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IR NEWS LETTER
IR News Letter - Angel Study Phase III Results (09/29/2019)
IR Letter (Sept. 29th, 2019) – Angel Study Phase III Results
HLB’s subsidiary, Elevar, officially announced the results of the Phase III Rivoceranib global clinical trial at the European Society for Medical Oncology (ESMO) in Barcelona, Spain on Sept. 29th.
The clinical trials were conducted on the patients, who failed 2nd or higher stomach cancer treatments, in 88 hospitals from 12 countries (US, Korea, Japan, Taiwan, UK, France, Italy, Germany, Poland, Romania, Ukraine, Russia) from February 2017 to October 2018. The subjects were 460 patients who failed standard treatment. Rivoceranib is a pill that is taken orally once daily. The test group was Rivoceranib plus Best Supportive Care and the control group was Best Supportive Care.
[Comparison of clinical trial results of gastric cancer 2nd & 3rd line treatment]
□ Rivoceranib demonstrates high efficacy
Rivoceranib's progression-free survival (PFS) was 2.83 months, higher than 2 months of Lonsurf and 1.6 months of Opdivo, licensed as a tertiary treatment for stomach cancer. The PFS results for the control group showed similar results with 1.77 months for the Rivoceranib study, 1.8 months for the Lonsurf study, and 1.5 months for the Opdivo study.
The difference in progression-free survival between the test group and the control group was 1.06 months for Rivoceranib, 0.2 months for Lonsurf, and 0.16 months for Opdivo. Proved superior efficacy.
In addition, the PFS of Cyramza monotherapy (2014), which was approved as a 2nd line treatment for gastric cancer, was 2.1 months, and the progression-free survival time between the test and control groups was 0.8 months. Clinical trials with 3rd line treatment with Rivoceranib also showed greater progression free survival compared to the 2nd line treatment with Cyramza.
The objective response rate (ORR) was Rivoceranib (6.9% vs 0%), Lonsurf (4% vs 2%) and Opdivo (11.2% vs 0%). Disease control rates (DCR) were Rivoceranib (42.4% vs 13.1%), Lonsurf (44% vs 14%) and Opdivo (40% vs 25%). Both the objective response rate and the disease control rate of Rivoceranib were statistically significant compared to the control group.
□ 5.78 months overall survival (OS), control data analysis
The overall survival of Rivoceranib was 5.78 months, higher than Lonsurf (5.7 months) and Opdivo (5.26 months).
Since there is no standard therapy for gastric cancer therapy, both Lonsurf and Opdivo trials used Best Supportive Care (BSC) as a control, as with Rivoceranib. Control group showed 3.6 months in the Lonsurf study and 4.1 months in the Opdivo study.
In the Rivoceranib study, the overall survival of the control group was 5.13 months, which is much higher than that of Lonsurf and Opdivo, and it was higher than the actual hospital data of 4.4 months based on data from the Korea Health Insurance Review & Assessment Service released in 2018. It is also higher than the control group's overall survival of 3.8 months at Cyramza’s GC 2nd line.
More encouragingly, the OS (Overall Survival) of Rivoceranib in the 4th line experimental group was 6.43 vs. 4.73(p-value = 0.0195) and PFS (progression free survival) was 3.52 vs. 1.71 (p =
In the FDA published ‘Clinical Trial Endpoints from the approval of cancer drugs and biologics (2018)’, it discussed that there is a drawback to the analysis in OS because the patients could receive additional treatments post clinical trials.
For example, Janssen's anticancer drug, Trabectedin (Yondelis), showed that the overall survival was not statistically significant, but progression-free survival was statistically significant, received the FDA new drug approval in Oct. 2015.
□ Manageable side effects, safety results analysis
The side effects of Rivoceranib have been reported to be low overall. Rivoceranib rarely develops neutropenia and leukopenia, the major side effects of cytotoxic anticancer drugs. These side effects that cause bone marrow suppression increase the risk of infection, and white blood cells are reduced, so when harmful bacteria penetrate the body, infection can progress rapidly and cause sepsis.
Serious side effects (grade 3 or higher, the higher the number of side effects) were within the manageable range of hypertension, 17.9%, amputee syndrome 2.9%, and proteinuria 7.5%, which were associated with drug effects.
This large global clinical trial once again confirmed the safety of Rivoceranib, demonstrating sufficient clinical significance compared to Lonsurf, a previously approved cytotoxic anticancer drug, as the 3rd line for stomach cancer.
□ Prove the similar efficacy without any race difference
Rivoceranib has previously been identified as having no differences in efficacy among the pharmacokinetic studies, but once again, it has demonstrated the same efficacy without racial differences in a large global clinical phase III trial, securing favorable conditions for future global licensing out.
Rivoceranib has already been proven effective in Asians with previous Phase III clinical trials and new drug approval in China, but there were doubts whether the same results would be achieved in Phase III clinical trials involving US and European patients. However, there was no difference in efficacy and adverse effects between clinical trials in Asia, the United States, and Europe.
□ Equal efficacy in patients with prior-Cyramza
Cyramza is the GC 2nd line and is the same neovascular inhibitor as Rivoceranib. Therefore, medical attention has been focused on whether Rivoceranib can be proven in patients who failed the treatment of Cyramza. By demonstrating the efficacy of the drug in patients with prior-Cyramza, we have established the basis for unlimited application of Rivoceranib reagrdless of prior Cyramza use.
□ Complete Response (CR) Cases
Two cases of complete response have been reported in Rivoceranib’s Phase III trial.
In the Phase III trial of Opdivo and Lonsurf clinical trials for the treatment of GC, there wasn’t any cases of CR. In the Phase II trial of Cyramza reported one case of CR(Complete Response)
□ GC 3rd Line Treatment
Stomach cancer has the third highest mortality rate in the world, the second most common cancer in South Korea, and the third in mortality.
Products currently approved as the 3rd line treatment for gastric cancer include Lonsurf, licensed in 17 countries including the United States (excluding Korea) in Feb. 2019, Opdivo, licensed in Japan, Korea, and Taiwan in Sept. 2017. Aitan (the same ingredient as Rivoceranib) was approved in China in Dec. 2014.