SHANGHAI – Innovent Biologics Inc., of Suzhou, has kicked off two pivotal phase III trials in China for biosimilar antibodies of global blockbusters. Innovent's IBI301 will be tested in a head-to-head trial with Rituxan/Mabthera (rituximab, Roche AG) in patients with non-Hodgkin's lymphoma and IBI303 will go up against Humira (adalimumab, Amgen Inc.) for the treatment of ankylosing spondylitis.

That will be Innovent's first foray into late-stage clinical trials and the company will be tackling two phase III trials simultaneously. It is also among the first biopharmas to test China's new biosimilar regulations passed in early 2015 which spelled out standards for comparability to originator reference drugs.

Prior to that, biologics touted as being similar to brand name blockbusters did not have to prove they were similar, instead, they went through the regulatory path as new drugs. This often meant that any discrepancies between the original and copy were not well understood.

Today, China's biosimilar rules follow U.S. and EU guidelines in some key aspects. They stipulate that biosimilars have the same amino acid sequence as the reference drug and set out a familiar pathway to show comparability via pharmacology data, nonclinical studies and clinical studies. (See BioWorld Today, Nov. 11, 2014.)

Long before the biosimilar guidelines came into effect, Innovent had been preparing for the day when it would put its biosimilar products through the rigors of a head-to-head clinical trial.

"We have been working on this for five years," Michael Yu, CEO and founder of Innovent, told BioWorld Today. "Not many people in China who are developing biosimilars are doing the head-to-head comparison yet. None of the 96 biologics approved in China are approved based on a head-to-head comparison study."

Along with other industry leaders, Yu participated in government policy discussions before the new regulations were finalized, and has been a vocal supporter of improving the quality of drugs developed in China, and for the industry in China to be more closely aligned with global rules.

"For any biological, if you want to make a copy you need to show similarity otherwise it is not fair for patients: Why should they take something worse than the drug that is available?" said Yu.

GETTING PARTICIPANTS WILL BE EASY

Innovent's two phase III trials will enroll 500 patients each. But unlike developed markets, Yu said finding so many willing participants in China will not be difficult. For various reasons related to cost and access, the market for biologics has not taken off in China the same way it has in other developed markets. He predicts patients will be keen to enroll in the trials to get access to drugs that would otherwise be hard to come by.

The real challenge will be the cost of the trial, and purchasing large quantities of the reference drug.

"The biggest challenge will be the expense. With large trials you are talking about ¥200 million or ¥300 million (US$30 million to $45 million). It used to be that Chinese companies were unwilling to do it but now it has become essential. It shows that China has increased investment in R&D and innovation," said Yu.

If IBI301 and IBI303 succeed in their head-to-head comparability trials, Innovent will have the chance to put their substantial biologic manufacturing facilities to greater use. Designed to meet FDA, EMA and cGMP standards, Innovent has two 1,000 litre bioreactors operational and plans for another four 2,000 litre bioreactors.

The market potential for biosimilars in China is sizable and growing. According to 2013 data from Citi, Rituximab was the top-selling biologic in China accounting for 34.3 percent of the monoclonal antibody market, growing at 23 percent CAGR from 2010 to 2013. But the local competition will be stiff. According to Kantar Health, products for ankylosing spondylitis markets are dominated by local products in China.

50 PERCENT PRICE REDUCTION

Pricing will be a key success factor and Yu predicted they will be able to offer a 50 percent price reduction from originator products. He is optimistic that trend will be for the government to put high-quality molecules on the Essential Drug List and offer reimbursement. At the moment, most patients pay a hefty portion of their drug costs out of pocket.

For the time being, Yu said he does not have plans to bring Innovent's biosimilars to markets outside of China unlike Taiwan's JHL Biotech Inc., which has been approved to start trials in the EU for their biosimilar of Roche's rituximab.

Yu is shying away from attempting expensive trials in the U.S. and EU and is investing instead in a line-up of innovative assets. The intention being that the biosimilar sales in China will generate revenue to fund even more cost-intensive development of new drugs.

Along with announcing the two phase III trials, Innovent also received clinical trial approval from the CFDA for IBI308, a fully human anti-PD-1 antibody for the treatment of advanced solid tumors.

In 2015, Innovent inked two ground-breaking deals with Eli Lilly and Co., of Indianapolis, to co-develop and co-commercialize six antibody drugs over 10 years, potentially bringing to Innovent $2 billion in upfront and milestone payments.