Derek Lowe's commentary on drug discovery and the pharma industry. An editorially independent blog from the publishers of Science Translational Medicine. All content is Dereks own, and he does not in any way speak for his employer.
Lets circle back to remdesivir. We already have the results of the remdesivir Phase II trial that led to its Emergency Use Authorization by the FDA. But now come the first Phase III results, and its safe to say that theyre not making anyone happier. The news isnt bad, but you cant say its particularly good, either.
This was an open-label randomized trial comparing a 5-day course of the drug with a 10-day course. Its important to note up front that there was no control standard-of-care group, which makes interpretation of efficacy impossible it pretty muchalways makes such interpretation impossible (with real-world effect sizes, anyway), which is why you probably shouldnt run uncontrolled trials unless there seems to be no good alternative. And in this case, the trial was run (earlier this year) in this fashion partly because there were no matched placebo vials available and because getting people out of the hospital and making space for new patients was a priority. There are no viral load figures available, either, because of the variability in the testing (and testing capacity) across the different trial sites at the time.
Using data from about 200 patients in each group, there appeared to be no statistically significant difference in outcomes between 5-day and 10-day treatment. These outcomes include relatively easier-to-measure things like time to improvement, clinical status at day 14 after treatment, recovery and hospital discharge, death, and so on. If you want to talk nonsignificant trends, then the 5-day course of treatment actually looked a bit better, but there are possible reasons for that: more males in the 10-day group and more patients on the more severe end of the disease. So I wouldnt say that 5-day treatment is superior, but this study does point to 10-day treatment not being superior.
This means that (to date) we have only two controlled clinical studies of the drug (The early compassionate use reportwas uncontrolled and at this point really adds nothing to our understanding). Theres the one in China that was stopped early due to declining enrollment, and that one did not show any difference between the treatment and placebo groups. But the problem is, given the number of patients it ended up with, it wasnt even powered to show such a difference. Then theres the NIAID study, the first link in the first paragraph above, which found that 10-day treatment was superior to placebo when you measure for time-to-recovery. The authors of this new paper suggest that their results could mean that a 5-day treatment might then show the same thing (which would have the side benefit of not using up so much remdesivir).
But this work just underscores something that I wish that the general public would take on board: remdesivir is not a cure. Not even close. We dont have a cure for this disease yet. Remdesivir appears to be better than nothing if I or someone I knew were in the hospital with the coronavirus, I would expect it as standard of care, and be glad that it was available, but I would not expect it to do anything dramatic. It appears to get people out of the hospital faster a bit faster compared to people who dont get it. No bad thing, not at all, but not what we all want from a therapy, either. I would also definitely consider famotidine. Its not that we have a lot of solid efficacy data yet, but there is some reason to believe that it helps, and it has an excellent safety profile so on balance Id say go ahead. You take what you can get, and right now I think thats pretty much what we can get.
Just this morning, though, comes word of another potential therapy for patients who are in trouble with the cytokine storm immune response. In late April we had some early data from France that the anti IL-6 antibody tocilizumab might help with that situation, but now there are some more solid numbers. This is from the University of Michigan system, a controlled observational study with 154 intubated patients, 78 of whom received tocilizumab. It has to be said that the treatment group was slightly younger and slightly less likely to have underlying pulmonary disease, so the results should probably be trimmed down a bit. But the results were good: 45% lower likelihood of death (the preprints Figure 2).The secondary endpoint of the trial was assessment on a 6-point disease severity scale, and the treatment group looks better on that one, too (the preprints Figure 3A)
There are other things to keep in mind, of course. Knocking down IL-6 activity would be expected to increase the risk of infection in general, and so it proved: the treatment group was twice as likely to develop a further lung infection, generally bacterial pneumonia due to S. aureus. Thats not good, but the time to discharge and fatality rates did not really differ between those who came down with this superinfection versus those who didnt (and for that we can thank modern antibiotics since I experienced bacterial pneumonia personally a few years ago, I am very mindful of them!) So this course of therapy is not without complications, but in the end, it definitely appears to have a real benefit.
The hope, then, is that early remdesivir treatment might decrease a patients chances of ending up in such bad shape to start with, and that tocilizumab might be the thing to give if things head that way. As with all these bimodal treatment regimes, figuring out when to switch gears will be crucial. But its very good to see that theres something we can do about the cytokine storm, and I look forward to more studies of this kind reading out.
Looking for something even better, are you? Who isnt? In the next post (probably tomorrow) well look at the latest news on the things that are really going to get us out of this mess: antibodies and vaccines.
Continue reading here:
Coronavirus Therapy Update (Remdesivir and Tocilizumab) - Science Magazine
- Bio Identical Hormone replacement therapy "alternative medicine" OMT - June 1st, 2010 [June 1st, 2010]
- Healthbeat - Hormone Replacement Therapy - August 5th, 2010 [August 5th, 2010]
- Does Hormone Replacement Therapy increase breast cancer risks? - August 11th, 2010 [August 11th, 2010]
- Hormone replacement therapy increases risk of cancer - October 20th, 2010 [October 20th, 2010]
- Hormone Replacement Therapy Risky For Women - October 20th, 2010 [October 20th, 2010]
- Can Hormone Replacement Therapy Lead To Breast Cancer? - January 31st, 2011 [January 31st, 2011]
- Women Turning To Holistic Hormone Replacement Therapy - February 18th, 2011 [February 18th, 2011]
- Is Hormone Replacement Therapy Dangerous? - March 17th, 2011 [March 17th, 2011]
- Hormone Replacement Therapy Complications - May 8th, 2011 [May 8th, 2011]
- Hormone Replacement Therapy - May 10th, 2011 [May 10th, 2011]
- The New Growth Hormone Replacement Therapy - John Crisler, DO - May 13th, 2011 [May 13th, 2011]
- Suzanne Somers on hormone therapy for menopause, part 2 of 6 - May 20th, 2011 [May 20th, 2011]
- Symptoms of Menopause (Menopause #2) - May 20th, 2011 [May 20th, 2011]
- How to Relieve Menopause Symptoms : Hormonal Replacement Therapy for Menopause - May 20th, 2011 [May 20th, 2011]
- HRT - Hormone Replacement Therapy - May 20th, 2011 [May 20th, 2011]
- What is hormone replacement therapy? - May 20th, 2011 [May 20th, 2011]
- Hormone Replacement Therapy and Breast Cancer - May 20th, 2011 [May 20th, 2011]
- Natural Treatments Instead of Hormone Replacement Therapy - May 20th, 2011 [May 20th, 2011]
- Suzanne Somers on hormone therapy for menopause, part 1 of 6 - May 23rd, 2011 [May 23rd, 2011]
- Hormone Replacement Therapy for post-menopausal women - June 19th, 2011 [June 19th, 2011]
- Joe Rogan talking about hormone replacement therapy 6-14-2011 - June 25th, 2011 [June 25th, 2011]
- Hormone Replacement Therapy and Weight - June 25th, 2011 [June 25th, 2011]
- HRC Hormone Replacement Therapy - June 25th, 2011 [June 25th, 2011]
- Study Hormone Replacement Therapy Increases Breast Cancer Risk - kdka.com - June 25th, 2011 [June 25th, 2011]
- 020 - Neo Hormones - July 1st, 2011 [July 1st, 2011]
- Making Sense of Hormone Replacement Therapy - July 28th, 2011 [July 28th, 2011]
- HRT MTF Transition Report Week 10 - July 29th, 2011 [July 29th, 2011]
- Hormone Replacement - Part 2 - July 30th, 2011 [July 30th, 2011]
- Hormone Replacement - Part 1 - July 30th, 2011 [July 30th, 2011]
- Goldie Lookin Chain - HRT - August 9th, 2011 [August 9th, 2011]
- Natural Hormone Replacement Therapy - September 23rd, 2011 [September 23rd, 2011]
- Testosterone Replacement Therapy (TRT): Optimizing Clinical Outcomes - Michael Aziz, MD - September 24th, 2011 [September 24th, 2011]
- Thyroid Replacement Therapy - Ronald Rothenberg, MD - September 24th, 2011 [September 24th, 2011]
- Dr. Ralph Turner discusses Hormone Replacement Therapy. - September 24th, 2011 [September 24th, 2011]
- 1 year on HRT - September 24th, 2011 [September 24th, 2011]
- The Wiley Protocol - September 24th, 2011 [September 24th, 2011]
- My Journal with Low Testosterone TRT Replacement Therapy - September 24th, 2011 [September 24th, 2011]
- 12 years of HRT: My Transition in photos - September 24th, 2011 [September 24th, 2011]
- Dr. Steven Jepson talks about Bio-identical Hormone Replacment Therapy - September 25th, 2011 [September 25th, 2011]
- Estradiol Valerate Injection HRT (Part 3)of(3) - September 25th, 2011 [September 25th, 2011]
- Study: Post-Menopausal Hormone Therapy Increases Cancer Risk - September 25th, 2011 [September 25th, 2011]
- Bio-identical Hormone Replacement (anti-aging) Therapy - Westchase, Tampa, Florida - September 25th, 2011 [September 25th, 2011]
- natural hormone replacement - September 28th, 2011 [September 28th, 2011]
- 6 Month Hormone Effects (before and after) - September 28th, 2011 [September 28th, 2011]
- Jeff Life, MD - Cenegenics, Hormone Replacement Therapy - September 29th, 2011 [September 29th, 2011]
- Huge - September 30th, 2011 [September 30th, 2011]
- Transsexual hormones,Intramuscular injection, Progynon Depot,Estradiol - October 2nd, 2011 [October 2nd, 2011]
- Dr Whiting on Menopause and the Dangers of HRT - October 12th, 2011 [October 12th, 2011]
- Ahuviya Harel (ADF-Fuensalida) to Start Hormone Replacement Therapy - October 13th, 2011 [October 13th, 2011]
- Clomid Defined - Video - October 14th, 2011 [October 14th, 2011]
- Thyroid Hormone Replacement Therapy - Dr. Denis Rebic - Video - October 14th, 2011 [October 14th, 2011]
- Hormone Replacement Therapy - Video - October 14th, 2011 [October 14th, 2011]
- Dr. Pamela Smith - Bio-Identical Hormone Replacement - Video - October 15th, 2011 [October 15th, 2011]
- Jasper Carrott - Traffic - October 22nd, 2011 [October 22nd, 2011]
- VIDEO: Breast Cancer, Hormone Replacement Therapy Connection - Video - October 24th, 2011 [October 24th, 2011]
- Menopause and Hormone Replacement Therapy with Dr. Sulak - Video - October 24th, 2011 [October 24th, 2011]
- Menopause - October 24th, 2011 [October 24th, 2011]
- bio identical hormone replacement therapy raleigh durcham chaepl hill north carolina - Video - October 24th, 2011 [October 24th, 2011]
- Endocrine Related Hair Loss, Can Hormone Replacement Therapy Help Treat This? Friedman - Video - October 24th, 2011 [October 24th, 2011]
- Dr. Navarro Discusses Bio Identical Hormone Replacement Therapy - Video - October 24th, 2011 [October 24th, 2011]
- Hormone Replacement Therapy by the Book - Eldred Taylor, MD - Video - October 24th, 2011 [October 24th, 2011]
- Sangeeta Pati, MD, FACOG, discusses Hormone Replacement - Video - October 24th, 2011 [October 24th, 2011]
- Active Center's Dr. Gross Discusses Bio-Identical Hormone Replacement Therapy on NEWS 12 NJ - Video - October 28th, 2011 [October 28th, 2011]
- DALLAS ANTI-AGING MEDICINE BIO-IDENTICAL HORMONE THERAPY - Video - October 29th, 2011 [October 29th, 2011]
- Hormone Replacement Therapy and Menopause in Women - Video - November 8th, 2011 [November 8th, 2011]
- Amberen - Natural HRT Alternative Commercial - Video - November 9th, 2011 [November 9th, 2011]
- The Dangers of HRT - Video - November 11th, 2011 [November 11th, 2011]
- The Benefits and Risks of Male Hormone Replacement Therapy - Video - November 16th, 2011 [November 16th, 2011]
- Natural Menopause Treatment - Herbal HRT Alternative - Video - November 23rd, 2011 [November 23rd, 2011]
- Dr. Ian Thorneycroft - Hormone Replacement Therapy - Video - November 24th, 2011 [November 24th, 2011]
- Sarah,MTF Transgender 3months HRT - Video - November 24th, 2011 [November 24th, 2011]
- 26. ftm 1 month on t - Video - November 24th, 2011 [November 24th, 2011]
- Dr. Quint Jardine - Hormone Replacement Therapy with Pellets - Video - November 24th, 2011 [November 24th, 2011]
- 6 Month Changes MTF HRT - Video - November 24th, 2011 [November 24th, 2011]
- Medical Mondays: Will hormone replacement therapy increase my risk of breast cancer? - Video - December 6th, 2011 [December 6th, 2011]
- HRT EXPERIENCES NOT ALL GOOD - Video - December 8th, 2011 [December 8th, 2011]
- Sarah, MTF transgender 9 months HRT - Video - December 9th, 2011 [December 9th, 2011]
- Full: Effect of Testosterone Replacement Therapy on Prostate Tissue in Men with Late-Onset Hypogonadism (Dramatic Health) - Video - December 10th, 2011 [December 10th, 2011]
- Suzanne Somers on hormone therapy for menopause, part 3 of 6 - Video - December 11th, 2011 [December 11th, 2011]
- 1 Year HRT MTF Transition - Video - December 12th, 2011 [December 12th, 2011]