FDA approval delayed and retry…what’s 'Rivoceranib'?

HLB received a CRL request for Rivoceranib plus camrelizumab

Acquired rivoceranib from Bukwang Pharm in 2018…effective in treatments for liver cancer and stomach cancer

It has shown significant improvements in survival period…"Due to Jiangsu Hengrui Pharmaceuticals’ monitoring issue...we will cooperate and retry to get approval"

HLB’s rivoceranib, which was expected to be an FDA-approved new drug candidate, failed to receive final approval.

 

Although HLB confirmed that Rivoceranib combined with immunotherapy camrelizumab extended overall survival in the first-line treatment for liver cancer, they received request for supplementary documents.

 

The current request for supplementation is not related to the drug’s effectiveness but rather to an issue concerning the monitoring of Jiangsu Hengrui Pharmaceuticals’ Chemistry, Manufacturing and Controls (CMC) process.

 

Therefore, HLB plans to cooperate and reapply for approval soon.

 

HLB announced on the 17th that they received a complete response letter (CRL) request from the US FDA regarding the application for Rivoceranib plus camrelizumab combination therapy as the first-line treatment for liver cancer.

 

HLB aims to work on the supplementary documentation and reapply for approval promptly.

 

FDA must notify the approval state within the 6 months of receiving a developer’s CRL.

 

“We cannot be certain, but there were some points during the CMC monitoring process of Jiangsu Hengrui Pharmaceuticals.

 

In response to the request, we provided supplementary documents, but it seems our reply may not have been adequate,” HLB Chairman Jin Yang-gon said.

 

“In my opinion, Jiangsu Hengrui Pharmaceuticals, which owns 17 pharmaceutical items, can solve any problem,” He added.

 

“We will closely cooperate with Jiangsu Hengrui Pharmaceuticals and will try to get FDA approval soon.

 

We will also speed up for global phase 3 clinical trials for the next indication.” Rivoceranib, acquired from Bukwang Pharm, closer to be a new FDA-approved drug Rivoceranib is an oral anticancer drug that selectively inhibits vascular endothelial growth factor receptor-2 (VEGFR2), which is involved in angiogenesis.

 

The development of Rivoceranib started after Elevar Therapeutics of the US acquired global licensing rights of the drug from Advenchen Laboratories.

 

Bukwang Pharm recognized Rivoceranib’s potential and secured licensing rights of Korea, Europe, and Japan from Elevar Therapeutics in 2009.

 

Subsequently, HLB paid KRW 40 billion to acquire Rivoceranib’s development right from Bukwang Pharm in 2018.

 

Then, HLB incorporated Elevar Therapeutics as its subsidiary and secured Rivoceranib’s global rights, excluding China.

 

HLB also acquired the substance patent of Rivoceranib and made it its asset.

 

HLB and Jiangsu Hengrui Pharmaceuticals have been developing Rivoceranib plus camrelizumab combination therapy for the treatment of liver cancer and stomach cancer.

 

Jiangsu Hengrui Pharmaceuticals’ camrelizumab inhibits PD-1 protein expressed on the surface of immune cells (T cells), preventing the binding to PD-L1 receptors on cancer cell surfaces, thereby activating immune cells.

 

HLB obtained positive results for the combination therapy in the first-line treatment of liver cancer and submitted a New Drug Application (NDA) to the FDA in May last year.

 

The approval was based on the results of the CARES-310 Phase 3 trials, disclosed at 2022 ESMO by HLB and Jiangsu Hengrui Pharmaceuticals.

 

The clinical trials compared the efficacy and safety of Rivoceranib plus camrelizumab to Bayer’s Nexabar, which is used as a standard therapy for liver cancer.

 

In clinical trials, Rivoceranib plus camrelizumab recorded a median overall survival (OS) of 22.1 months, demonstrating an improvement compared to Nexabar’s 15.4 months.

 

This result was more extended than the OS of 19.2 months recorded by Roche’s combination therapy of Tecentriq, an immunotherapy for cancer, plus Avastin, a targeted anticancer agent.

 

Furthermore, it is also extended than the OS of 16.4 months of AstraZeneca’s Imfinzi plus Imjudo combination therapy.

 

These drugs were compared with Nexabar alone.

 

Furthermore, Rivoceranib plus camrelizumab secured statistical significance, with a progression-free survival (PFS) of 5.6 months and an overall response rate (ORR) of 33.1%.

 

Currently, HLB and Jiangsu Hengrui Pharmaceuticals are also conducting clinical trials of the drug for stomach cancer, in addition to liver cancer.

 

At the 2023 ESMO of last year, Jiangsu Hengrui Pharmaceuticals disclosed the DRAGON IV Phase 3 clinical trial’s first interim results of triple combination therapy of Rivoceranib plus camrelizumab plus chemotherapy in localized, resectable stomach or gastroesophageal adenocarcinoma.

 

The clinical results have shown that the combination therapy recorded a pathophysiological complete remission rate of 18.3%, which is an improvement compared to the chemotherapy group’s 13.7%.