Hopes of seeing an approved treatment for the inflammatory bowel condition pouchitis have been dashed as the UK company Atlantic Healthcare’s RNA drug has proved ineffective in a phase III trial.
The trial tested Atlantic Healthcare’s RNA drug alicaforsen as a treatment for patients with pouchitis. Patients with this condition have their colon surgically replaced by a pouch made from the small intestine, which gets inflamed, causing bloody diarrhea and up to 20 toilet trips per day.
In the phase III trial, Atlantic Healthcare compared the effect of daily alicaforsen enemas with a placebo treatment in 138 pouchitis patients for six weeks. Unfortunately for Atlantic, the drug failed to meet the primary endpoints of the trial, which were achieving remission and reducing the patient’s toilet trips. However, the company reported that certain groups of patients may have benefitted more than others, and, bearing this in mind, will discuss the regulatory approval options with the FDA.
Originally developed by the US company Ionis Pharmaceuticals, alicaforsen is an antisense oligonucleotide drug. These drugs bind to a specific messenger RNA molecule that carries the instructions to create a certain protein, blocking its production. Alicaforsen was designed to reduce inflammation by targeting the messenger RNA encoding a protein involved in inflammation.
The first antisense oligonucleotide drug was approved in 1998, and several more have entered the market since then. These drugs have shown potential for treating rare diseases lacking effective drugs. For example, 2016 saw the approval of US company Sarepta Therapeutics’ antisense drug Exondys 51, the first treatment for the rare genetic disease Duchenne muscular dystrophy. Later that year, Biogen and Ionis Pharmaceutical’s antisense drug Spinraza became the first approved drug for the rare disease spinal muscular atrophy.
Despite the phase III setback, Atlantic Healthcare seems determined to take the drug to market. Atlantic Healthcare is also testing the drug’s effect in other inflammatory bowel conditions, such as for ulcerative colitis in phase II, and Crohn’s disease in phase I. It remains to be seen whether the drug will be more effective in these other conditions than it was in pouchitis.
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