Worldwide recognition for therapy of chronic intestinal inflammation developed in Kiel
An important milestone for the drug “Olamkicept”, developed by researchers from Kiel, on the way to approval: The high-ranking Journal of the American Medical Association (JAMA) has published a phase II study confirming the efficacy and tolerability of the novel compound in patients with ulcerative colitis. JAMA is the most widely read medical journal in the world.
“Congratulations on this success,” says Prof. Dr. Dr. h.c. mult. Jens Scholz, Chief Executive Officer (CEO) of the University Hospital Schleswig-Holstein (UKSH), “because it shows impressively that here in Schleswig-Holstein we succeed in bringing the results of cutting-edge medical research directly to the bedside as innovative therapy.” Prof. Dr. Joachim Thiery, Dean of the Medical Faculty of Christian-Albrechts-Universität zu Kiel (CAU), adds: “The successful phase II study in JAMA now gives new hope to many patients with inflammatory diseases. The path from the discovery of a new biochemical principle to clinical application follows our guiding principle of sustainability in medical research. This success is a milestone in precision medicine.” Prof. Dr. Stefan Schreiber, Director of the Clinic for Internal Medicine I at UKSH, Kiel Campus, says: “The fact that the functioning of our therapy mechanism is now attracting international attention is very good news for patients, because approval is within reach.”
Prof. Schreiber is also the spokesperson for the Cluster of Excellence “Precision Medicine in Chronic Inflammation” (PMI) and Director of the Institute for Clinical Molecular Biology at CAU and UKSH, and together with his teams has significantly advanced the development of the active substance. The inventor of the molecule, the Kiel biochemist Prof. em. Dr. Stefan Rose-John, is proud of the success that the decades of preliminary work could actually be transferred to humans. “This is by no means a matter of course. Many molecules work in animal models, and only rarely can the successes achieved there be transferred to humans. With the biochemical principle we have found, we have opened the door to a whole new inflammatory medicine,” says Professor Rose-John.
Ulcerative colitis is a chronic inflammation of the colon, usually occurring in episodes, characterised by recurrent diarrhoea, intestinal bleeding and colic. In Germany, more than 150,000 people are affected. The inflammation is based on a misdirected immune reaction in which the immune system mistakenly attacks cells in the colon. Due to the individual differences in the severity of the disease, the drugs available to date have only been effective for a few sufferers and often cause side effects, so that new therapeutic approaches are urgently needed to help sufferers for whom previous therapeutic approaches have been unsuccessful.
Olamkicept is based on a novel mode of action that none of the approved drugs for ulcerative colitis have used so far. When inflammation occurs, as it does in ulcerative colitis, the body releases more of the signalling molecule interleukin-6 (IL-6). However, if – as with previous drugs – all the effects of IL-6 are blocked, this very successfully dampens the inflammation, but at the same time the immune system can be so severely suppressed by the blockade of IL-6 that the body becomes much more susceptible to infections.
What is special about olamkicept is that it specifically blocks the so-called IL-6 trans-signalling signalling pathway. This signalling pathway and also the blocking protein sgp130Fc were discovered by the Kiel biochemist Prof. Dr. Stefan Rose-John and he has done pioneering work in their research. Together with researchers from the Cluster of Excellence “Precision Medicine in Chronic Inflammation”, he further developed the sgp130Fc protein, which could finally be tested in clinical trials as the drug candidate olamkicept. A first study with 16 patients at UKSH, Campus Kiel, in 2021 was able to prove the basic functioning of the therapy mechanism of olamkicept.
The study now published in the renowned scientific journal JAMA was once again able to demonstrate the efficacy and tolerability of olamkicept in patients with ulcerative colitis from various Asian countries. In the phase II study conducted by I-Mab Biopharma, 91 patients with moderate or severe ulcerative colitis received either a placebo, 300 mg of olamkicept per day or 600 mg of olamkicept per day for 12 weeks. The study was double-blinded, i.e. neither the patients nor the treatment providers knew who was in which group. After the twelve weeks, significantly more people who had received 600 mg of olamkicept showed a clinical response (improvement in symptoms or endoscopic findings). Symptoms disappeared completely in about 21 per cent (compared to 0 per cent in the placebo group) and healing of the intestinal mucosa was observed in almost 35 per cent (compared to three per cent in the placebo group).
The results were first presented at the renowned international gastroenterology conference Digestive Disease Week in December 2021 and published in the March 2023 journal JAMA. “The fact that the international scientific community has now recognised the study results in the peer review process is a major milestone for our research, whose declared goal is to bring results from basic research into clinical application,” says Prof. Schreiber. The development of olamkicept as a drug is being carried out by the pharmaceutical company Ferring as a licensee together with the Kiel biotechnology company CONARIS Research Institute AG and the Chinese pharmaceutical company I-Mab Biopharma.
Original publication: Shenghong Zhang, Baili Chen, …, Stefan Schreiber & Minhu Chen: Effect of Induction Therapy With Olamkicept vs Placebo on Clinical Response in Patients With Active Ulcerative Colitis – A Randomized Clinical Trial; JAMA. 2023;329(9):725-734. doi:10.1001/jama.2023.1084
For questions from journalists, please contact:
University Hospital Schleswig-Holstein, Campus Kiel
Department of Internal Medicine I, Prof. Dr. Stefan Schreiber
Tel.: 0431 500-22200, Stefan.Schreiber@uksh.de