Penpulimab Becomes First Fully China-Originated PD-1 Inhibitor Approved by FDA

On April 23, the U.S. FDA approved the marketing of Akeso/CHIATAI TIANQING’s PD-1 monoclonal antibody, penpulimab, in combination with cisplatin or carboplatin and gemcitabine for the first-line treatment of adult patients with recurrent or metastatic non-keratinizing nasopharyngeal carcinoma (NPC). Additionally, the FDA approved penpulimab as a monotherapy for adult patients with metastatic non-keratinizing NPC who have experienced disease progression after platinum-based chemotherapy and at least one other prior regimen.

Penpulimab was approved for marketing in China in August 2021 and has currently received approval for four indications in the country: first-line treatment of locally advanced or metastatic squamous non-small cell lung cancer (NSCLC) in combination with chemotherapy; treatment of relapsed or refractory classical Hodgkin lymphoma after at least two prior lines of systemic chemotherapy; treatment of recurrent or metastatic nasopharyngeal carcinoma (NPC) that has progressed after failure of two or more prior lines of systemic therapy; and first-line treatment of recurrent or metastatic nasopharyngeal carcinoma (NPC) in combination with chemotherapy.

Penpulimab is a novel PD-1 monoclonal antibody based on the IgG1 subtype with engineered Fc region modifications. Amino acid mutations were introduced into the heavy chain Fc region using genetic engineering techniques to achieve Fc silencing, thereby eliminating its ability to bind to Fc receptors. This modification completely abrogates ADCC, ADCP, and CDC effects, significantly reducing the depletion of effector T cells. Furthermore, the Fc engineering attenuates ADCR-mediated effects and reduces IL-8 release, thereby further enhancing immunotherapeutic efficacy.

This product was independently developed by Akeso, with subsequent development and commercialization handled by Chia Tai Tianqing Akeso, a joint venture between Akeso and CHIATAI TIANQING.

According to the FDA, penpulimab has been approved in the United States for two indications, primarily based on the pivotal registration studies AK105-304 and AK105-202.

Among these, the AK105-304 study evaluated the efficacy of penpulimab-kcqx in combination with cisplatin or carboplatin and gemcitabine in patients with recurrent or metastatic non-keratinizing nasopharyngeal carcinoma. This was a randomized, double-blind, multicenter trial that enrolled 291 patients with nasopharyngeal carcinoma who had not previously received systemic chemotherapy for recurrent or metastatic disease. The primary efficacy endpoint was progression-free survival (PFS), assessed by a blinded independent review committee according to RECIST v1.1 criteria, with overall survival (OS) as the key secondary endpoint. The median PFS was 9.6 months in the penpulimab group versus 7.0 months in the placebo group. After 12 months of follow-up, 31% of patients in the penpulimab group and 11% in the placebo group were alive and progression-free. Although the OS data were immature, with only 70% of the prespecified number of deaths for the final analysis reported, no unfavorable trends were observed.

The AK105-202 study evaluated the efficacy and safety of penpulimab monotherapy in patients with metastatic nasopharyngeal carcinoma. This was an open-label, multicenter, single-arm trial that enrolled 125 patients with unresectable or metastatic non-keratinizing nasopharyngeal carcinoma who had experienced disease progression after platinum-based chemotherapy and at least one other prior therapy. The primary efficacy endpoints were objective response rate (ORR) and duration of response (DOR), assessed by an independent radiology review committee based on RECIST v1.1 criteria. The ORR was 28%, and the median DOR was not reached.

Currently, penpulimab has multiple indications under development. Notably, the marketing application for its combination with anlotinib capsules as first-line treatment for advanced hepatocellular carcinoma has been accepted by China’s National Medical Products Administration (NMPA). In addition, Phase 2 clinical trial data on its combination with chemotherapy for advanced head and neck squamous cell carcinoma are scheduled to be presented as an “oral presentation” at this year’s ASCO Annual Meeting.

Currently, three domestically produced PD-1 inhibitors have received approval from the U.S. FDA, originating from Junshi Biosciences, BeiGene, and Akeso/CHIATAI TIANQING, respectively.

On October 29, 2023, Junshi Biosciences announced that the U.S. Food and Drug Administration (FDA) had approved the Biologics License Application (BLA) for toripalimab (U.S. brand name: LOQTORZI™), an anti-PD-1 monoclonal antibody independently developed by the company. The approved indications are: toripalimab in combination with cisplatin and gemcitabine for the first-line treatment of adult patients with metastatic or recurrent, locally advanced nasopharyngeal carcinoma (NPC); and toripalimab as monotherapy for adult patients with recurrent, unresectable, or metastatic NPC who have experienced disease progression during or after prior platinum-based therapy.

Toripalimab is the first domestically produced PD-1 inhibitor approved for marketing by the PDA, and it is also the first PD-1 monoclonal antibody approved by the FDA for the treatment of nasopharyngeal carcinoma, filling a therapeutic gap for this disease in the United States. Shortly thereafter, Coherus, Junshi Biosciences’ partner, disclosed the U.S. pricing for toripalimab at $8,892.03 per vial, equivalent to approximately RMB 64,000—30 times its domestic price.

On March 15, 2024, BeiGene announced that tislelizumab, a PD-1 inhibitor independently developed by the company, had received FDA approval for the treatment of patients with unresectable, recurrent locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) who had previously undergone systemic therapy. In October 2024, BeiGene announced the official commercial launch of tislelizumab in the United States, offering this patient population a price 10% lower than that of other PD-1 therapies approved for this indication.

Tislelizumab has demonstrated outstanding performance. According to BeiGene’s 2024 financial report, global sales of tislelizumab reached $552.9 million, representing a 55% year-over-year increase, driven primarily by sales growth in China and the United States.

Currently, tislelizumab has been approved in the European Union, the United Kingdom, the United States, South Korea, Switzerland, Australia, and other countries and regions. In China, tislelizumab has received approval from the National Medical Products Administration (NMPA) for 14 indications, 11 of which have been included in the National Reimbursement Drug List (NRDL). It is currently the PD-1 inhibitor with the largest number of approved indications covered by the NRDL.

Notably, penpulimab is the third domestically produced PD-1 monoclonal antibody to receive FDA approval, and the first innovative biologic independently developed, clinically tested, manufactured, and registered by a Chinese company that has successfully obtained FDA marketing authorization. Following toripalimab, penpulimab also targets the U.S. nasopharyngeal carcinoma market, with its subsequent pricing strategy and commercial performance warranting close attention.

The internationalization of domestically produced PD-1 inhibitors is accelerating. With enhanced overseas clinical development and commercialization capabilities, Chinese innovative drugs are poised to assume a more prominent role in the global oncology treatment landscape.