RHB-104 Phase 3 data

Redhill Biopharma ($RDHL): Phase 3 Drug candidate RHB-105 likely to succeed, RHB-104 possible

This week I’m hoping to wrap up my two-part series on Redhill Biopharma ($RDHL). Previously I wrote about RDHL’s drug BEKINDA, which I believe is likely to pass its phase 3 trial. RDHL has two other late-stage drugs in the pipeline: RHB-105, which is designed to treat the bacteria which causes stomach ulcers, and RHB-104, which hopes to treat Crohn’s disease.

After doing some research, I believe that RHB-105 is also likely to pass the confirmatory phase 3 trial, which is scheduled to begin later this year. RHB-105 is a combination therapy designed to treat antibiotic-resistant strains of the bacteria that causes ulcers, known as Helicobacter pylori or H.pylori. Essentially, RHB-105 is a single pill containing two antibiotics and a proton pump inhibitor (acid reflux drug). The scientists at Redhill hope that the combination of drugs will be better than the current standard of care – one antibiotic and a proton pump inhibitor. It appears that they may be correct.

$RDHL’s Drug RHB-105: Likely to Pass Confirmatory Phase 3 Trial

Earlier this month, RDHL announced positive data from RHB-105’s initial phase 3 study. Redhill is planning to run a second confirmatory phase 3 study, which will probably begin sometime in June or July of this year. The initial study was well-designed: The placebo was a good match for the active intervention, they used two common methods of diagnosis to confirm the presence of H.pylori and patients who dropped out or did not complete the study were counted as failures.

In the study, RHB-105 eradicated H.pylori infection in 89% of the treated patients. This is significantly better than the standard of care’s success rate, which is roughly 70%. What’s more, at the end of the study they allowed the placebo group to be treated with the standard of care, and only 63% of that group were successfully cured of H.pylori, suggesting that 70% may have been an optimistic estimate.

So, with the first phase 3 trial RHB-105 demonstrated that it is significantly more effective than placebo (unsurprising) and significantly more effective than an estimate of the standard of care (somewhat surprising). As a follow up, the confirmatory trial will be about 4 times larger and will pit RHB-105 directly against the standard of care. There’s some room here for failure. Although I think it’s very unlikely that RHB-105 will perform worse than the standard of care, it’s possible that there won’t be a statistically significant difference between RHB-105 and the standard. I suspect that’s why the researchers are making this trial so much larger – statistically, a large trial is more likely to pick up on small differences between two conditions.

Even with that said, the strong study design and impressive results from the first phase 3 trial make me think that another pass is likely.

Prediction for RHB-105: Confirmatory Phase 3 Approval

Although it will be more than a year before we see any data from the confirmatory phase 3 trial for RHB-105, I believe that the ultimate result will be a success. I’ll update this post if something happens to change my mind.

$RDHL’s Drug RHB-104: Potential to Pass Initial Phase 3 Trial

Unfortunately, there’s not enough data for me to be certain about the third drug candidate, RHB-104. There is a strong theoretical grounding, and I believe it is highly possible that RHB-104 will pass, but I’m not quite confident enough to say “likely.” Part of the issue is the particular nature of Crohn’s disease – although we’ve identified some of the risk factors, nobody has yet proven exactly what causes Crohn’s. And because we don’t know what causes Crohn’s, nearly all of the treatments for the disease treat the symptoms, instead of the cause.

Redhill hopes to be one of the first companies with a treatment for the cause of Crohn’s. RHB-104 is, like -105, a combination therapy. In this case, the combination is of three separate antibiotics. There’s been some very recent research suggesting that combining antibiotics like this may lead to some synergistic effects; that using small doses of multiple antibiotics at the same time is better than using large doses of just one antibiotic. The sum, in effect, is greater than the parts – or at least, that’s what RDHL is hoping.

The three antibiotics in RHB-104 are all aimed at treating a particular strain of bacteria known as MAP. As you’ve probably guessed, the researchers at Redhill Biopharma believe that MAP plays an integral role in causing Crohn’s disease. It’s well-known that MAP causes Johne’s disease in cattle, which is a very similar ailment. Modern research has also conclusively demonstrated that people with Crohn’s have a much higher rate of MAP infection than people without Crohn’s.

Although none of the above is conclusive (or even demonstrates causation), there has been some research suggesting that treating MAP infection may help Crohn’s symptoms:

Effectiveness of RHB-104
Taken from Borody et al (2002), Digest Liver Dis 34:29-38

In addition, a statistical reanalysis of an Australian phase 3 study using anti-MAP therapy to treat Crohn’s disease suggested that anti-MAP therapy may be significantly more effective than placebo. However, there are some inherent issues in reanalysis, and I wasn’t able to find out whether the reanalysis was funded by RDHL.

RHB-104 Phase 3 data
Taken from Behr and Hanley (2008), Lancet Infectious Diseases 8:344

As you can see, there’s some fairly compelling evidence suggesting that MAP might be implicated in Crohn’s. If so, RDHL’s drug will probably be effective, as there’s some separate fairly compelling evidence suggesting that RHB-104 is effective against MAP. I never like to stack assumptions atop assumptions like that, though, which is why I’m ultimately going to say that this is possible, not probable.

Personally, I don’t think that MAP is exclusively responsible for Crohn’s. I suspect that Crohn’s disease is a combination of genetic susceptibility and infection from a handful of possible causes.  Even so, RHB-104 just might work. We should see interim data sometime within the next few months.

Prediction for RHB-104: Possibility for Phase 3 Approval

Unfortunately, I don’t feel comfortable putting the stamp of approval on this one. Even so, with BEKINDA and RHB-105 likely to receive approval, I think $RDHL is a buy.

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4 thoughts on “Redhill Biopharma ($RDHL): Phase 3 Drug candidate RHB-105 likely to succeed, RHB-104 possible”

  1. Why are you saying that Bekinda`s phase III data readout will be in Q3 while their last official announcement said Q2 (1st Q financial results)?

    1. I’ve found that it’s typically best to build in a bit of a safety margin when talking about data readouts. There are a lot of things that can delay a company’s being able to present data. Thanks for the comment!

  2. Hello,

    nice Job with that.

    Could write something about Macrilen from AEZS and Palatins drug Rekynda ?

    Best Regards

    1. Thanks for the suggestions! I will add both of those to my list of companies to check out, but to be honest I’ve gotten so many requests that I can’t address them all. I will do my best, though!

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