HONG KONG – China has seen a busy month of drug approvals, from Lenvima (lenvatinib, Eisai Co. Ltd. and Merck & Co. Inc.) on Sept. 5 to Elunate (fruquintinib, Hutchison China Meditech Ltd.) and Soliris (eculizumab, Alexion Pharmaceuticals Inc.) on Sept. 6. More notably, the three drugs, all accepted under the priority review pathway, were granted marketing approval in about a year.
The NDA for Lenvima was filed in October 2017, while those for Elunate and Soliris were submitted in June 2017.
According to the U.K.-based Centre for Innovation in Regulatory Science, in 2013 the median NDA approval time for multinational company products in China was 600 days. Under new policies, China is fervently working to introduce new drugs to the country.
This summer, China also gave the nod to four more foreign drugs – PARP inhibitor Lynparza (olaparib, Astrazeneca plc), two PD-1 inhibitors Opdivo (nivolumab, Bristol-Myers Squibb Co.) and Keytruda (pembrolizumab, Merck & Co.), as well as ALK inhibitor Alecensa (alectinib, Roche Holding AG).
Lynparza is China's first approved drug to be used as a maintenance therapy for treating platinum-sensitive recurrent ovarian cancer. From marketing application to approval, it took just nine months and, while still trailing approvals in other regions, the gap was much narrower. Lynparza was approved in the EU in May, in Japan in January, and in the U.S. in August 2017.
Meanwhile, Opdivo, Keytruda and Alecensa were given the green light in June, July and August this year, respectively. Keytruda got its China approval in five months, while Alecensa's came just eight months after EMA approval and nine months after FDA approval.
Chinese patients used to face severe drug lag. A new drug would typically only be available on the Chinese market five to seven years after it appeared in the U.S. or Europe.
One extreme example is Glaxosmithkline plc's Cervarix vaccine against the human papillomavirus, which was approved in China only in 2016, a decade after it was given the green light in the U.S. (See BioWorld Today, July 19, 2016.)
New policy regime
The approval of those latest drugs shows that the situation is quickly changing.
"China's Center for Drug Evaluation (CDE) completed 9,680 drug filings in 2017, slashing the backlog of filings to 4,000 from a high of 22,000 in September 2015," according to a report by health care consultant Pacific Bridge Medical.
Helen Chen, managing director and head of China and Asia Life Sciences at L.E.K. Consulting, told BioWorld Asia the "basis of all the current expedited approvals is the priority review policy announced in early 2016."
"This policy covered drugs with significant clinical value, such as the new ones with innovative treatments. It also covered drugs for treating specific diseases such as hepatitis and cancer, generics, especially those that are the first, and drugs in short supply that matter to public health," Chen added.
Between 2001 and 2016, China approved just over 100 new drugs, whereas developed countries approved 433.
As of May 2017, 19 drugs were granted marketing approval via the priority review pathway. Imported drugs accounted for 63 percent of the total. One prominent example is Astrazeneca's lung cancer drug, Tagrisso (osimertinib), which obtained its approval in 21 days.
Besides the priority review pathway, Chen said there are also newer policy directives that aim to support China's goal of having international product approvals as close to their home country approvals as possible.
One of those directives is the acceptance of overseas clinical data, which was announced by China in October last year. Before that, companies had to conduct full phase III trials in China to demonstrate the drug’s efficacy in mainland Chinese. Now, they can discuss with CDE to only provide data that show lack of ethnic differences.
Lynparza became the first overseas drug to be sanctioned under China's new priority review policy on the basis of international multicenter data, according to market intelligence provider Globaldata.
Another noteworthy move was China joining the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). ICH requires a nation's drug approval agency to adhere to international standards and guidelines.
“China is now adopting ICH. By definition, this closer aligns China’s clinical trial environment to international norms and allows MNCs to better perform trials in China. This also supports Chinese companies for international submission,” said Justin Wang, partner at L.E.K.
Other policies include encouraging earlier clinical trials by giving approval by default after 60 days since an application is filed and committing to specific response dates and consultations.
"The package of reforms is designed to encourage manufacturers to bring their best products to the market in China before or simultaneously with launch in other markets," Nick Beckett, co-head of the CMS Life Sciences & Healthcare Group, told BioWorld Asia.
Changing local landscape
"In time, the new policies are likely to benefit foreign manufacturers of imported drugs in many therapeutic areas," said Beckett. Such benefits could be lower costs of conducting clinical trials in China and the significantly shorter registration timelines.
Chen agreed. "International biopharmas that would not previously consider China due to the long timelines and lower pricing are now relooking at the market and exploring whether they should enter China," said Chen.
The faster arrival of imported drugs is also pushing domestic players to step up their game in innovation.
For example, the approval of Lynparza has stirred up competition in the market targeting ovarian cancer. Chinese firm Beigene Ltd. is developing the investigational PARP inhibitor pamiparib to treat gastric and ovarian cancers. U.S. firm Tesaro Inc., meanwhile, is working with Chinese partner Zai Lab Ltd. on PARP inhibitor Zejula (niraparib), recently initiating a phase III trial in China looking at Zejula as first-line maintenance for platinum-sensitive ovarian cancer. Tesaro and Zai aim to combine results of the domestic clinical trial with those from foreign trials to submit for regulatory approval, which could come by 2020.
Chen also said the friendly regulatory policies have stimulated drug innovation originating in China.
"This is also exciting for the biopharma startups in China. We are aware that a number of returnee-founded startups have chosen to do early clinicals outside of China," she said.