HONG KONG – With Thursday's nod for Tyvyt (sintilimab injection), a core asset of HKEX-listed Innovent Biologics Inc. to treat classical Hodgkin lymphoma, either relapsed or refractory after two or more lines of systemic chemotherapy, Chinese regulators have approved two homegrown anti-PD-1 monoclonal antibodies in little more than a week.
Innovent's approval came 10 days after the National Medical Products Administration (NMPA) cleared Shanghai Junshi Biosciences Co. Ltd.'s Tuoyi (toripalimab) for treating metastatic melanoma. (See BioWorld, Dec. 27, 2018.)
Like Junshi's Tuoyi, Tyvyt was approved for marketing in a short timeline – merely 255 days – under the priority review pathway. In Hong Kong trading on Friday, Innovent shares (HKG:1801) surged 5.2 percent on the news to close at HK$22.30 (US$2.85).
"We will manufacture and commercialize the product on our own. We have manufacturing facilities in Suzhou for that," Michael Yu, Innovent's CEO, told BioWorld.
Innovent has been preparing for this day. To support the commercialization of Tyvyt, it has a manufacturing building that houses first-stage production facilities with three 1,000-liter disposable bioreactors.
Yu added that Tyvyt will be dual-branded with Eli Lilly and Co., which co-developed the drug with the Shanghai-based biotech. The two will co-promote Tyvyt in the Chinese mainland, Hong Kong and Macau.
With proven clinical success in its home country, Tyvyt will also enter a multicenter phase Ib/II trial in the U.S., where Innovent has already obtained IND approval from the FDA.
Better and cheaper
"The efficacy and safety profile of Tyvyt is well-proven in the clinical trial," said Wang Li, senior vice president of Lilly China and head of Lilly China drug development and medical affairs.
Tyvyt has demonstrated an overall response rate of 79.2 percent and a complete response rate of 17.7 percent. It shows a safety and toxicity profile comparable to existing approved PD-1 antibodies, Merck & Co. Inc.'s Keytruda (pembrolizumab) and Bristol-Myers Squibb Co.'s Opdivo (nivolumab).
Opdivo and Keytruda were the first PD-1 antibodies to enter the China market, being approved in June and July, respectively.
Innovent, however, aims to position Tyvyt as a potential best-in-class PD-1 antibody given its biochemical and biological properties. According to the company, Tyvyt binds 10-fold and 50-fold more tightly to its target than Keytruda and Opdivo. Tyvyt also occupies more of the available PD-1 binding sites at a given drug concentration than Opdivo.
"Sintilimab demonstrated greater than 95 percent receptor occupancy for the full duration of a cycle of therapy at the 3-mg/kg dose level. In comparison, published data show that at the same 3-kg/kg dose level, nivolumab has a receptor occupancy that falls within the range of approximately 75 percent to 80 percent throughout the cycle of therapy," said Innovent.
Tyvyt could also be cheaper than Opdivo and Keytruda.
"We are finalizing our price strategy. Our product will be sold cheaper than those imported," Yu told BioWorld.
Currently, Opdivo is sold in China at ¥9,260 (US$1,348) per 100 mg, while Keytruda is priced at ¥17,918 per 100 mg.
"I think overall the prices of China-developed PD-1 antibodies will be lower than the imported ones. This will make local products more competitive as they are of high quality as well," Yu added.
Market watchers have noted that Tyvyt's capacity to stand out will come down to the biotech's commercialization capability.
"Other competitors are also expecting their NDAs soon. To win the race, you need to have a strong capability to manufacture and commercialize the product in large scale to claim the market," Hua Su, managing director of EY-Parthenon at Ernst & Young (China) Advisory Ltd., told BioWorld. (See BioWorld, Dec. 26, 2018.)
Now that Junshi and Innovent have become the first two Chinese biotech firms to market their PD-1 antibodies, Su said he believes the competition in the PD-1 therapeutic space will only get more intense as the approval timeline gets shorter.
Other local competitors include Jiangsu Hengrui Medicine Co. Ltd.'s SHR-1210 (camrelizumab), Beigene Ltd.'s BGBA-317 (tislelizumab), Cstone Pharmaceuticals Co. Ltd.'s CS-1001 and Suzhou Alphamab Co. Ltd./3D Medicines (Sichuan) Co. Ltd.'s KN-305.