The U.S. Food and Drug Administration (FDA) has disclosed the Complete Response Letter (CRL) issued for the combination therapy of rivoceranib and camrelizumab, jointly developed by HLB and Jiangsu Hengrui, for the treatment of metastatic liver cancer. The release has heightened scrutiny over the timing of potential approval.

According to the FDA website, the CRL was sent on March 20 to Elevar Therapeutics, HLB’s U.S. subsidiary, and to Jiangsu Hengrui Pharmaceuticals. The FDA clarified that rivoceranib cannot be approved as a monotherapy, noting its safety and efficacy were demonstrated only in combination with camrelizumab (investigational name SHR-1210).

The agency also cited deficiencies at Hengrui’s camrelizumab manufacturing facility in a Form 483, requiring corrective action within a year before resubmission. A Form 483 is issued when the FDA identifies manufacturing quality control concerns at facilities tied to an application. Responsibility now rests primarily with Hengrui to resolve these issues.

The approval timeline depends on three factors: the scope of additional data requested, the timing of resubmission, and whether the review is classified as Class 1 or Class 2. HLB reported via its blog that the FDA requested either three or six months of stability data. Hengrui has already secured three months. If accepted, resubmission could occur as early as September; if six months are required, filing would be pushed to December.

A Class 1 review, limited to documentation, would take three months, while a Class 2 review involving inspections would take six. This means approval could come by year-end under the most favorable scenario—or be delayed until the second half of next year if more data and inspections are required.

An HLB official noted, “Communication with Hengrui on resubmission is going smoothly, and three months of stability data have been secured. Even if six months are needed, it is only a short delay. However, given potential variables, it is difficult to predict a specific approval timeline.”

At its August 27 shareholder meeting, HLB disclosed details of its Type-A meeting with the FDA. The company stated that most issues raised in the CRL have been resolved, leaving only one minor matter. Hengrui is preparing the most complete stability dataset possible, with all other resubmission documents ready.

When asked about review classification, the company emphasized preparation over prediction: “Rather than speculating whether it will be Class 1 or Class 2, it is more important to ensure no further CRL is issued. Our focus has shifted from ‘fast approval’ to ‘certain approval.’”

Meanwhile, HLB has postponed its planned European Medicines Agency (EMA) filing from July to September, aligning it with completion of Hengrui’s dedicated camrelizumab plant. Following the FDA’s CRL, the company intends to proceed with the EMA submission only after ensuring the U.S. approval process is fully addressed.