This is somewhat true - but its more complex than what you are conveying.
In fact Matt Kaeberlein wrote up a backgrounder on exactly what happened in the phase 3 trial with RTB101 / Mannick trial - and I recommend you read it. The FDA changed the endpoints of the trial between the phase 2 and phase 3 trial - which messed things up. I think (and many geroscientists also believe) that it would have passed if the FDA had not done this.
Also, it should be noted that Matt Kaeberlein was an advisor to ResTORbio, so he had an inside view of the clinical trial. This paper was written after the company had been shut down. I think Matt felt that the full circumstances around the failure needed to be explained to people, and I agree.
See attached paper:
RTB101FailureAnalysis_j.tma.2020.01.002.pdf (367.9 KB)
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You make a valid point. RTB101 is a dual mTOR inhibitor that showed a decrease in respiratory infections reaching statistical significance in phase 2 human trial. It did the same when combined with everolimus. Why the company decided to proceed with it alone, and not in combination with everolimus, isn’t clear. It’s certainly possible that it would have met the endpoints if they had. But once again, the human data is lacking, and it remains speculative.
My fervent hope is that positive human data will start to emerge regarding the prevention of some disease state with low dose intermittent rapa. We’re still not there.
The trial with the quickest possible results would be Dr. Brad Stanfield’s trial where he wants to measure fitness markers in older patients.
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LaraPo
#324
Could you share a link to that on Twitter? I apparently missed it.
zazim
#325
Yes, this is exactly what happened. In the phase 1 and phase 2 trials, anyone that exhibited 2 or more symptoms of an RTI had to go to the lab to be tested to see whether they really had an RTI. In the phase 3 trial, the FDA changed the endpoint to test whether the subjects thought they had an RTI. I think their the reasoning was that what we really care about is how people feel. It was an older population, and they often feel less than well. Of course, they pulled the plug right before Covid. If the endpoint had been something along the lines of reduced risk of hospitalization and death, I’m confident it would have passed readily.
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约瑟夫
#326
FWIW
Carnac the Magnificent*
*Carnac was a “mystic from the East” who could psychically “divine” unknown answers to unseen questions.
I see…
The trial will produce very little results, if any of scientific value. With a reported cost of $400,000, the one positive result, the trial will be quite profitable to some individuals.
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It’s possible that it would have reached significance. Possible.
Here’s a nice overview , and essentially postulates what I’ve already mentioned, that low dose rapa may have benefits related to CD8+ T cells as well as diminished programmed death cells. This could have cancer implications as we age.
We need some kind of human study looking at 5 mg per week of rapa in a healthy population and cancer rates. Use the general population as a control arm. We need to move from theory to clinical evidence in humans.
Immunologic and dose dependent effects of rapamycin and its evolving role in chemoprevention - ScienceDirect
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I personally like Dr. Luongo’s fast mimicking diet. I’m not a fan of “real” fasting, and wouldn’t be doing it at all without his diet. But to each his own.
Those battling cancer may find useful this recent publication by Paul Merik on the use of repurposed generics to fight cancer. As with Rapamycin, there is little incentive for the medical establishment to promote low-cost effective generic treatments. Particularly when the standard chemo/radiation treatments for cancer are so profitable.
https://covid19criticalcare.com/reviews-and-monographs/cancer-care/
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In my opinion, it’s the 5 days of fasting combined with chemo that gets his results. The small amount of food that he recommends (sells) is just a crutch to complete the 5 day session.
Sure it’s a crutch (ie it can’t be any better for your health than a real 5-day water only fast), but it’s still a useful crutch for many who wouldn’t do a fast otherwise.
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A few years ago, I did the 5 day fast for 3 consecutive months, which he recommends in his book. I didn’t use his food, just had a protein bar each day.
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zazim
#334
I am a fan also. I still have three packages left.
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GregE
#335
Dr. GREEN (rapamycintherapy.com) would agree and told me with my prostate cancer (non aggressive) that R will likely slow the spread but neither cure nor stop it. Because it’s use reduces senescent cell conversion by ~30%, it likely is something of a preventative to delay the onset and premature development of cancer.
Having been a smoker, any thing to delay is a win.
Review Dr. SARAH Hallberg’s interview with Dr. PETER Attie on You Tube about how to manage a cancer diagnosis… so not be as she said, ‘a sitting duck’ one you’ve completed your initial cancer treatment!
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Paul
#336
Here is my N=1 data. Was diagnosed with Prostate cancer 3/2014
Rather than get surgery, I researched and settled on metformin and diet. About 4 years ago I added rapamycin.
MRI’s and testing had shown no progression and a Galleri test last month couldn’t detect any cancer.
Even my PSA is at its lowest levels in 11 years.
I take 10 mg every 10 days. Stopped metformin about a year ago and switched to Jardiance 25 mg
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@Paul question for you on managing the 10 day rapa dosing schedule. How do you do it? I’m having a devil of a time shifting my schedule every week. Workouts, meal schedules, etc. Any secrets? Perhaps you don’t worry about those details.
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Paul
#338
I have a large spreadsheet - record about 20 biometrics every morning
so I record when I take rapamycin and its easy to see 10 day increment
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JuanDaw
#339
Periactin for cancer? N = 1.
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The Beatles were heavy smokers. George Harrison died of lung cancer. Paul & Ringo are doing great.
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