At Merck KGaA, Darmstadt, Germany, patients are at the forefront. That’s why we invest substantial amounts in new therapies – for example to improve the treatment of cancer or multiple sclerosis (MS). At our research and development hubs in Darmstadt, Boston, Beijing, and Tokyo, around 3,000 employees work in global networks for the benefit of patients.
The research spirit of the Merck family of pharmacists was obvious early on. For instance, in the 19th century Emanuel Merck worked intensively with plant-based natural substances. He succeeded in isolating alkaloids such as morphine in pure form. And in 1827, when he offered these active ingredients for the first time in the “Cabinet of Pharmaceutical and Chemical Innovations”, he achieved a quantum leap – from a pharmacy to a research-based pharmaceutical and chemical company. Soon the portfolio encompassed hundreds of products, for example as of 1894 the innovative thyroid medicine Thyreoidinum siccatum. And today, the discovery and development of innovative medicines to benefit patients is of utmost importance to us, and we conduct research and development around the world. This applies in particular to the four closely linked R&D hubs located on three continents and operated by our Healthcare business sector.
“Obtaining approval of a new medicine in the individual markets is a long journey.”Bodo HammesDirector Global Regulatory Lead Mavenclad®
scientists and clinical researchers work at our R&D center at our headquarters in Darmstadt
More than 1,500 scientists and clinical researchers work at our R&D center at our headquarters in Darmstadt. Bodo Hammes is one of them. Hammes is a pharmacist but doesn’t work in a laboratory. Instead, he handles the regulatory strategy for the approval of medicines. He is responsible for Immunology and Neurology and is currently focusing on the MS product Mavenclad® (cladribine tablets). In 2017, we received approval in the European Union, Canada and Australia for this new medicine to treat relapsing forms of multiple sclerosis – a major success. Multiple sclerosis is one of the most common chronic neurological diseases, affecting around 2.3 million
million people worldwide have ms
people worldwide. “Obtaining approval of a new medicine in the individual markets is a long journey. Intensive cooperation with the regulatory authorities is therefore extremely important on the home stretch since we want patients to benefit from effective new treatments as soon as possible,” says Hammes. Pharmaceutical researchers must first identify an active ingredient candidate that then undergoes extensive laboratory tests in preclinical development. Only when preclinical testing succeeds can the three phases of clinical development and testing in humans proceed. The development of a drug from the first idea until its final approval usually takes about 13 years. For the marketing authorization of Mavenclad®, more than 10,000 patient years of data from approximately 2,400 patients enrolled in the clinical trial program were taken into consideration, including patients with a follow-up time of up to eight years. The regulatory authorities review the study data closely and evaluate the benefit-risk ratio of the drug.
“We are playing a game of chess against cancer. It’s a tough opponent, but with the right moves, we can translate them into patient benefits.”KIN-MING LOHead of Redirected Immunotherapy
Our dossier for Mavenclad® encompasses more than 200,000 pages, from the precise manufacturing information and countless study results, tables and references up to the package leaflet. “To run a project as big as this one, you need an extremely knowledgeable and passionate, interdisciplinary team – we have that and I am proud to be part of it,” says Hammes with a smile.
R&D Professionals in Boston
The dedication and expertise required for the research and development of new medicines is something Kin-Ming Lo is well-versed in. Originally from Hong Kong, Lo has been working in research and development for over 30 years and is a scientist at our R&D hub in Billerica, Massachusetts, just outside of Boston. At this highly modern facility, more than 500 scientists work in the areas of neurology, immunology, immuno-oncology, and oncology. A major focus of immuno-oncology is on developing breakthrough immunotherapies for cancer. “We are playing a game of chess against cancer. It’s a tough opponent, but with the right moves, we can translate them into patient benefits,” says Lo. In cooperation with Pfizer, we achieved an important step forward in 2017. The new oncology medicine Bavencio® (avelumab) was approved in the United States, the European Union, Japan, Switzerland and Canada for use in metastatic Merkel cell carcinoma (MCC), a rare and aggressive form of skin cancer. In addition, the U.S. Food and Drug Administration granted approval of Bavencio® for the treatment of patients with locally advanced or metastatic urothelial carcinoma (UC). Bavencio® is a human antibody that is directed against the PD-L1 (programmed cell death ligand 1) protein, a key component of an immunosuppressive network that dampens the ability of T cells to attack tumors. The clinical development program encompasses around 30 clinical trials with more than 7,000 patients who are being studied across more than 15 tumor types.EXPLORE MORE
“We take the raw material of the starting molecule and turn it, atom by atom, into an actual drug. For Bavencio®, we also determined how the drug acts, attacking the tumor cell to disable the tumor’s defense system.”Vanita SoodHead of Drug Structure, Prediction and Design
PATIENTS IN 30 CLINICAL TRIALS
Apart from metastatic MCC and UC, these include breast, lung, gastric, ovarian, and head and neck cancer as well as renal cell carcinoma. Vanita Sood and her team also contributed to the successful development of Bavencio®. Sood, a computational biologist who works both in Billerica and at global headquarters in Darmstadt focuses on turning therapeutic ideas into molecules. “We take the raw material of the starting molecule and turn it, atom by atom, into an actual drug. For Bavencio®, we also determined how the drug acts, attacking the tumor cell to disable the tumor’s defense system,” Sood explains. She is currently working to harness machine learning and artificial intelligence with the aim of accelerating the ability to predict which molecules out of trillions have the right properties to become safe and effective drugs. Back to Kin-Ming Lo. While working on Bavencio® in its early R&D days, he already began thinking of strategies to improve its activity. “Cancer cells employ multiple immunosuppressive pathways to escape detection by the immune system. If we suppress more than one of the mechanisms that tumors use to avoid the immune system, we have a better chance of killing the cancer,” says Lo. This has led to the development of a bifunctional antibody fusion protein and other candidates in the R&D pipeline.
But for now, everyone involved is pleased that Bavencio® is being approved for the treatment of Merkel cell carcinoma in a growing number of markets. This is also the case in Japan. Ryoko Miyauchi, a pharmacist, has been working for eleven years at the research and development hub in Tokyo, which is located in a quiet and picturesque part of the Japanese capital. Together with her colleagues, she worked on the regulatory submission of Bavencio®, which was the first human anti-PD-L1 antibody to be approved in Japan – and also the first in Asia. The fact that this happened in a short period of time is not a matter of course. Just like every other market, Japan has very specific requirements for the approval of medicines. “We worked very closely with our global network to prepare the Japanese dossier for Bavencio®. In the process, it was very stimulating to get to know the different cultures and people. We’ve not only benefited from working together, but also made new friends,” says Miyauchi.
This cross-border team spirit is also confirmed by Yue Huang: “After having lived for nearly 20 years in the United States and Switzerland, I returned to my homeland of China, and I am very happy to still be working with people from many different cultures who are extremely dedicated and committed to the work we’re doing.” From the 21st floor of the modern office building that houses the Chinese research and development hub of our company, the Head of Clinical Pharmacology in China has a good view of the bustling metropolis of Beijing. Yue Huang is also working intensively on Bavencio® and its potential approval in China. Another advance relates to the oncology drug Erbitux®, following the positive Phase III trial as a first-line treatment for colorectal cancer in China. The research and development strategy at the Beijing hub is mainly focused on bringing innovative and established global assets to China by leveraging the fast-evolving scientific and regulatory environment. “We are working to enable Chinese patients to benefit sooner and more extensively from our drug pipeline,” says Yue Huang.
Our vision of giving as many people as possible around the world access to innovative medicines is thus increasingly becoming a reality.
“We are working to enable Chinese patients to benefit sooner and more extensively from our drug pipeline.”YUE HUANGHead of Clinical Pharmacology China