Jinyangon "Aimed for a Home Run but Hit a Double... Collaborating with Hangseojeyak for Final Approval"

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"I tried to hit a home run, but I would appreciate it if you could understand it as having reached about a double. We can say that the overall efficacy issue has been passed over, and I hope you encourage the employees for their devastation."

Jinyangon, Chairman of HLB, attending an emergency press conference held on the 17th in Gangnam-gu, Seoul
[Photo by Lee Chunhee]

Jin Yang-gon, chairman of HLB, said at an emergency press conference held on the afternoon of the 17th in Gangnam-gu, Seoul, "I cannot express the devastation of my feelings in words," adding, "Since it is not over yet, we will cooperate with Hansoh Pharmaceutical so that such results come out, as 92% of new drugs that received a Complete Response Letter (CRL) have been finally approved."

On the morning of the same day, HLB received a CRL for the anticancer new drug rivoceranib, which was aiming for approval from the U.S. Food and Drug Administration (FDA) as the first domestic biotech company. A CRL is a letter sent by the FDA when additional inspection or data supplementation is required for an item whose approval application has been received. The company that receives it must revise and supplement the relevant matters and reapply for approval. However, neither HLB nor Hansoh Pharmaceutical, which developed camrelizumab, the drug for combination therapy, clearly understands the details related to the CRL, so it may take considerable time even to reapply for approval. In this case, approval within the year may also become uncertain.

The FDA pointed out two major issues through the CRL: the drug manufacturing process and the delay in inspection of the medical institutions conducting clinical trials. First, the manufacturing-related issue was related to the Chemistry, Manufacturing, and Controls (CMC) of camrelizumab production. However, Chairman Jin explained, "Hansoh Pharmaceutical has not been notified by the FDA of any defects." Hansoh Pharmaceutical currently produces both camrelizumab and rivoceranib, and there were no CMC-related issues for rivoceranib.

The issue presumed to have been pointed out by the FDA was found during the FDA’s inspection of camrelizumab production in January. The fact that a problem was found was also notified to HLB at that time. However, since they are partners rather than a subsidiary relationship, Hansoh Pharmaceutical does not share all related matters with HLB. Chairman Jin said, "Hansoh Pharmaceutical is confident that it has sufficiently explained and proven the issues pointed out by the FDA," but added, "As far as I know, Hansoh Pharmaceutical has never received a response from the FDA saying there are no problems." He continued, "Since there was no feedback at all, Hansoh Pharmaceutical probably thought the issue was resolved and was naturally taken aback. Since Hansoh Pharmaceutical is also under urgent pressure, they will hurry to resolve the problem."

Regarding the other issue, the inspection of medical institutions conducting clinical trials, the Bioresearch Monitoring Program (BIMO) investigation, Chairman Jin emphasized, "To be precise, it is a delay issue and a completely different problem from the CRL."

The combination therapy of rivoceranib and camrelizumab demonstrated efficacy and safety through a Phase 3 clinical trial conducted from 2019 to 2022 involving 543 patients at 121 medical institutions in 13 countries. However, the FDA mentioned in this CRL that there were regions where BIMO could not be conducted due to travel restrictions during the review process. Due to the mention of 'travel restrictions,' HLB views Russia's invasion of Ukraine as the cause. Because of the war, inspections of Russia (13 sites) and Ukraine (8 sites) became difficult, and since the racial composition of this clinical trial was heavily weighted toward Asians at 83%, those institutions were selected as 'key institutions,' and inspection of them was deemed essential, according to analysis.

Chairman Jin said, "You need to know why they want to go there," but drew a line by saying the issue is unlikely to be due to racial composition. He emphasized, "The FDA has never raised issues regarding racial composition," adding, "We said we would diversify through post-marketing surveys to include Hispanics, Blacks, etc., and the FDA did not provide any opinions on this either."

While HLB has emphasized that there were 'no problems' during this approval process, the company responded to the sudden CRL by calling it an 'unexpected problem.' Chairman Jin explained, "Opinions in the new drug approval sector can be heard through review, but CMC and approval by the FDA are independent and do not communicate with each other," adding, "The opinions of FDA-experienced employees within the company were that, assuming there are no problems with CMC, there would be no major obstacles to approval." Regarding the incomplete BIMO, it was confirmed that the FDA had mentioned it during the approval process. However, Chairman Jin said, "I saw it as a conventional phrase," emphasizing, "The largest hospitals completed BIMO, so it is not that BIMO was not done at all, and they did not specify to us which regions they wanted to inspect but could not. Therefore, this is not a core issue."

Han Yonghae, CTO of HLB Group, Jin Yanggon, Chairman of HLB, and Jung Seho, CEO of Elevate Therapeutics, attending an emergency press conference held on the 17th in Gangnam-gu, Seoul (from left)
Photo by Lee Chunhee

HLB and Hansoh Pharmaceutical stated that they will first quickly identify the problems to resolve them. Chairman Jin said, "For CMC, we just need to supplement the parts that the FDA raised issues with," and "For BIMO, we need to continue discussions, such as asking for specific proposals on where to substitute." Since it is still unclear which parts need supplementation, the company refrained from commenting on the specific timing of reapplication or approval at the press conference.

Finally, Chairman Jin said, "We tried to hit a home run with the grand dream of obtaining global approval for the combination therapy," adding, "People ask if it is a problem when a CRL comes out, but there is no serious efficacy issue, right? Frankly, it is unfortunate, but it seems we reached at least a double." He continued, "92% of new drugs that received a CRL have been finally approved," and said, "We will cooperate with Hansoh Pharmaceutical to achieve such results."