"'Lecraza (international product name Razcluse)' is said to be the first domestically produced cancer drug approved by the U.S. Food and Drug Administration (FDA), but it's hard to believe abroad. South Korea is a country well-known globally for its automobiles, smartphones, and K-pop, so it’s quite unexpected."
Jo Byeong-cheol, a professor of oncology at Yonsei University and director of the Yonsei-Unihan Lung Cancer Research Institute, is a key contributor to the success of Yuhan Corporation's oral non-small cell lung cancer treatment Lecraza.
Lung cancer is classified as small cell lung cancer if the cancer cells are small, and non-small cell lung cancer if they are larger. Non-small cell lung cancer accounts for about 80% of patients, with approximately 40% of them having mutations related to the epidermal growth factor receptor (EGFR) that are involved in the growth of lung cancer cells. Lecraza is a "targeted cancer drug" that inhibits the proliferation and growth of cancer cells by disrupting EGFR signaling. Yuhan Corporation introduced the candidate substance for Lecraza from the domestic bio company Oscotec in 2015.
Subsequently, after clinical trials, the global development and sales rights of Lecraza (excluding domestic rights) were re-exported to Janssen, a subsidiary of Johnson & Johnson (J&J), for $1.255 billion (approximately 1.8426 trillion won). Lecraza was approved by the FDA in August 2024, making it the first domestically produced cancer drug to receive the approval, in combination therapy with J&J's lung cancer treatment injection "Rebriant." Professor Jo led the Phase 1-3 clinical trials of the Lecraza-Rebriant combination therapy and also led the clinical trials of Lecraza and Rebriant individually.
Until now, the treatment agents for non-small cell lung cancer have been practically monopolized by AstraZeneca, a European pharmaceutical company widely known for its COVID-19 vaccine with "Tagrisso." However, on Jan. 7 (local time), J&J announced the results of a Phase 3 clinical trial indicating that the combination of Lecraza and Rebriant is likely to outperform Tagrisso in overall survival (OS). The J&J research team noted that "the Lecraza-Rebriant combination therapy is expected to maintain survival at least one year longer than Tagrisso." This is the first time significant results have been reported exceeding Tagrisso's OS.
In the pharmaceutical and bio industry, considering that the estimated sales of the competing drug Tagrisso were around $6.8 billion (approximately 9.9838 trillion won) last year, Lecraza is predicted to potentially become the first domestically produced new drug to achieve blockbuster status (generating over $1 billion in annual sales) in the near future.
On April 8, I met with Professor Jo at the office of DaAn Bio Therapeutics located in Yongsan, Seoul. DaAn Bio Therapeutics is a new drug research and development company founded by Professor Jo in 2020. He introduced himself as "one of the people in the world who sees the most lung cancer patients." Professor Jo sees around 170 lung cancer patients weekly. He notes that this is the extent to which it has decreased because of conflicts in the medical law. When I asked him if he was okay, as I was concerned about his health, he replied, "I'm naturally strong. I try to eat less and keep up with exercise as much as possible." The following is a question-and-answer session with Professor Jo.
The meaning of Lecraza's FDA approval, how is it perceived?
"Cancer drugs must be better than existing medications to gain approval; it isn't sufficient to have similar effects. There have been domestic new drugs approved by the FDA, including antibiotics, but there have been none that are blockbuster drugs. Approximately 2.5 million to 3 million new lung cancer patients arise globally each year, and previously, about 500,000 patients had only Tagrisso as a treatment option, so now there is an additional choice. It has a high possibility of becoming the first blockbuster domestic new drug approved as a first-line treatment for 500,000 patients and further becoming part of the global standard treatment regimen (with Rebriant)."
There seems to be an increase in various experiments with combination therapy in cancer treatment.
"The combination therapy seems almost certain to become the standard. Since the Lecraza-Rebriant combination has achieved meaningful success as the first case in the cancer drug market, there will be more attempts for better combination therapies. I believe this is a desirable direction."
Did leading the clinical trials for Lecraza and Rebriant individually help build confidence in the success potential of combination therapy?
"It was a miraculous event to undertake the clinical trials for Lecraza and Rebriant at nearly the same time. No one anticipated they would pair together. Back then, I was not a well-known doctor, and neither drug had received significant international attention. While Janssen was strong in the field of hematologic cancers, Rebriant was its first lung cancer treatment. I got the opportunity when American researchers rejected Janssen’s request for the Rebriant clinical trial. While conducting each clinical trial, I began to consider the combination therapy of Lecraza and Rebriant."
My undergraduate major was biochemistry. I think this must have been helpful in new drug research and development.
"When I entered college in 1990, there wasn't such an evident focus on medical school as there is now, and fields like engineering and pure sciences were also popular. I believe studying biochemistry helped in realizing the importance of new drug development and translational research (linking basic sciences with clinical trials). It’s crucial to have a good understanding of basic science to lead the entire process of drug development. Besides knowledge, having the mindset and attitude of a scientist is also essential."
What needs to change to accelerate innovation in domestic cancer drugs?
"Efforts to shorten regulatory timelines seem urgent. The approval time for new drugs by our Food and Drug Administration is significantly longer than the FDA. This is largely because the U.S. is much ahead of us in experience, expertise, and workforce in related fields. Additionally, there is a big difference in that there are far more Medical Doctors (MDs) in the U.S. who are involved in new drug research and development than in treating patients."
The concentration on medical school is a problem, but the attraction to specific popular majors like plastic surgery is also a significant issue.
"Because economic desires cannot be artificially controlled, it seems there is a need for the introduction of a national system to ensure that certain core fields, like military doctors, are responsible for basic research for a set period. The knowledge and experience gained through treating patients are also crucial for new drug development. However, the heavy burden on MD personnel in patient care leads to a problematic disconnect from basic science research. The top five hospitals in Korea (Seoul National University Hospital, Severance Hospital, Asan Medical Center, Samsung Medical Center, and Seoul St. Mary's Hospital) should take a more proactive stance in new drug development, but they are overwhelmed just by patient care. Given the current situation where sustaining operations becomes difficult as patient numbers decrease, creating systems to train personnel is necessary."
Could artificial intelligence (AI) technology help in developing effective cancer drugs?
"I believe that will happen in the near future. Sequence analysis of antibodies is very important in new drug development, and it could help improve the accuracy of that process to create materials with better efficacy. Clinical data will also be incorporated with AI to facilitate new drug development. As genetic data from patients and tumors accumulates in hundreds of thousands or millions, it will enable the inference of cancer occurrence probabilities based on race and blood type."
I'm curious about the research plans following Lecraza.
"My goal is to create ten FDA-approved new drugs in my lifetime. I will continue research for new drug development until I die. Even if I were to gain trillions of won without new drug research and development, I wouldn't consider that my life."
What are some habits to prevent cancer?
"As people age, the probability of cancer occurrence increases. Genetic predispositions cannot be ignored either. While aging and genetics are beyond our control, quitting or reducing alcohol and smoking is a surefire way to lower the probability of cancer occurrence. There are claims that moderate drinking is good for health, but the issue is that the definition of 'moderation' is difficult. Alcohol and smoking are classified as Group 1 carcinogens according to the consensus."