Redhill Biopharma is claiming a phase III win with an unorthodox, antibiotic-based approach to treating Crohn’s disease. But a lack of efficacy at one year with its candidate, RHB-104, could put a spanner in the works.
Redhill executives brushed off concerns about the long-term effect of RHB-104 during a conference call today, saying that the MAP US trial had not been powered to show efficacy at 52 weeks. However, they admitted that one-year data would be needed for eventual approval. The company expects to have to carry out another phase III trial before it can file RHB-104 with regulators – and with just $36m in the bank it might have problems getting over the finish line.
Redhill’s shares on the Tel Aviv exchange jumped 40% when the company first announced that the MAP US study had met its primary endpoint, the proportion of patients in remission at 26 weeks.
But enthusiasm waned as the day went on and shares were flat by mid-afternoon, presumably decreasing the chances of a much-needed follow-on fundraising.
|MAP US trial results of RHB-104 in Crohn's (NCT01951326)|
|Remission at week 26 (CDAI <150)*||37%||23%||0.013|
|Response at week 26 (CDAI reduction by ≥100)||44%||31%||0.028|
|Remission at week 16**||42%||29%||0.019|
|Remission at week 52||27%||20%||0.155|
|Maintenance of remission from week 16 to week 52**||25%||12%||0.007|
|*Primary endpoint; **Not prespecified according to Clinicaltrials.gov; CDAI=Crohn's disease activity index; Source: company presentation.|
One cause for concern is the lack of clarity about the second phase III study. The Redhill execs would not give much information except to say that the company hoped to meet the FDA during the fourth quarter to iron out the trial design.
It is not clear when the one-year data would be collected, and Redhill’s medical director, Ira Kalfus, even suggested that it “would not be unreasonable” to have a 16-week rather than 26-week primary endpoint.
The company suggested to EP Vantage that the next trial could look at maintenance of remission from 16 weeks to 52 weeks, which it described as “more clinically relevant” than the standalone 52-week remission data.
Although Redhill claimed a win in the MAP US trial on maintenance of remission between 16 and 52 weeks, it did not give the figures for maintenance between weeks 26 and 52, the prespecified secondary endpoint according to Clinicaltrials.gov.
Another question is how the next trial would be funded. The Israeli company’s chief executive, Dror Ben-Asher, said the latest data could help Redhill attract a partner, and with cash running so short this might now be its only hope.
Mr Ben-Asher added that today’s data should help speed recruitment into the second pivotal trial and admitted that enrolment into the MAP US study had been slow – perhaps a sign that patients have been sceptical of RHB-104’s mechanism of action.
On the MAP?
The project is a combination of three antibiotics – clarithromycin, rifabutin and clofazimine – in a single oral capsule, which is designed to treat what Redhill believes is the underlying cause of Crohn’s disease: the bacterium Mycobacterium avium paratuberculosis (MAP).
The company plans to evaluate patient response in the MAP US trial according to MAP status, but does not yet have these data available.
The study evaluated RHB-104 on top of standard of care therapy, including biologics like Abbvie’s Humira and Johnson & Johnson’s Remicade. This was no doubt due to ethical considerations, but Redhill believes that the data support the eventual combination of RHB-104 with more established agents – as well as first-line use of the antibiotic, before corticosteroids.
The company stressed the unmet need in Crohn’s disease, but bigger players like Abbvie and J&J are unlikely to give up on this lucrative sector without a fight. And Redhill will need stronger long-term data to even get its project approved, let alone challenge the status quo.
This story has been updated to include company comments on maintenance of remission endpoints and Redhill's cash position.