Latest / 20-Minute Health Talk / Can famotidine — a heartburn drug — treat Covid?

Transcript

Can famotidine — a heartburn drug — treat Covid? · 20-Minute Health Talk

• 0:08
  Host: Welcome back to another bonus episode of 20 Minute Health Talk.
• 0:11
  I'm Rob Hoell.
• 0:12
  Last week, we spoke with
• 0:14
  Dr. Onisis Stefas about treatments available today, right now, for people
• 0:17
  diagnosed with COVID-19.
• 0:19
  He broke these treatments down into three main categories over the
• 0:22
  counterwe, prescription, and in hospital.
• 0:26
  And in this conversation, Dr.
• 0:27
  Stefas walked us through some tips for those with mild cases and how
• 0:30
  to manage symptoms at home.
• 0:32
  Today, we're talking about another over the counter medication
• 0:35
  currently being researched as a potential treatment for COVID.
• 0:37
  And it's important to note right up front that this is not an approved
• 0:41
  treatment, as studies are still ongoing.
• 0:43
  But a phase two trial started right here at the Finestein Institutes
• 0:46
  for Medical Research, Northwell's Research arm, in collaboration with
• 0:50
  Cold Spring Harbor Laboratory, showed some promise.
• 0:53
  Famotidine, also known as Pepcid, is a common over-the-counter drug
• 0:57
  used to treat heartburn.
• 0:59
  But could it also quell the inflammation fueled by COVID-19?
• 1:03
  Our guest today led the team of researchers behind a randomized
• 1:06
  outpatient study published in the journal Gut to test that theory out.
• 1:10
  Dr. Tobias Janowitz is an assistant professor at Cold Spring Harbor Lab
• 1:14
  and an adjunct professor at the Finestein Institutes.
• 1:16
  We sat down with him at the Cold Spring Harbor Lab last month to learn
• 1:19
  more about this innovative study, which set out not only to evaluate
• 1:22
  the effectiveness of high doses of famotidine against COVID, but also to
• 1:27
  test the executability of a fully remote trial.
• 1:30
  [Music playing]
• 1:40
  Dr. Janowitz, welcome to 20 Minutes Health Talk.
• 1:41
  Dr. Janowitz: Thank you very much for having me.
• 1:43
  Host: The results of this phase two trial found that famotidine is not only
• 1:46
  safe and effective at potentially treating COVID-19, but it could also
• 1:50
  open up new avenues of research into treatments and other inflammatory
• 1:53
  diseases.
• 1:54
  Dr. Janowitz, what is the takeaway from these findings and what happens
• 1:57
  next?
• 1:58
  Dr. Janowitz: Yeah, thank you for asking those questions.
• 2:00
  The first specific pharmatodine related result was that we found that
• 2:04
  famotidine may help patients recover sooner as they have sustained
• 2:09
  inflammation because of COVID-19 and to essentially alleviate this
• 2:14
  inflammation early and make patients feel better sooner.
• 2:17
  These are preliminary results.
• 2:19
  This is not a definitive study, and further studies are necessary, but
• 2:23
  we demonstrated this both by looking at patient reported outcome
• 2:26
  measures.
• 2:27
  So asking patients, how do you feel on a daily basis across a spectrum
• 2:30
  of symptoms and tracking how their symptoms resolved and comparing
• 2:36
  that for famotidine and placebo in a blinded manner.
• 2:41
  And we also tracked the inflammation in their blood using specific
• 2:45
  markers of inflammation and seeing how those markers were settling
• 2:49
  down slightly sooner when patients were taking fermotradeen compared
• 2:54
  to when they were taking placebo.
• 2:55
  Host: Right.
• 2:55
  We talk about this as being possible treatments for other
• 2:58
  inflammatory diseases.
• 2:59
  I never realized this, but.
• 3:00
  But is that what heartburn medication does?
• 3:02
  Is that what heartburn does?
• 3:03
  Is it causes inflammation?
• 3:05
  Dr. Janowitz: Yeah.
• 3:05
  So the way by which this medication alleviates the symptoms of
• 3:11
  heartburn is thought to be to lower the proton concentrations, that
• 3:15
  is, causative of the heartburn sensation in the stomach and stomach
• 3:19
  area through blocking a specific receptor that modulates this PH in
• 3:24
  the stomach.
• 3:25
  Mug we and others have found that Famotidine can down regulate the
• 3:31
  signaling within the virus infected cells to produce inflammatory
• 3:36
  cytokines.
• 3:37
  And that's been confirmed now in cell culture and in model systems.
• 3:43
  But also we have seen evidence of that in the clinical study that the
• 3:48
  inflammatory molecules would be reduced in the circulation and the
• 3:52
  signal of the inflammation that radiates out into the organism, into
• 3:56
  the whole body, would be dampened sooner.
• 3:59
  And so we think that Famotidine works by essentially not pushing back
• 4:06
  against the virus, but by helping the body lower the inflammation that
• 4:13
  is a consequence of the virus.
• 4:15
  Host: Right.
• 4:15
  And that was part of the problem that people were having when they had
• 4:19
  trouble breathing.
• 4:20
  Was it because of their lungs were inflamed?
• 4:22
  Dr. Janowitz: You are absolutely correct.
• 4:23
  The sustained inflammation is what makes people unwell and what makes
• 4:28
  them sometimes very unwell.
• 4:31
  It is important to say, though, that we did not study the patients who
• 4:34
  were very unwell in our trial.
• 4:36
  So I cannot comment as to the efficacy or the potential efficacy of
• 4:41
  Farmotidine in the context of severe COVID.
• 4:44
  Host: It's fascinating.
• 4:45
  And I think what's great about this study too, is that you brought
• 4:47
  this study to the patients in their homes.
• 4:50
  Tell us a little bit about how that worked.
• 4:51
  Dr. Janowitz: Yeah, that's a great question and that's a really important
• 4:53
  transferable point of this study.
• 4:55
  What we initially set out for, as you have to imagine, when we planned
• 4:59
  the study, there were no vaccines available, there were no treatments
• 5:02
  available, and this was a very contagious disease with potentially
• 5:05
  grievous outcome to patients.
• 5:07
  So we spent long and hard thinking about how can we deliver a study in
• 5:11
  a safe manner?
• 5:13
  And together with the Feinstein Institute's, northwell Health and Cold
• 5:16
  Spring Harbor, we came up with a paradigm where we would essentially
• 5:20
  enroll patients remotely and then take the study medication and the
• 5:24
  study equipment to their place of residence.
• 5:27
  With overnight delivery after they had consented to participate in the
• 5:30
  trial and then deliver the trial whilst they were in the comfort of
• 5:34
  their own home.
• 5:35
  So, in other words, these patients never had to leave the home, travel
• 5:38
  to the hospital, expose other people on the way to the potentially
• 5:42
  infectious and grievous condition that they were having at that point.
• 5:46
  And so we were able to keep not only them, but also the other people
• 5:50
  safe as we were delivering the study.
• 5:51
  And that was a really important outcome that that was fee feasible to
• 5:56
  deliver a study in that manner.
• 5:58
  Host: Is this a better way to do a study like for.
• 6:00
  People to be more comfortable in a situation where, like you said,
• 6:02
  there's no fear of actually having to travel and come in.
• 6:04
  And also, how would you monitor them while they're doing this at home?
• 6:07
  Dr. Janowitz: Yeah, I think there are strength and weaknesses.
• 6:09
  To be fair to an approach like this, if you had a serious condition,
• 6:13
  you could not just study patients remotely.
• 6:15
  You would have to have them under physician supervision.
• 6:18
  And some trials have to be delivered in the hospital and in the safety
• 6:21
  of the hospital.
• 6:22
  Some drugs are given by infusions.
• 6:24
  Sometimes patients need to be close to an intensive care unit if they
• 6:28
  were to get less well.
• 6:29
  But in certain conditions when perhaps the patient is not quite so
• 6:35
  severely affected and when perhaps the patient would prefer to be at
• 6:40
  home.
• 6:41
  That can be the case in certain infectious conditions.
• 6:43
  But it can also be the case in conditions that make you feel unwell,
• 6:47
  like, for example, progressive cancer, which is something that I think
• 6:51
  a lot about and where we were initially planning to deliver this
• 6:55
  disease paradigm, this trial paradigm, which we then lifted to apply
• 7:00
  it to the COVID situation.
• 7:02
  Host: So getting back to this famotidine trial, how were the patients
• 7:04
  taking the medication?
• 7:06
  Dr. Janowitz: So what we did is we developed with a company way to essentially over
• 7:14
  capsulate the medication so that it was indistinguishable between
• 7:17
  placebo and the treatment.
• 7:19
  They were coming into a wide, large capsule that could be swallowed
• 7:23
  orally, and they would take this medication three times daily, albeit
• 7:27
  at a much higher dose than you would take it over the counter for
• 7:29
  heartburn.
• 7:30
  So we delivered 80 milligrams three times daily as a capsule, and
• 7:35
  rather than 20 milligrams once to twice daily.
• 7:38
  Host: And I think that's what's so fascinating about research and clinical
• 7:41
  trials.
• 7:41
  So many times, when you're looking for one thing, it may unlock
• 7:45
  something else.
• 7:46
  Dr. Janowitz: Yeah, sure.
• 7:46
  There are many examples, especially in my area of expertise, true
• 7:50
  expertise in medical oncology, where initial studies have been
• 7:54
  conducted to find out if a drug works in a certain way, in a certain
• 7:58
  condition.
• 7:58
  And people realize that perhaps that's not the case, but something
• 8:02
  else might be the case.
• 8:03
  And then they can take it back into the laboratory, confirm that
• 8:07
  secondary finding, and then bring it back into clinical trials to
• 8:10
  perhaps make an impact on another condition.
• 8:12
  Host: What was the timeline of the study?
• 8:14
  So we initially had some indication that perhaps patients who were on
• 8:20
  famotidine were doing slightly better.
• 8:22
  And so the first thing that we did, we did a case series, which is
• 8:29
  preliminary clinical research.
• 8:31
  Then we developed this phase two clinical trial, which is a randomized
• 8:35
  placebo control trial.
• 8:36
  So that's a strong study, but with small patient numbers.
• 8:40
  So it's not an efficacy study.
• 8:42
  It looks for ways to how to discover efficacy in further clinical
• 8:47
  trials.
• 8:48
  And that trial was started in July after we published the case series
• 8:55
  July 2020 and the results were published
• 9:00
  Early this year, in 2022.
• 9:03
  I think what is important from my perspective is the other extended
• 9:07
  findings that we learned from the trial, because those we are hoping
• 9:10
  to take forward.
• 9:11
  Host: So when you say take the other findings forward, what do you can you
• 9:14
  expand on that?
• 9:14
  Dr. Janowitz: Yeah, so the things that were really important for us was to
• 9:18
  demonstrate that firstly, a trial could be delivered in this remote,
• 9:23
  decentralized manner.
• 9:25
  So you could imagine this is perhaps transferable.
• 9:27
  Say if you wanted to study a rare condition across the United States
• 9:31
  where you have 300, 400 patients spread over an entire country, and
• 9:35
  you could have a central hub ship out the trial to the patients and
• 9:40
  somebody from Texas, somebody from Maine and somebody from Vermont
• 9:44
  could sort of enroll in this study and be part of the study, and it
• 9:50
  could be safely delivered, perhaps with a central hub where we collect
• 9:54
  data.
• 9:55
  And so that opens up a completely new way to perhaps deliver clinical
• 9:58
  studies and that is worth to explore further.
• 10:02
  The other point is the study was very inclusive and that is one of the
• 10:10
  big challenges of delivering health care, as we are now trying to
• 10:16
  develop new clinical trials and trial paradigms to reach out to
• 10:20
  patients and patient populations who would not normally participate in
• 10:24
  clinical trials so much.
• 10:25
  And we had 33% black African American participants in the study, 25%
• 10:31
  Hispanic patients in our study.
• 10:33
  And we believe that one of the reasons why that was possible was
• 10:37
  because we made it easier for them to enter clinical trials and to
• 10:43
  lower the access barrier because we would take the sort of effort and
• 10:50
  the cost of the clinical trial down by bringing the trial to their own
• 10:56
  home.
• 10:56
  Host: Yeah, I think it's so much easier, right.
• 10:58
  When you're doing something in your home, it's much more easy to be a
• 11:01
  part of that.
• 11:02
  Does that create problems as far as, like, how do you track, how do
• 11:05
  you make sure they're taking their medication?
• 11:07
  How do you know that everything is going to be correct?
• 11:10
  Dr. Janowitz: Yes, of course.
• 11:10
  New paradigms, new problems, new challenges, let's say.
• 11:13
  And these challenges have to be taken one step at a time.
• 11:18
  We were able to follow each patient every day by having a dedicated
• 11:23
  person who would call them up, who would monitor their data that they
• 11:26
  would send in every day.
• 11:27
  With regards to the drug concordance that you're asking about, we
• 11:32
  would tackle that in two fronts.
• 11:34
  One would be to ask the patients on a daily basis, have you taken your
• 11:38
  medication?
• 11:39
  And record their answers.
• 11:41
  The other approach that we took, we took a blood sample and then used
• 11:46
  the facility here at Cold Spring Harbor Laboratory to trace the blood
• 11:49
  and to trace the medication in the blood and thereby be able to
• 11:53
  determine exactly what concentration of the blood of the drug was in
• 11:59
  the blood.
• 12:00
  At any one time.
• 12:01
  Host: So you kind of would know anyway.
• 12:02
  Dr. Janowitz: Correct.
• 12:03
  Host: Do you feel like this type of thing is going to help get more people
• 12:06
  involved in more studies across the board?
• 12:08
  Dr. Janowitz: Absolutely.
• 12:09
  And that's the key point and key message that I think I would like to
• 12:13
  put out here.
• 12:14
  This study is one contributor to shifting the paradigm of how we
• 12:19
  deliver clinical trials.
• 12:21
  We are not the only people to think about this.
• 12:23
  This is a national agenda.
• 12:25
  There are many people who are trying to do the right thing.
• 12:28
  The government is coordinating it in that manner as well.
• 12:31
  And the NIH is encouraging people to think about decentralized trials
• 12:36
  and using remote clinical trial monitoring as an enrichment for
• 12:42
  clinical research.
• 12:43
  I think what is important is we were able to do this, admittedly with
• 12:47
  a small number of patients.
• 12:48
  55 patients were enrolled in the end, but we were able to collect
• 12:52
  their data, deeply, analyze it, write up the results and publish them
• 12:57
  in sort of some total of 18 months from the conception of the study to
• 13:01
  the report of the results.
• 13:02
  And I think that's a really important sort of benchmark and an early
• 13:07
  contribution to delivering this type of clinical study so that others
• 13:12
  can learn from the things that went well and from the challenges that
• 13:16
  we encountered.
• 13:17
  Host: That's great.
• 13:17
  This trial was a collaboration between Finest and institutes for
• 13:20
  medical research, cold Spring Harbor Laboratories.
• 13:23
  And you said this alliance unlocks potential on both sites.
• 13:26
  Can you explain what you mean and how other institutes could benefit
• 13:30
  from this model?
• 13:31
  Dr. Janowitz: Yeah, I can.
• 13:32
  Thank you for asking that, because I think what is really important to
• 13:36
  recognize is as you take on challenges where individual components
• 13:40
  have to be delivered at the highest level, you sometimes have to bring
• 13:44
  partners together that are experienced at the respective components.
• 13:49
  Cold Spring Harbor is a center of excellence for basic research and
• 13:54
  has made fundamental contributions there and has the facilities to
• 13:57
  drive true deep research.
• 14:00
  The Finestines Institutes are a great translational research center
• 14:05
  where patients where some groups work a bit closer to clinical
• 14:09
  research, and some groups work on fundamental research.
• 14:12
  So they have this translational arm bringing research closer to the
• 14:16
  patient and bringing the patient closer to research.
• 14:18
  And Northwell Health is an institute that is extremely strong at
• 14:22
  healthcare delivery and operations.
• 14:24
  And so each component brought their own expertise to the table to
• 14:30
  deliver together a clinical trial that none of them could have
• 14:34
  delivered in isolation.
• 14:35
  So I would go as far as saying not only was this made it the trial
• 14:41
  easier, it was a necessity to bring these three groups together with
• 14:46
  their respective strength in order to be able to deliver this.
• 14:49
  And with regards to what can others learn from this, there are, of
• 14:54
  course, within the United States and within over the globe, other
• 14:58
  centers where.
• 15:00
  Research institutes and clinical entities work closely together.
• 15:04
  But I think it is really important to embrace this partnership of
• 15:08
  fundamental research and clinical excellence as we move science
• 15:12
  forward and as we try to deliver better science for the benefit of
• 15:17
  patients.
• 15:21
  Host: Now more studies are underway building on these findings.
• 15:24
  Among this research search was another phase II trial from the fine
• 15:26
  scene institutes, which showed that famotidine may also influence
• 15:30
  nerve signaling from the body to the brain.
• 15:32
  That paper was published in May in the journal Molecular Medicine.
• 15:36
  And that does it for this bonus episode of 20-Minute Health Talk.
• 15:39
  Thank you to Dr.
• 15:40
  Janowitz, as well as the Feinstein Institutes and Cold Spring Harbor
• 15:44
  researchers, administrators and participants for their work and
• 15:48
  dedication.
• 15:49
  Thanks to you, the listener, for tuning in.
• 15:52
  I'm Rob Hoell, and on behalf of my cohost, Sandra Lindsay, who is
• 15:55
  currently in Jamaica supporting a Northwell led mission trip, a topic
• 15:58
  I'm pretty sure you'll be hearing about very soon in the near future.
• 16:01
  Have a great day and stay safe.