A promising new drug could transform treatment for ulcerative colitis by targeting inflammation before it starts. Photo credit: Laurynas Me via Unsplash
Sometimes a drug is so promising that it creates waves in the field of chronic inflammatory diseases, bringing hope to patients and raising millions of dollars for research within just a few hours. This was the case for obefazimod, a molecule developed by the French company Abivax in collaboration with the renowned Institut Curie. Shares in Abivax rose by over 500% following the announcement of strong results of the Phase III obefazimod clinical trials.
Obefazimod was developed as a new way to treat chronic inflammatory bowel diseases such as ulcerative colitis.
Obefazimod was developed as a new way to treat chronic inflammatory bowel diseases such as ulcerative colitis. Ulcerative colitis is an inflammatory intestinal disease affecting between five and seven million people in the world, and one in every 227 people in the United Kingdom. Ulcerative colitis is an autoimmune condition: the body’s immune system mistakenly attacks healthy tissue located in the colon and in the rectum, resulting in inflammation. While the causes of these autoimmune attacks aren’t perfectly understood, scientists believe that it might be because the immune system incorrectly identifies unharmful microbiotic bacteria (naturally present in our intestinal tract) as harmful bacteria. This long-term condition’s main symptoms include recurring diarrhoea, stomach-ache, and extreme tiredness, alongside flare-ups characterised by mouth ulcers and arthritis. Existing treatments include steroids (synthetic versions of human-produced hormones) and immunosuppressants. However, these therapies do not cover all cases of ulcerative colitis and often come with adverse effects (such as difficulty sleeping, high blood pressure and eye conditions), making the arrival of obefazimod a major advancement for patients suffering from ulcerative colitis.
Obefazimod is so distinctive because unlike most anti-inflammatory drugs, such as steroids and immunomodulators, it acts upstream of inflammation. Specifically, obefazimod acts by binding to a protein called LARP7, which plays a role in processing non-coding RNAs (functional molecules that are not translated into proteins). The binding of obefazimod to LARP7 has a direct impact on certain microRNAs, which are small non-coding RNA molecules that regulate gene expression, causing many of them to become more stable. One such microRNA, miR-124, reduces the production of pro-inflammatory cytokines and increases the number of regulatory T cells, which contribute to reducing uncontrolled inflammation. As a result, inflammation is reduced before symptoms appear.
…miR-124, reduces the production of pro-inflammatory cytokines and increases the number of regulatory T cells, which contribute to reducing uncontrolled inflammation.
Prior to completing Phase III clinical trials, obefazimod passed Phase I (showing that the molecule isn’t toxic for humans) and Phase II trials (showing that the right dose has been found and that it doesn’t cause any major adverse effects). Phase III trials show that the molecule is significantly more effective than placebos and previous treatments. Nevertheless, more steps need to be taken before Obefazimod is released into the market. Abivax needs to send all preclinical and clinical data (Phases I–III) to the national or international regulatory agencies, such as the EMA (European Medicines Agency) or the FDA (Food and Drug Administration of the USA), who will conduct scientific and ethical reviews (checking that patients participating in trials gave informed consent and that data was collected honestly, among others). In the coming one to three years, these agencies will evaluate the efficiency and safety of obefazimod, before deciding whether to approve it for use in hospitals and pharmacies. If obefazimod enters the market, then it will enter Phase IV, also known as post-marketing surveillance, to detect any rare or long-term side effects.
If obefazimod enters the market, then it will enter Phase IV, also known as post-marketing surveillance, to detect any rare or long-term side effects.
The development of obefazimod represents a worldwide breakthrough in the treatment of chronic inflammatory diseases, and although its release into the market is not yet guaranteed its progress will undoubtedly be closely followed by the scientific community and patients alike.
