The speciality pharma business model has come under pressure in the past couple of years, but this has not put off Redhill Biopharma (NASDAQ:RDHL) (OTC:REDIF). “Our vision is to become a major speciality gastrointestinal player in the US in the coming years,” the Israeli group’s chief executive, Dror Ben-Asher, tells EP Vantage.
Redhill could move closer to that goal this year, with several important events coming up for its internal pipeline. It has three phase III projects, arguably the most interesting of which is RHB-104, an asset the group believes could target the underlying cause of Crohn’s disease. However, even if it works, going up against entrenched therapies like TNF inhibitors will not be an easy task for a small company.
The theory behind using RHB-104, a combination of three antibiotics in a single capsule, is that the chronic inflammation seen in Crohn’s is caused by a bacterium, Mycobacterium avium paratuberculosis (MAP).
Once the bacteria have been eradicated and the patient is in remission, the idea is that patients could come off the medication. This would make treatment with RHB-104 different from the current standard of care, chronic therapy with anti-TNF MAbs like Abbvie’s (NYSE:ABBV) Humira. As well as only treating the symptoms of autoimmune disorders, these products are linked with side effects including infection and cancer because of their effect on the immune system.
Mr. Ben-Asher believes that RHB-104 could not only avoid these issues, it could do so at a much lower price. However, it is hard to imagine the likes of Abbvie giving up this lucrative market without a fight.
Of course, Redhill first has to prove its theory, and it should soon get an early clue with interim analysis of the phase III MAP US trial due in the second quarter.
“There’s the possibility of an early stop for success. The drug needs to beat placebo with a p value of 0.003, so it’s highly ambitious,” Mr. Ben-Asher says. “It’s not a likely scenario – the likely scenario is that we’ll simply continue the study.”
If the study is not stopped, enrolment is due to complete by the end of the year and data should be available towards the end of 2018. The primary endpoint is remission at week 26, measured by the Crohn’s disease activity index (CDAI) score.
Redhill believes that other autoimmune disorders could also be triggered by MAP, and has already carried out a phase IIa study of RHB-104 in multiple sclerosis; it is also looking at RHB-104 in lupus and psoriasis.
If the idea that a bacterial infection can cause Crohn’s and MS sounds far-fetched, it is worth considering the case of Helicobacter pylori. For years, gastric ulcers were thought to be caused by factors like diet and stress, until a link with the bacterium was shown in the 1980s.
Another of Redhill’s projects, RHB-105, is targeting H pylori that has started to develop resistance to current therapy. “The standard of care treatment fails to eradicate H pylori in 30-50% of cases,” says Mr. Ben-Asher.
Today, therapy involves a combination of two antibiotics and a proton pump inhibitor: clarithromycin or metronidazole, amoxicillin and omeprazole. RHB-105, another triple therapy in a single pill, replaces the clarithromycin/metronidazole component with rifabutin, which has not been approved for H pylori.
An upcoming confirmatory phase III trial, slated to start in the second quarter, will compare RHB-105 with standard of care. RHB-105’s first phase III trial returned positive topline results in 2015.
Explaining the long delay between finishing that trial and beginning the new phase III, Gilead Raday, Redhill’s chief operating officer, says the study was not fully completed until last year. Since then, the company has been communicating with the FDA to agree the design of the new trial, he adds.
But neither of these products is likely to be the first of Redhill’s current pipeline to gain approval – that will likely be Bekinda, also known as RHB-102, which is in a phase III trial in gastroenteritis with initial results due in the second quarter. If positive, Redhill hopes that this will be enough to support a US filing.
Bekinda is a once-daily formulation of the 5-HT3 antagonist odansetron, the active ingredient of Novartis’ (NYSE:NVS) now off-patent Zofran, used to treat chemotherapy-associated nausea and vomiting. Redhill believes that its project could avoid the peaks and troughs of immediate-release drugs that need to be taken two to three times daily.
And, according to Mr. Raday, no 5-HT3 antagonists are currently approved in gastroenteritis. Redhill is also testing Bekinda in irritable bowel syndrome with diarrhoea (IBS-D), with a phase II trial expected to read out mid-year.
However, links between odansetron and birth defects have been alleged, which could limit Redhill’s market in these arguably less severe indications.
Redhill is also about to start marketing Concordia’s irritable bowel syndrome therapy Donnatal under a co-promotion agreement signed earlier this year, and it hopes to license more GI assets in the coming months, Mr. Ben-Asher says.
The company had just $66m in cash as of the end of December. With all these activities coming up, it might need to raise some more money soon.