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Post by JHam on Jun 14, 2017 16:40:15 GMT
I want to also know why the placebo was so high. Is it just because that with an indication like gastroenteritis vomiting can stop on its own at different times in different people?
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Post by JHam on Jun 14, 2017 17:54:50 GMT
Check this out from 2015 by Jason N. Not sure why I never discovered this until now, but he answers my question. www.bionapinc.com/2015/11/bekinda-development-continues-in-phase.htmlFirst, this is from study done in 2002 in children. Very similar results to the BEKINDA data released today: A study by Reeves JJ, et al., 2002 enrolled 172 patients (average age 5.3 years) at Children's Hospital Boston, randomizing 54 to ondansetron and 53 to placebo. After drug administration, 38 (70%) of the 54 patients in the ondansetron group had complete cessation of vomiting compared with only 27 (51%) of the 53 patients in the placebo group (61% RRR). I found several more randomized trials and meta-analyses are available on PubMed, all of which concluded that use of ondansetron reduced the risk of additional vomiting and the need for intravenous rehydration in the pediatric or adult emergency room setting.Then there is this bit: As noted above, RedHill Biopharma is currently engaged in a Phase 3 clinical trial with Bekinda™ for the treatment of gastroenteritis, with data expected during the second half of 2016. This is a one-to-one randomized trial in 320 patients. My search of PubMed suggests a 42% ± 7% chance a patient in the placebo group will have vomiting, and that the Bekinda™ group should come in only around 22% ± 8%. Assuming 80% power to detect a statistical difference among the two groups, I see the GUARD study as highly likely to achieve its primary endpoint. Below is a snapshot of two statistical analysis graphs I created by inputting the above variables showing (A) GUARD is over 95% powered at current enrollment and (B) statistical significance at p<0.05 is highly likely based on a range of inputs for proportions using data pulled from the literature.He was right on the money. The placebo group was high and the BEKINDA group came in around 22% (it was 21%) as he anticipated. So those were JN's expectations for this trial, which were met, and he has been very gungho about the potential of BEKINDA in the market.
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Post by JHam on Jun 14, 2017 19:15:30 GMT
Aaaaand this just out from JN: www.bionapinc.com/2017/06/redhill-reports-positive-phase-3-for.htmlPhase 3 Bekinda® Hits!
On June 14, 2017, RedHill reported top-line results from the GUARD study. GUARD was a randomized, double-blind, placebo-controlled Phase 3 study designed to evaluate the efficacy and safety of Bekinda in treating acute gastroenteritis and gastritis. A total of 321 adults and children over the age of 12 were enrolled at 21 medical centers in the U.S. and randomized in a 60:40 ratio to receive either Bekinda 24 mg or placebo, respectively.
In order to qualify for the study, a subject must have vomited at least twice in the preceding 4 hours before presenting to the medical center. The primary endpoint was the proportion of patients without further vomiting, without rescue medication, and who were not given intravenous hydration from 30 minutes post the first dose of the study drug until 24 hours thereafter, compared to placebo. It was a tough endpoint to hit and I expected the number of patients "vomit free" (i.e. the placebo response) to be high.
As it turns out, I was right. On an intent-to-treat (ITT) basis, 53.9% of the placebo subjects achieved the primary endpoint. A high number, no doubt; however, the good thing for RedHill is that 65.8% of the patients on Bekinda achieved the primary endpoint. The results were statistically significant at p=0.03. On a per protocol (PP) basis, 69.5% of patients on Bekinda achieved the primary endpoint vs. only 54.9% on placebo. The p-value was 0.01.
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Conclusion
I'm pleased to see top-line data from the Phase 3 GUARD study meet the primary endpoint. Although an additional trial in acute gastroenteritis is likely necessary prior to the company seeking U.S. FDA approval, it's an important step in building investors confidence around the story. I'm excited to see the Phase 2 IBS-D data in September 2017. This positive data from GUARD today increases my confidence level in that outcomes.
I think Bekinda is a $400 million drug. I also think there are larger organizations that might be interested in the drug. For example, Allergan is obviously a major player in IBS-D with Linzess and Viberzi. Bekinda, with a different and proven mechanism of action, might be a nice addition to Allergan's portfolio. Likewise, Valeant, a company that RedHill already has a partnership with for Phase 3 ready bowel prep drug, RHB-103, is the other big player in IBS-D with Xifaxan. Prescriptions of Xifaxan are limited due to the potential for antibiotic resistance to develop to the generic formulation, which is an important antibiotic used to combat traveler's diarrhea and C. difficile infection. Bekinda might make an attractive additional to Valeant's IBS portfolio and allow the company to compete more effectively against Allergan.
Other late-stage assets at RedHill, including Phase 3 RHB-104 for Crohn's disease and RHB-105 for H. pylori infection, round out an impressive GI-focused pipeline. RedHill also now promotes two commercial products, Donnatal for IBS and EnteraGam for chronic diarrhea that further strength the core focus on GI and make RedHill an attractive emerging specialty pharma story for long-term investors.
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Post by JHam on Jun 15, 2017 2:59:07 GMT
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Post by JHam on Jun 15, 2017 16:20:23 GMT
I wonder if Sabby is continuing to unload their position, just as they did with ONCS.
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Post by JHam on Jun 15, 2017 16:36:28 GMT
Of course the other big news for today: RedHill Biopharma Announces Confirmatory Phase III Study Initiated with RHB-105 (TALICIA™) for H. pylori Infection
Subject to a successful outcome and any additional regulatory feedback, the confirmatory Phase III study (ERADICATE Hp 2) is expected to complete the package required for a potential U.S. NDA for RHB-105, newly branded as TALICIA™
The two-arm, randomized, double-blind, active comparator, confirmatory Phase III study is planned to enroll 444 non-investigated dyspepsia patients with confirmed H. pylori infection in up to 65 clinical sites in the U.S., with a primary endpoint of eradication of H. pylori infection at 42 through 70 days after initiation of treatment The first Phase III study with TALICIA™ (RHB-105) (ERADICATE Hp) successfully demonstrated 89.4% efficacy in eradicating
H. pylori infection (p<0.001), supporting the potential superior efficacy of TALICIA™ (RHB-105) over current standard-of-care (SoC) therapies
TALICIA™ (RHB-105) was granted QIDP designation by the FDA under the GAIN Act, including Fast-Track development, NDA Priority Review and extended U.S. market exclusivity, for a total of eight years
H. pylori bacterial infection is a major cause of chronic gastritis, peptic ulcer disease, gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma and is estimated to affect over half of the adult population worldwide
The World Health Organization (WHO) recently published a global priority list of 12 life-threatening multidrug-resistant bacteria, in which H. pylori infection was classified in group 2 high-priority bacteria for which new treatments are urgently needed
The 2015 global and U.S. market potential for H. pylori eradication therapies at current branded prices, were estimated at approximately $4.83 billion and $1.45 billion, respectively www.redhillbio.com/RedHill/Templates/showpage.asp?DBID=1&LNGID=1&TMID=178&FID=1365&PID=0&IID=5130
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Post by JHam on Jun 16, 2017 2:55:29 GMT
Ouch, got hammered after hours.
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Post by JHam on Jun 16, 2017 3:01:37 GMT
Weird. Down 8.75% AH based on 25 shares in volume.
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Post by tmfbmf on Jun 16, 2017 8:13:02 GMT
Weird. Down 8.75% AH based on 25 shares in volume. When I see that I think some dope is trying to manipulate the price down for their next buy. But it never works. It should open at yesterday's close.
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Post by JHam on Jun 16, 2017 12:11:05 GMT
Weird. Down 8.75% AH based on 25 shares in volume. When I see that I think some dope is trying to manipulate the price down for their next buy. But it never works. It should open at yesterday's close. Yeah, that's what it looks like.
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Post by JHam on Jun 17, 2017 1:50:32 GMT
Well today it was for real, sudden sell off in the last 8 minutes of trading. Closed down 6% at $8.60. Whoever is dumping seems to be doing it very slowly in 100 share lots. That indicates to me that it is more likely an institution liquidating their position, and not insiders dumping and running on leaked RHB-104 trial data. Is that just wishful thinking on my part?
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Post by omstem on Jun 17, 2017 3:52:29 GMT
Hi JHam:
I sure do see the AH volume is pretty high compared to the almost non-existent AH trades for this company. However I am not concerned. I may add a bit more to my position but not at these levels. Once it starts downwards it can go further down and I will wait.
Leaked RHB-104 data may or may not be the reason. Indeed I am looking for pretty good RHB-104 data. The management itself there is a possibility for early termination of the trial if the efficacy is overwhelming. I took it with a pinch of salt anyway. So even if they are not going to terminate the trial early, I am fine and that is not why I invested in this company.
Regarding high Placebo numbers for Bekinda, here is what I am thinking. (I am not a doctor and I am not Clinical trials expert nor am I a professional Statistician). I am just an investor and I see the things in the angle that my mind suggests.
Placebo being high for serious conditions like Cancer etc. could be a concern or surprise too. Placebo being high for vomiting is not surprising. I know myself and I know from my kids too that a "feeling of feeling better because you got something to address your situation" works well in situations like Vomiting, nausea, head aches etc. Again this is just my feeling and as I said before I am not an expert in this area.
I am holding and waiting for additional opportunities. Is $8.60 an opportunity? I don't know.
Good Luck to all.
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Post by tmfbmf on Jun 17, 2017 4:51:16 GMT
Hi JHam: I sure do see the AH volume is pretty high compared to the almost non-existent AH trades for this company. However I am not concerned. I may add a bit more to my position but not at these levels. Once it starts downwards it can go further down and I will wait. Leaked RHB-104 data may or may not be the reason. Indeed I am looking for pretty good RHB-104 data. The management itself there is a possibility for early termination of the trial if the efficacy is overwhelming. I took it with a pinch of salt anyway. So even if they are not going to terminate the trial early, I am fine and that is not why I invested in this company. Regarding high Placebo numbers for Bekinda, here is what I am thinking. (I am not a doctor and I am not Clinical trials expert nor am I a professional Statistician). I am just an investor and I see the things in the angle that my mind suggests. Placebo being high for serious conditions like Cancer etc. could be a concern or surprise too. Placebo being high for vomiting is not surprising. I know myself and I know from my kids too that a "feeling of feeling better because you got something to address your situation" works well in situations like Vomiting, nausea, head aches etc. Again this is just my feeling and as I said before I am not an expert in this area. I am holding and waiting for additional opportunities. Is $8.60 an opportunity? I don't know. Good Luck to all. I agree. The placebo effect could be pretty big for something like this.
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Post by JHam on Jun 18, 2017 3:12:46 GMT
Hi JHam: I sure do see the AH volume is pretty high compared to the almost non-existent AH trades for this company. However I am not concerned. I may add a bit more to my position but not at these levels. Once it starts downwards it can go further down and I will wait. Leaked RHB-104 data may or may not be the reason. Indeed I am looking for pretty good RHB-104 data. The management itself there is a possibility for early termination of the trial if the efficacy is overwhelming. I took it with a pinch of salt anyway. So even if they are not going to terminate the trial early, I am fine and that is not why I invested in this company. Regarding high Placebo numbers for Bekinda, here is what I am thinking. (I am not a doctor and I am not Clinical trials expert nor am I a professional Statistician). I am just an investor and I see the things in the angle that my mind suggests. Placebo being high for serious conditions like Cancer etc. could be a concern or surprise too. Placebo being high for vomiting is not surprising. I know myself and I know from my kids too that a "feeling of feeling better because you got something to address your situation" works well in situations like Vomiting, nausea, head aches etc. Again this is just my feeling and as I said before I am not an expert in this area. I am holding and waiting for additional opportunities. Is $8.60 an opportunity? I don't know. Good Luck to all. I agree omstem. Just to clarify, the "issue" about the high placebo response is with patient vomiting subsiding even without taking Bekinda. Not because they continued to vomit (which I know you know, just wanted to make sure everyone else did). The reason why Jason N anticipated a high response placebo group, was because that is what happened in previous studies: A study by Reeves JJ, et al., 2002 enrolled 172 patients (average age 5.3 years) at Children's Hospital Boston, randomizing 54 to ondansetron and 53 to placebo. After drug administration, 38 (70%) of the 54 patients in the ondansetron group had complete cessation of vomiting compared with only 27 (51%) of the 53 patients in the placebo group (61% RRR). I found several more randomized trials and meta-analyses are available on PubMed, all of which concluded that use of ondansetron reduced the risk of additional vomiting and the need for intravenous rehydration in the pediatric or adult emergency room setting.In short, 51% of the placebo arm had "complete cessation" even without Bekinda. And that is due to the nature of the disease, some patients get better on their own quicker than others. Despite the high placebo arm number Ondansetron is now the most prescribed drug in ERs in America. What gives Bekinda the advantage over Zofran (Ondansetron) is that it is a once-daily formulation, compared to 16 tablets over a several day span with Zofran. If this is still in the $8s next week, I'll be adding more.
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Post by omstem on Jun 18, 2017 21:26:07 GMT
Thank you JHam:
The information you shared about Ondansetron now adds more strength to my belief in Bekinda. This along with Jason N's anticipation before the trial results were out is a further reinforcement.
As you rightly observed, the advantage with Bekinda is its dosage. Longer dosage periods or more doses per day have chances of non-compliance and hence less effective. In that sense Bekinda is superior to the current SoC, especially with kids it is a huge advantage.
Let us see how things unfold in the next few months. The good news is that it won't take years for this stock to be noticed by Wall Street. It will be months.
Good Luck to all.
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Post by JHam on Jun 19, 2017 10:07:07 GMT
RedHill Biopharma to Host Conference Call on Successful Phase III Top-Line Results with BEKINDA(R) for Acute GastroenteritisTEL-AVIV, Israel and RALEIGH, N.C., June 19, 2017 (GLOBE NEWSWIRE) -- RedHill Biopharma Ltd. (NASDAQ:RDHL) (Tel-Aviv Stock Exchange:RDHL) ("RedHill" or the "Company"), a specialty biopharmaceutical company primarily focused on late clinical-stage development and commercialization of proprietary, orally-administered, small molecule drugs for gastrointestinal and inflammatory diseases and cancer, today announced that the Company will host a conference call to review the recently announced successful Phase III GUARD study top-line results with BEKINDA® (RHB-102)1 for acute gastroenteritis and gastritis. RedHill announced last week that the Phase III GUARD study with BEKINDA® 24 mg successfully met its primary endpoint of efficacy in treatment of acute gastroenteritis, and that BEKINDA® was found to be safe and well tolerated in this indication. The conference call and webcast call will be held on Wednesday June 21, 2017 at 8:00 a.m. EDT. The conference call, including a slide presentation, will be broadcasted live and available for replay on the Company's website, ir.redhillbio.com/events.cfm, for 30 days. Please access the Company's website at least 15 minutes ahead of the conference call to register, download, and install any necessary audio software. Participants who wish to ask questions during the event can do so by telephone. To participate in the conference call, please dial the following numbers 5-10 minutes prior to the start of the call: United States: +1-877-280-1254; International: +1-646-254-3362; and Israel: +972-3-763-0147. The access code for the call is 1536634.
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Post by JHam on Jun 21, 2017 9:33:06 GMT
RedHill Biopharma to Host Conference Call on Successful Phase III Top-Line Results with BEKINDA(R) for Acute GastroenteritisTEL-AVIV, Israel and RALEIGH, N.C., June 19, 2017 (GLOBE NEWSWIRE) -- RedHill Biopharma Ltd. (NASDAQ:RDHL) (Tel-Aviv Stock Exchange:RDHL) ("RedHill" or the "Company"), a specialty biopharmaceutical company primarily focused on late clinical-stage development and commercialization of proprietary, orally-administered, small molecule drugs for gastrointestinal and inflammatory diseases and cancer, today announced that the Company will host a conference call to review the recently announced successful Phase III GUARD study top-line results with BEKINDA® (RHB-102)1 for acute gastroenteritis and gastritis. RedHill announced last week that the Phase III GUARD study with BEKINDA® 24 mg successfully met its primary endpoint of efficacy in treatment of acute gastroenteritis, and that BEKINDA® was found to be safe and well tolerated in this indication. The conference call and webcast call will be held on Wednesday June 21, 2017 at 8:00 a.m. EDT. The conference call, including a slide presentation, will be broadcasted live and available for replay on the Company's website, ir.redhillbio.com/events.cfm, for 30 days. Please access the Company's website at least 15 minutes ahead of the conference call to register, download, and install any necessary audio software. Participants who wish to ask questions during the event can do so by telephone. To participate in the conference call, please dial the following numbers 5-10 minutes prior to the start of the call: United States: +1-877-280-1254; International: +1-646-254-3362; and Israel: +972-3-763-0147. The access code for the call is 1536634. Just a reminder that the Bekinda CC is today at 9am est. I am only going to be able to catch the very end of it. Curious to hear their thoughts on the likelihood of a confirmatory trial. I thought for sure they would need to do one at first (still think it is likely), but knowing that the efficacy results matched the results of other ondansetron trials, plus there were no safety issues, there is a sliver of hope.
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Post by JHam on Jun 21, 2017 13:02:58 GMT
Nothing groundbreaking on the call and there was only one question in the Q&A.
A few takeaways:
- The lead investigator was very excited about the data. He said besides the good safety profile and very good efficacy results, the EKG data (part of the safety profile), which was one thing that the FDA has been concerned about, met their (FDA) requirements
- RDHL plans to present the data as is to the FDA ASAP, and should know whether they can file an NDA or need to do another trial in October
- BEKINDA P2 IBS data topline data in September
- RHB-104 P3 Crohns trial safety/efficacy interim data readout to happen mid-year
- $10M burn rate per quarter
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Post by JHam on Jun 22, 2017 2:02:04 GMT
This is from JN in the comments section of his last article. It's in response to a question about the high percentage of placebo responders:
Hi Toscane,
I think it is likely the company will need to conduct another P3 trial. Management needs to speak with the U.S. FDA about this. Perhaps the next trial will have a different endpoint that will mitigate the high placebo response rate. The endpoint was very tough to hit. If you read above you see that to qualify a patient must have vomited "at least" twice before getting the drug and that the endpoint was "no more vomiting or rescue medication". For ~50% of the population, a placebo (i.e. no medication) was enough to achieve this endpoint because the disease itself is mostly self-limiting. However, even in the face of this difficult endpoint, Bekinda was superior. Perhaps the next P3 the enrollment criteria will be easier - perhaps only one previous vomit or perhaps no placebo at all. Instead perhaps Bekinda vs. generic ondansetron. I do not know. I'm just speculating, but these are things the company will talk with the FDA about probably in the Q4 2017 or Q1 2018. We will learn more on June 21st. Thanks, Jason
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Post by JHam on Jun 30, 2017 2:40:58 GMT
At the 52 week low. Biotechs got slaughtered today across the board, plus I still think an institution is slowly divesting. This one is becoming a potentially good value play, imo.
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