Merck & Cie

“WE’VE INVESTED SEVERAL MILLION SWISS FRANCS IN ARFOLITIXORIN’S RESEARCH AND DEVELOPMENT”

In specific terms, Merck & Cie have helped with the manufacture of arfolitixorin´s active ingredient, MTHF. But if we look at the big picture, how have you helped there?

For several decades now, Merck has been building up a comprehensive
body of folate chemistry expertise – an asset that made our partnership possible in the first place. We have invested several million Swiss francs in arfolitixorin’s research and development, including the synthesis, analysis and formulation of the active pharmaceutical ingredient. The development of arfolitixorin’s complex active pharmaceutical component
to the quality required was a huge challenge and demanded a great amount of effort. Our hard work bore fruit, however, and we eventually managed to synthesise a very pure and stable form of the chemically complex folate compound that now bears the name, arfolitixorin.

If we look ahead, what is your role in the arfolitixorin project?

Our role is to focus on production of the active pharmaceutical ingredient. After the successful production of the first pilot batches and validation of the analytical methodologies, we are now ready to produce the active pharmaceutical ingredient, arfolitixorin, on a commercial scale. We also conduct analytical work ahead of the launch of a pharmaceutical product and also provide support by preparing the necessary documentation for the health care authorities (e.g. chemistry, manufacturing and controls (CMC) of the regulatory documentation) as part of the ongoing clinical pivotal study.

How do you handle the project´s risks?

Merck & Cie will focus continuously on the development of arfolitixorin,
a concept based on solid scientific grounds and where the active pharmaceutical ingredient enjoys strong patent protection.

What potential do you see in arfolitixorin?

Merck has a leading global role as a manufacturer of high quality folates for pharmaceutical and nutritional supplement applications. The active ingredient, arfolitixorin, has an important part to play here.

We have identified a strong clinical need for new molecules to improve the treatment of colorectal cancer. The specific product properties of arfolitixorin in combination with 5-fluorouracil (5-FU) makes it the perfect candidate for specific and strong functionality in preventing cell division and tumour growth. Given this scientific background and based on the patent situation, we have identified substantial economic
potential if the clinical effects of arfolitixorin can be confirmed
by the phase III AGENT study.

Our sales forecast planning classifies arfolitixorin as a product which can, in future, make a significant financial contribution to our folate operations.

Skövde Sjukhus

“GREAT NEED TO POTENTIATE TREATMENTS”

Johan Haux’s clinic at Skövde Sjukhus is one of the clinics taking part in the ISO-CC-005 study.

“The patients being treated have metastatic colorectal cancer, so surgery is not an option. Even if the number of patients enrolled in the 005 study at a single clinic like ours don’t constitute a statistically reliable sample, the efficacy of arfolitixorin for the patients receiving the drug was so apparent to me, and the adverse effects profile seemed to be the same as for leucovorin (folic acid), and not more pronounced. In the study, arfolitixorin specifically replaced leucovorin, which is the standard treatment nowadays in combination with 5-FU, often together with other cytotoxic drugs, such as oxaliplatin and irinotecan. I’m very excited to see the results of the phase III AGENT study. If the efficacy can be confirmed, if arfolitixorin is demonstrated to work and to potentiate cancer treatments without more/other unfavourable side effects, then this is a very interesting drug indeed. For many of the gastrointestinal types of cancer, 5-FU in combination with leucovorin lies at the core of the treatments and if arfolitixorin turns out to be better, I would, speaking as an oncologist, like to go further and conduct trials on other forms of cancer where there is also a great need to potentiate the anti-cancer effects. There is a huge unmet need here, particularly for those patients who are currently incurable.”

Johan Haux, MD, Ph.D. Senior Physician, Skaraborg Hospital,
oncologist specialising in gastrointestinal cancer. Member of
the Swedish Gastrointestinal Cancer Association (GOF) and
Chairman of the Swedish Study group for Pancreatic Cancer
(SSPAC)