Today’s post took me much longer than normal to write. I had a lot of difficulty finding a company that fit my normal criteria – established, but not an industry leader; at least one phase 3 candidate in the pipeline; and so on. I think, however, that the effort was worthwhile. Redhill Biopharma ($RDHL) has a handful of drugs which are very intriguing to me, and I hope to cover their drug for Crohn’s Disease in a future post. Today, though, I’m writing about Redhill Biopharma ($RDHL)’s drug BEKINDA (not an acronym, just an all-caps name for some reason). As always, if you don’t care about the details, feel free to scroll to the end.
BEKINDA, formerly known as RHB-102, is an extended-release formulation of the generic drug ondansetron (commonly known under the brand name Zofran). Ondansetron is an anti-emetic (anti-vomiting) drug, and is used to prevent vomiting in patients undergoing cancer treatment or surgery. Ondansetron is also frequently prescribed off-label for children suffering from acute gastroenteritis (AGE). AGE is something of a catch-all term for “an upset stomach caused by some sort of bug.” When people say “stomach flu,” they’re talking about AGE.
Interestingly, although the use of ondansetron has been studied fairly extensively in children suffering from gastroenteritis, there is almost no data on the use of ondansetron in adults suffering from AGE. And even in children, the use of ondansetron is technically off-label. With all of that background, hopefully it makes sense that RDHL’s formulation of ondansetron, BEKINDA, is intended to be a better method of treating the stomach flu.
While I was evaluating the BEKINDA’s chances in the phase 3 trial, I decided that approval would come down to three things:
- Is the drug likely to be effective?
- Is the drug likely to be safe?
- Did RDHL establish a realistic study protocol?
Is BEKINDA likely to be effective in treating AGE in the phase 3 trial?
In short: yes. As mentioned above, ondansetron is already widely used to treat children with gastroenteritis. A well-designed study found that ondansetron was – in nearly every conceivable measure of effectiveness – statistically superior to both placebo and a European anti-vomiting drug known as Domperidone in treating AGE.
The success of BEKINDA, which is simply a delayed-release pill containing ondansetron, is probably presaged by these results. Although the data above was for children, there’s no real reason why it wouldn’t hold true for adults, as well. The one caveat here – and I’ll return to this later – is that the data from the table above was taken during the emergency department (ED) visit, meaning it was short-term data.
Is BEKINDA likely to be safe in the phase 3 trial?
To summarize again: yes. There are a few contraindications for ondansetron, but the advantage of reformulating a well-known drug is that all of the kinks have mostly been worked out (or at least discovered). I forsee no significant safety issues in this trial.
Did RDHL establish a realistic study protocol? Will BEKINDA pass phase 3?
This is always the tricky one to answer. Earlier in this article I mentioned that most (if not all) of the data for ondansetron is collected over a very short time period – usually over the course of a few hours – while the study protocol is a bit longer than that. The primary outcome measures of the BEKINDA phase 3 “GUARD study” are the proportion of patients
- without further vomiting,
- without rescue medication, and/or
- who were not given intravenous hydration
from 30 minutes after the first dose until 24 hours later.
The length of time might be a problem, because when the researchers from the study cited above followed up 48 hours after the emergency room visits, they found that there was no longer any difference between the three conditions.
This isn’t really surprising, considering the nature of the drug and the fact that any kids taken to the emergency department for vomiting were likely too sick to get better in one day. The question, though, is whether BEKINDA’s extended release formulation will be enough to overcome this hurdle.
Without phase 2 data to draw on, I turned to the next best thing: a bioavailability study. The only study I could find tested RHB-102 (which became BEKINDA) against the dose of ondansetron used in chemotherapy. Over the course of 5 days, the bioavailability of BEKINDA was either equal to or better than the routine dose. And even better, when researchers tested blood concentrations 24 hours after the initial dose, BEKINDA beat out a non-extended release equivalent dose.
Ultimately, I think that yes, the GUARD study is realistic, and RDHL will likely take home a phase 3 approval.
If BEKINDA posts good data (expected to take place sometime in the second half of this year), it will become the first drug in its class to treat acute gastroenteritis. If the study posts particularly strong results, it may even be possible that just the one study will be sufficient for FDA approval. To summarize, ondansetron (the drug making up BEKINDA) is effective, the study protocol is achievable, and the extended-release formula appears to work.
Based on what I’ve written here, I believe that $RDHL is a buy, for at least until the BEKINDA data is released.
If you liked this article, please subscribe to the newsletter – in addition to seeing new posts, my subscribers also get updates, news, and advice that isn’t available to people just reading the articles.
Prediction: Phase 3 Approval
The drug underlying BEKINDA has already been demonstrated to be effective, and a bioavailability study suggested that the extended-release formulation works.