The world’s first CAR-T therapy for solid tumors has passed muster in China, with the country's National Medical Products Administration (NMPA) giving the green light to CARsgen Therapeutics’ satricabtagene autoleucel (satri-cel) in its flagship global approval.
Satri-cel is indicated in patients in China with Claudin18.2-positive, HER2-negative advanced gastric/gastroesophageal junction adenocarcinoma who have failed at least two prior lines of therapy. To its knowledge, CARsgen is “the first in the world to successfully identify, validate, and report the solid tumor-associated antigen Claudin18.2 as a valid target for CAR T-cell therapy,” it said in a June 22 press release. Expression of Claudin18.2, described by the company as a "highly selective" marker protein, is limited in healthy tissues and conversely is "highly expressed" in gastric cancer and other tumor types, according to CARsgen.
In trials, satri-cel showed “significant efficacy benefit and a good safety profile” over existing treatments, CARsgen said Monday.
A phase 2 study in late 2024 had the company racing to submit its milestone drug for approval with Chinese regulators after the trial met its primary progression-free survival endpoint. The study compared satri-cel to a physician’s treatment choice of several chemotherapies.
The CAR-T was specifically linked to a median progression-free survival of 3.25 months over 1.77 months in the physician’s choice arm, with median overall survival landing at 7.92 months versus 5.49 months, respectively, CARSgen revealed at last year’s American Society of Clinical Oncology (ASCO) Annual meeting.
Solid tumors mark an area where CAR-T therapies have long struggled to break through to approval, making CARSgen's nod an important milestone for the class write large. To go along with its treatment, the company also created a preconditioning regimen that involves low-dose nab-paclitaxel chemotherapy along with traditional lymphodepletion chemo, CARSgen explained.
Gastric cancer holds a high disease burden, especially in Asia, where more than 70% of new and fatal cases occur. Chinese patients specifically account for some 47% of the global gastric cancer burden, CARsgen pointed out.
“As the world's first successfully marketed CAR-T therapy for solid tumors, satri-cel not only fills the gap in later-line treatment for advanced gastric cancer but also ushers in a new era of cellular therapy for solid tumors,” professor Lin Shen, M.D., whose team at Peking University Cancer Hospital led the drug’s clinical studies, commented in the release. “This breakthrough lays a critical foundation for advancing frontline therapy and combination treatment strategies, and is expected to reshape the treatment landscape of gastric cancer and even gastrointestinal tumors.”
CARSgen is “actively expanding” its satri-cel application into early-line and perioperative treatment regimens, it said. A phase 1 study in pancreatic cancer is ongoing in China, among others.
“We will go all out to advance the clinical application and market access of satri-cel, ensuring that this innovative therapy benefits Chinese patients widely and in a timely manner,” the company’s founder, CEO and chief scientific officer Zonghai Li, M.D., Ph.D., added. “At the same time, we will strive to expand this product to more countries and regions to meet greater medical needs.”
Satri-cel is one of a handful of drug applications the NMPA signed off on on Monday.
3 other first-in-class approvals
In addition to Carsgen's CAR-T, Chinese authorities also granted three other world-first approvals.
The NMPA has greenlighted the world's first bispecific antibody-drug conjugate in Sichuan Biokin Pharmaceutical's EGFRxHER3 ADC izalontamab brengitecan (iza-bren) as a new treatment option for nasopharyngeal carcinoma, a rare type of head and neck cancer. By paying Biokin's subsidiary SystImmune $800 million upfront as part of a potential $8.4 billion deal, Bristol Myers Squibb holds the drug's ex-China rights. The conditional approval now allows the infusion to treat Chinese patients who have failed on at least two lines of prior systemic therapies, including a PD-1/L1 inhibitor and chemotherapy.
Outside of China, BMS is testing iza-bren in global phase 2/3 tests in previously treated triple-negative breast cancer, bladder cancer and EGFR-mutated non-small cell lung cancer.
In another first-in-class nod, the NMPA cleared a novel antibacterial spray by Pulai Pharmaceutical to treat wound infections or superficial burns caused by infection-causing bacteria Staphylococcus epidermidis, Staphylococcus haemolyticus, and Acinetobacter baumannii, which have been linked to multi-drug resistance in hospitals.
The therapy's active ingredient is a novel non-antibiotic called peceleganan. It represents a new class of antimicrobial peptide, which acts through electrostatic interactions and hydrophobic insertion to disrupt bacterial cell membranes, effectively treating skin wound infections without relying on traditional antibiotic mechanisms.
The drug is commercially partnered with Sino Biopharm's Chia Tai Tianqing Pharmaceutical.
Also in infectious diseases, China's Genrix Bio won approval for its silevimig, the world's first bispecific antibody for post-exposure prophylaxis against rabies. The bispecific antibody targets dual epitopes of the rabies virus for passive immunization following suspected exposure to rabies, a “substantial” but under-penetrated market, China Medical System, which holds commercialization rights to the drug, said in a release. The drug contains a small dose that can be manufactured at scale and allows for easier administration, the company pointed out.
Meanwhile, Eli Lilly also nabbed a Chinese approval for its Inluriyo in ER-positive, HER2-negative, ESR1-mutant locally advanced or metastatic breast cancer patients who have previously received endocrine therapy. The drug, an oral selective estrogen receptor degrader (SERD), first won FDA approval in September after cutting the risk of progression or death in eligible patients by 38% versus standard endocrine therapy, marking the agency’s second nod for an oral SERD.
In the U.S., Inluriyo is only sold as a monotherapy as data proving its benefits in combination with Lilly’s CDK4/6 inhibitor Verzenio (abemaciclib) were less mature at the time. However, Lilly later confirmed a favorable overall survival trend for the combo and China’s drug regulators in turn have approved the Inluriyo-Verzenio combo along with its monotherapy indication.