Daiichi Sankyo: "Enhertu's Success Attributed to Optimization During Clinical Trials"

Keynote Speech by Kawaguchi, Enhertu R&D Leader,
at the Symposium Hosted by the Pharmaceutical-Bio Association and Pharmaceutical Society on the 22nd

The R&D leader at Daiichi Sankyo, who spearheaded the development of the antibody-drug conjugate (ADC) anti-cancer drug "Enhertu (T-DXd)," stated that the key reason for Enhertu's success was the optimization of the drug during the clinical process. He explained that utilizing the clinical process not only for "validation" but also as an additional phase of "development" led to this achievement.

Yoshinori Kawaguchi, leader of Daiichi Sankyo T-DXd, made this statement on the 22nd at the "New Drug Development Symposium" jointly hosted by the Korea Pharmaceutical and Bio-Pharma Manufacturers Association and the Korean Pharmaceutical Society at COEX Magok in Gangseo-gu, Seoul. Kawaguchi said, "In the past, ADCs had unstable drug-to-antibody ratios (DAR), which led to significant fluctuations in efficacy and safety. However, Enhertu achieved a uniform composition through precise conjugation," adding, "This stability directly translated to overwhelming efficacy."

Yoshinori Kawaguchi, the leader of Daiichi Sankyo T-DXd, is being interviewed by reporters on the 22nd at Magok, COEX, Gangseo-gu, Seoul, during the 'New Drug Development Symposium' jointly hosted by the Korea Pharmaceutical and Bio-Pharma Manufacturers Association and the Korean Pharmaceutical Society. Photo by Jung Donghoon

Daiichi Sankyo, together with AstraZeneca of the United Kingdom, succeeded in commercializing the ADC anti-cancer drug "Enhertu" at the end of 2019. Enhertu's global sales last year exceeded 5.6 trillion won. With an annual growth rate of nearly 50%, it is the most prominent global blockbuster in the ADC anti-cancer field. ADCs are called "anti-cancer guided missiles" or "magic bullets" because they minimize effects on normal tissue while maximizing cancer cell killing. In actual clinical trials, the objective response rate (ORR) was more than twice that of the previous treatment, trastuzumab emtansine (T-DM1), exceeding 60%. The objective response rate represents the percentage of patients whose tumor size decreased by a predefined amount among all patients who received cancer treatment.

When asked, "Why has Enhertu alone achieved exceptional success among so many ADCs?" Kawaguchi identified the "combination strategy" as the core competitive edge. He explained, "The efficacy and safety of ADCs are not simply the sum of the antibody and payload (drug), but are determined by integrated design, including formulation, pharmacokinetics, and clinical optimization."

At the early clinical stage, Daiichi Sankyo defined HER2 (human epidermal growth factor receptor 2) expression as a "spectrum" rather than a binary (positive or negative), and expanded indications to include patients with low expression. HER2 is overexpressed in some cancer cells, causing rapid cancer cell growth. Many ADC therapies, including Enhertu, are developed to target HER2. He explained, "When the drug is administered, it permeates adjacent tumors, resulting in a 'bystander effect' that plays a significant role in clinical outcomes." Thanks to this structural characteristic, the therapeutic area expanded to include not only patients with high HER2 expression but also those with low expression, leading to multiple indication approvals for Enhertu in the United States, the European Union, Japan, Korea, and other countries.

Yoshinori Kawaguchi, leader of Daiichi Sankyo T-DXd, is giving a lecture at the 'New Drug Development Symposium' jointly hosted by the Korea Pharmaceutical and Bio-Pharma Manufacturers Association and the Korean Pharmaceutical Society, held on the 22nd at COEX Magok in Gangseo-gu, Seoul. Photo by Jung Donghoon

Kawaguchi stated, "At Daiichi Sankyo, we view the clinical process not as 'validation' but as 'development.' This is the biggest difference from other ADCs." Daiichi Sankyo revised the formulation, dosage, and administration design more than ten times during just phase 1 clinical trials, using the clinical development itself as a process to advance ADC technology. He explained that the "complete platform operation capability," which combines the antibody expertise of the former Sankyo Pharmaceutical, the anti-cancer technology of Daiichi Pharmaceutical, and more than 40 global combination clinical trials with AstraZeneca, created today's competitive edge.

Enhertu is also expanding its connections with Korean companies. In November last year, Daiichi Sankyo signed a contract with the Korean biotech company Alteogen to develop Enhertu as a subcutaneous (SC) injectable formulation. The plan is to improve the convenience of Enhertu administration through this partnership.

After the lecture, when asked by a reporter about the possibility of collaboration with Korean companies, Kawaguchi said, "There is significant potential for collaboration not only with Alteogen but also with other Korean companies. The Korean bio industry is impressive for its rapid decision-making and investment capabilities. It has the execution power to expand business into the US and European markets." Regarding Korea's ADC technology, he added, "Platform technology capabilities are growing, and I believe Korean companies are fully capable of being partners in actual clinical stages."

This content was produced with the assistance of AI translation services.