Revolutionary new oral medicine to treat inflammatory bowel disease developed by industry collaboration

The oral infliximab drug delivery system was developed by a collaboration between Intract Pharma, Pharmidex, Quay Pharma and deep tech innovation organisation CPI.

CPI, an independent deep tech innovation organisation, has worked with Intract Pharma, Quay Pharma, and Pharmidex to successfully repackage the biologic drug infliximab into a safer, more effective and more convenient oral capsule.

Never before has an oral monoclonal antibody treatment been clinically viable and commercially available. Now ready for human clinical trials, this new oral drug product could change that, along with the lives of millions of people living with Crohn’s disease and ulcerative colitis – the two main types of inflammatory bowel disease (IBD).

For most people with Crohn’s and colitis, the monoclonal antibody therapy infliximab is the first-choice biologic treatment to control the disease. But receiving this gold-standard therapy can be painful, time-consuming, and cause adverse effects such as immunosuppression.

Infliximab is usually administered by intravenous infusion – requiring 2 hours in hospital each time, alongside routine patient monitoring. Developing an oral delivery method is challenging. Drugs must survive the digestive system’s harsh environment and reach the colon intact to be most effective.

Formulating infliximab as an oral capsule is transformational. If human clinical trials are successful and once on the market, patients will be able to simply wake up in the morning and swallow a tablet. The oral version of infliximab is more targeted and has fewer side effects than the injectable product. It is also cheaper to produce and deliver, thereby reducing demands on healthcare resources.

Silvia Matiz, Formulation Scientist at Intract Pharma, who managed the project, highlighted the impact of this collaboration on the development of orally administered biological medicines: “Over the past years, Intract has been working really hard in the development of technologies to allow for oral delivery of biologics – the ‘holy grail’ in the pharmaceutical industry. Protein-based therapeutics are generally unstable in the harsh conditions of the gut and rapidly degrade before being able to exert any effect.”

The innovative oral delivery technology packages infliximab in a dual-purpose manner. The Phloral™ coating precisely releases the antibody in the colon, the main site of inflammation in IBD patients. The Soteria ® technology prevents the digestive enzymes from prematurely degrading the drug, maximising uptake in the diseased tissue.

The consortium was set the challenge of developing Intract Pharma’s technologies into a capsule prototype containing infliximab. Using in-house bioprocessing expertise and state-of-the-art biologics manufacturing and formulation facilities, CPI helped optimise the oral infliximab product and prepared it for scale-up and manufacture.

John Arthur, Director of Medicines Manufacturing and Biologics at CPI, said: “Every day at CPI we work together with industry partners to create lasting impact through deep tech innovation. Through our collaboration with Intract Pharma, Quay Pharma and Pharmidex we were able to provide a solid proof-of-concept to take the novel oral infliximab product to clinical trials and bring a transformative treatment one step closer to reality for the millions of people with Crohn’s and colitis around the world.”

The ambitious, collaborative project also included pre-clinical studies conducted by Pharmidex and scale-up by Quay Pharma.

Silvia Matiz added: “Thanks to the expertise in drug development and manufacture brought by the colleagues from Quay, CPI and Pharmidex, we successfully developed a scalable manufacturing process for oral antibody products, taking the oral Infliximab one step closer to the clinic.”

Mo Alavijeh, Director at Pharmidex, said: “IBD is a lifelong, often debilitating condition, with no cure, which affects adults and children of all ages. Over 500,000 people in the UK have IBD, with an estimated cost to the NHS of £720 million.

“We are delighted that the Pharmidex Oncology team, headed by Dr Christopher Ireson, was part of this innovative project working closely with Intract Pharma, Quay Pharma and CPI to enable this project to progress swiftly towards clinical development, ultimately leading to reducing the suffering of IBD patients.”

Mike Frodsham, Chief Technical Director at Quay Pharma, added: “We are excited to have been part of this early-stage collaborative project. Oral delivery of large molecules poses multiple challenges; this project goes some way to addressing the future potential for targeted delivery using scalable manufacturing processes. We look forward to seeing the outcome of future studies conducted by Intract and hope for a more manageable dosage form for Crohn’s disease patients in the future.”

In 2018, the partnership secured more than £1.4 million in funding through UK Research and Innovation’s Industrial Strategy Challenge Fund for innovative projects in medicines manufacturing and contributions from industry partners. The innovative manufacturing approaches developed during the project could help formulate and stabilise other biologic medicines in the future.

Nicholas Medcalf, Deputy Director of UKRI’s medicines manufacturing challenge, said: “Two of the key aims of UK Research and Innovation’s medicines manufacturing challenge are to improve commercial viability and to develop methods for scale-up. That’s why, in 2018 we provided more than £1.1 million in funding to this project. I am pleased to see our investment has supported the production of this novel drug delivery method, which will improve the lives of patients, and the innovative processes that could help formulate and stabilise other biologic medicines in the future.”