from the FDA in August; the FDA made progress towards defining a regulatory pathway for biosimilars with the 351(k) pathway, which outlines submission criteria; and Sandoz became the first company to file under the 351(k) pathway when it submitted its application for Zarzio, the biosimilar versoin of Amgen’s Neupogen (filgrastim) to prevent infection and bolster immune function in chemotherapy-treated patients.
On the other side of the Atlantic, the EU continued to rack up biosimilar approvals—18 as of this past June. And of course, there’s India, which also has a fairly well-developed approval pathway for biosimilars. To cite just one example, in September, a biosimilar version of Remicade (infliximab) developed by U.S.-based Epirus Biopharmaceuticals was approved by the FDA in India. It will be marketed as Inflimab, manufactured in Mumbai by Reliance Life Sciences, and distributed by Ranbaxy Labs.
Follow-on biologics in China
It seems that the entire world is working towards a framework for developing and approving biosimilars, as demand grows for access to biologics at lower prices. But what about China—a $75 billion pharmaceutical market (ranked 3rd after the U.S. and Japan)—that is growing at a compounded annual rate of 25%?
China, too, is embracing biosimilars, with three approved products being sold in the Chinese market and several high-profile Chinese biotech companies building GMP-certified manufacturing facilities for biosimilar production.
But there's a twist. In China, there is no formal set of regulatory guidelines around the approval or manufacturing of biosimilars. In fact, with respect to regulatory overisight, biosimilars are treated more like novel biologics. That's what's led some industry experts like Greg Scott, founder and president of consulting firm ChinaBio LLC, to suggest that the copycat biologics that are approved in China aren't biosimilars at all—they're follow-on biologics.
Biosimilars vs follow-on biologics
While almost everyone uses the terms “biosimilar” and “follow on biologic” interchangeably, strictly speaking, biosimilarity is a more rigorous standard. In the U.S. and Europe, a copycat biologic product must have the same amino acid sequence as the originator product to be defined as a biosimilar. It must also possess the same glycosolation patterns, and other structural features. Biosimilars don't have to be exactly the same as their originators, but the do have to be very close in terms of efficacy and safety.
But since China lacks a formalized pathway for biologics, manufacturers in the country have far more latitude in designing them. Technically speaking, a follow-on biologic product can be approved in China even if it doesn’t have the exact same recombinant DNA sequence.
Another problem is that current Chinese follow-on biologics are manufactured in non-GMP certified facilities, which disqualifies the products from being sold in the U.S. and EU. As a result, their overall quality tends to be lower than the originator product, with varying degrees of biologic activity. But as the middle class grows in China and more Western-educated individuals return, the demand for biologics continues to grow.
Leading the way
The “biosimilar” version of Enbrel (etanercept) is marketed as Yisaipu in China and manufactured by Shanghai CP Guojian (CPG). Like Enbrel, Yisaipu is used to treat rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, and ankylosing spondylitis; however, it is sold at a 40% discount compared with the originator product in China. Shanghai Celgen Biopharmaceutical Company also manufactures a “biosimilar” version of etanercept called Qiangke. In addition, CPG manufactures and sells a “biosimilar” version of Zenopax (daclizumab) under the name Xenopax, which is used to prevent organ rejection after kidney transplantation. Until 2009, Zenopax was marketed by Roche, but the company chose to discontinue distribution in the U.S. and the EU as demand faltered.
Each of the 31 provinces in China has the authority to make pricing decisions for drugs, but regardless of how follow-on biologics are priced, they are bound to be at least 25% cheaper than originator products. Within the last several years, there has been a push in China to invest in biologics manufacturing facilities (with financing from venture capitalists) and to develop a pool of life science professionals who are knowledgeable about the development and manufacturing of both novel biologics and biosimilars. Two companies in particular—Henlius Biotech Company in Shanghai and Innovent Biologics in nearby Jiangsu—are leading the way.
According to article posted on Innovent's site in August, “Innovent Biologics intends to be China’s first manufacturer of 'high-end' biological and the firm is already on its way to that vision.” Citing its commitment to meeting the rigorous approval standards of the FDA and the EMA, as well as its well-placed allies and million square-foot manufacturing facility, Innovent is confident in its ability to develop approvable biosimilars. It’s just a matter of time before it carries through—and before other companies follow suit.