350 Years of Merck: Innovation and Focus on TGCT

Merck, a global pharmaceutical company with the vision of “Innovation” and “One for Patients,” has reaffirmed its commitment to improving patient access to innovative therapies in the Korean market.

Headquartered in Germany, Merck is the world’s oldest pharmaceutical company. It established its Korean subsidiary in 1989 and has since operated across three divisions: Biopharma, Life Science, and Electronics.

Among these, the Biopharma division represents the largest segment. Within Biopharma, the Oncology division was launched in 2005 with the introduction of Erbitux (cetuximab), a treatment for metastatic colorectal cancer. In 2021, Merck expanded its presence in the Korean oncology market with the approval and launch of Tepmetko (tepotinib), a treatment for MET mutation-positive non-small cell lung cancer. Last year, the reimbursement scope for Bavencio (avelumab) was expanded to include maintenance therapy for metastatic urothelial carcinoma, further solidifying Merck’s position in the South Korean oncology market.

At the ESMO Asia 2024 Annual Congress held on December 6 in Singapore, the results of the prospective real-world study “SPADE” were presented, garnering significant attention. The study examined the use of Bavencio as a first-line maintenance therapy for locally advanced or metastatic urothelial carcinoma in the APAC region.

In an exclusive interview with Hit News at the ESMO Asia 2024 Congress, Yariv Hefez, Senior Vice President and Head of the Global Business Franchise for Oncology at Merck, shared insights into the company’s key focus areas and efforts to enhance patient access to therapies in Korea.

“Merck’s Oncology division is committed to leading advancements in cancer treatment, focusing on revolutionizing the standard-of-care therapies for hard-to-treat cancers worldwide, including in the Asia-Pacific region.

One of the core areas of research is DNA Damage Response (DDR), where Merck is actively developing innovative therapies such as Tuvusertib, an ATR kinase inhibitor, and M9466, a next-generation PARP1 inhibitor designed to minimize toxicity compared to earlier treatments. Another key focus is on antibody-drug conjugates (ADCs), with ongoing clinical research on M9140, which targets CEACAM5. This therapy is particularly aimed at gastrointestinal cancers, including colorectal cancer, and is anticipated to complement Erbitux. Additionally, other ADC candidates are under development, though they are in the early stages and will be revealed in the future.

The division is also exploring immuno-oncology with the development of M0324, an antibody designed to address unmet needs in cancer immunotherapy. In the field of oncogenic signaling, Merck is advancing Ompenaclid, a therapy for RAS-mutated colorectal cancer. This candidate is being developed in collaboration with a U.S.-based company under an option agreement and is currently in Phase 2 clinical trials. It is being studied in combination with Bavencio and chemotherapy and holds promise as a new treatment option for patients unresponsive to Erbitux.”

“In addition to the four areas I previously mentioned, we are placing significant emphasis on fields with high unmet medical needs. One example is our recent licensing agreement for Pimicotinib, a targeted therapy for tenosynovial giant cell tumor (TGCT). TGCT is a rare tumor originating in the soft tissues of joints, synovium, and tendon sheaths, often causing severe pain and discomfort that limits patients’ mobility. Despite its impact, there has been a significant lack of treatment options, leaving a substantial medical gap.

Pimicotinib is being developed in partnership with Abbisko Therapeutics, and early Phase 3 clinical results have been highly encouraging. We plan to first launch it in China and, depending on future study outcomes, aim to expand into global markets, offering an innovative solution for TGCT patients worldwide.”

“Merck established its Korean subsidiary in 1989 and launched the Oncology division in 2005 with the introduction of Erbitux. Next year marks the 20th anniversary of Erbitux’s approval in Korea, making it a significant milestone for us.

The Oncology division is committed to providing innovative therapies to the Korean market, though the journey has not been without challenges. Korea is one of the countries with a particularly complex reimbursement process. To address this, Merck actively collaborates with the Korean government to streamline access.

Improving patient access to therapies is a priority for Merck, and personalized treatment plays a key role in this mission. Just as we have done so far, we will continue to focus on personalized medicine to address unmet medical needs. Considering our clinical plans and ongoing research in Korea, I believe all future therapies under development can be introduced here promptly.

Korea is an important market for us, as the oncology and broader pharmaceutical industries are growing rapidly. Statistics show that only about 20% of oncology drugs launched abroad receive reimbursement in Korea. However, nearly all Merck therapies introduced in Korea are approaching full reimbursement status, which reflects the significant efforts we have invested.”

“Erbitux is an EGFR-targeted therapy approved as a first-line treatment option for patients with RAS wild-type metastatic colorectal cancer, playing a crucial role in a field that had seen little advancement.

At Merck’s Oncology division, we are committed to continuously building robust real-world data (RWD) while developing innovative combination therapies to ensure Erbitux remains a valuable option in clinical practice.

One notable example is the BEACON regimen, introduced in Korea this year, which demonstrated significant overall survival benefits in patients with BRAF-mutated colorectal cancer in second-line or later treatments. Additionally, many pharmaceutical companies are focusing on combination therapies with Erbitux instead of traditional chemotherapy. Research is also underway to evaluate the efficacy of combining Erbitux with immunotherapy in the early stages of treatment. Moreover, clinical trials are investigating combination therapies targeting KRAS G12C and KRAS G12D mutations.

Moving forward, we will continue to identify new patient groups who could benefit from Erbitux, expanding its potential as a treatment option.”

“The recognition of reimbursement adequacy for Tepmetko, a treatment for MET exon 14 skipping non-small cell lung cancer (NSCLC), which accounts for only 2–3% of all patients, by the Health Insurance Review and Assessment Service’s Drug Reimbursement Evaluation Committee, is excellent news for patients in Korea.

Until now, patients with MET exon 14 skipping mutations have had limited access to effective treatments. Tepmetko demonstrated approximately twice the overall survival rate compared to traditional platinum-based chemotherapy in key clinical trials. This positions it as a therapy capable of not only extending patients’ lives but also significantly improving their quality of life.

The reimbursement process, however, was not without challenges. Merck actively engaged with the government, submitting three applications to achieve this milestone. We remain committed to close collaboration with the Korean government to reach agreements, and I am optimistic that patients will soon be able to benefit from reimbursement and access this therapy.”

“Bavencio has redefined the standard treatment paradigm for urothelial carcinoma. Prior to its introduction, chemotherapy was the mainstay of treatment, offering a median overall survival of just 12–15 months. However, with the advent of maintenance immunotherapy using Bavencio, patients now have the opportunity to survive beyond 40 months.

In the pivotal JAVELIN Bladder 100 trial, Bavencio achieved a remarkable median overall survival of 29.9 months from the initiation of chemotherapy. Furthermore, the real-world data (RWD) study AVENANCE demonstrated that patients receiving second-line ADC therapy after Bavencio maintenance therapy recorded an overall survival of 40.8 months (95% CI: 32.6–42.1) from the start of chemotherapy.

It’s also important to consider not only the tumor-specific efficacy of a treatment but also its impact on patients’ overall quality of life, toxicity, and adverse events. In this regard, Bavencio strikes an optimal balance between clinical efficacy and maintaining or improving patients’ quality of life, making it an ideal therapeutic option.”

“Many companies that once led their industries have disappeared over time. However, Merck has continued to exert its influence in the pharmaceutical industry, and I believe the key lies in our commitment to ‘Innovation.’

Founded in 1668, Merck has thrived for over 350 years through relentless innovation. The company’s greatest strength is its ability to periodically reinvent itself.

This philosophy is reflected in our logo and branding, which stand out with their vibrant and diverse colors. I see these as a representation of Merck’s dedication to innovation and its unwavering perseverance—qualities that underpin our success.”

“Absolutely. Before joining the Oncology division, I worked in the biosimilar business unit, where I had the opportunity to collaborate with Korean companies. It was a personally very positive experience.

The Koreans I worked with were passionate, innovative, and intelligent, and they possessed capabilities spanning both clinical development and manufacturing.

We would always welcome opportunities to collaborate with Korean biotech companies in the future. Korea has an abundance of talented scientists and skilled leaders, and I believe partnerships in innovative fields could contribute significantly to the country’s advancement on a national scale.”

“We understand that stabilizing the health insurance budget is a critical priority for the Korean government. Personally, I believe that striking a balance between financial stability and the advancement of innovative medicines is essential to introducing products with the potential to benefit patients into the market.

From a pharmaceutical company’s perspective, developing new drugs is fraught with challenges. Many drugs fail during clinical development, resulting in setbacks despite significant investment and uncertainty. This is an area that also deserves attention.

Through multifaceted discussions and efforts with the Korean government, we are working to find mutually agreeable solutions that improve patient access while addressing these challenges.

Above all, we never lose sight of what matters most—providing treatments to patients. Merck’s philosophy of ‘One for Patients’ reflects our commitment to prioritizing patient access and enhancing their quality of life.

While we are part of Merck as a company, our hearts are always with the patients. I often emphasize that ‘everyone becomes a caregiver to a patient at some point,’ which drives us to pursue every possible effort to improve access to treatments and find the best solutions for patients.”