Last month, an announcement by Iran’s news agencies on the successful treatment of COVID-19 patients appears to have slipped beneath the radar. Unusually, contrary to customary reporting, the names of the drugs and the treatment were withheld. Has Iran found a possible cure for COVID-19? Dr James Freeman investigates.
For those of you who like executive summaries, here it is.
Iranian reports on success of clinical trials but details scanty
It may surprise you to know that doctors in Iran have commenced 109 clinical trials on treatments for COVID-19 and recently announced that
“Antiviral drugs have been successfully tested on critically ill patients with COVID-19 by the Infectious Diseases Department of Abadan University of Medical Science.”
The cure looks like no ICU deaths and rapid recovery for patients. While Iran has not announced the name of the drug, it can be accurately deduced via an analysis of their clinical trials database. The drug is a locally produced fixed dose combination of Sofosbuvir (Sovaldi) and Daclastasvir (Daklinza) which is normally used to treat Hepatitis C virus. In what I personally consider a staggering oversight, doctors in developed countries are not testing this combination. It has been right under our noses the whole time and we have left it to Iran to prove it works.
So, which are the possible anti-viral drugs used in the trials?
What follows gets a little technical for a moment then moves on to some Sherlock Holmes-style investigation and a call for action to duplicate the trials in Iran to see if their observations hold true.
Keeping in mind that both Hepatitis C (HCV) and SARS-CoV-2 are +ve sense RNA viruses (which means quite similar, in plain English) it would be reasonable to assume that nucleotide analogues (NUCs) proven to work for HCV might work on SARS-CoV-2. In simple terms, NUCs are fake letters in the RNA genetic alphabet CGAU.
Ribavirin, Remdesvir and Sofosbuvir are all NUCs and represent fake letters “G”, “A” and “U” respectively. The strategy of using fake genetic letters to impair the activity of critical viral polymerases (the thing that clones the genetic material) is well known and will not be discussed further.
With Hepatitis C, we can observe Ribavirin is weak with a log kill of only 0.5 (2/3 viruses killed) and a wide range of well-known side effects because it is not very selective. Conversely, Sofosbuvir is very potent with a log kill of 4.5 (31999/32000 viruses killed). Besides staggering potency, the key feature of Sofosbuvir is its lack of toxicity. Almost every other NUC developed for HCV, HIV and other viruses failed, not due to a lack of potency, but rather due to toxicity on human cells.
While there are high hopes for a Gilead drug called Remdesvir, the reality is that Remdesvir is intravenous only and currently only exists at experimental scale, so, even if it is proven to work, the likely global utility is small unless you are super rich.
Conversely, Sofosbuvir is a tablet and widely deployed making it a superior trials candidate on those grounds alone. We know Sofosbuvir is safe in humans, we know the doses, so why are we not testing it? We did, in fact, consider testing it way back in February but for reasons that elude me that avenue of investigation appears to simply evaporate.
Fortunately, some people are testing it in humans, and the results appear very encouraging.
Report by Tabnak news site on 26 March 2020
In an article published by one of Iran’s top news sites, Tabnak, on 26 March 2020, titled ‘Abadan Protocol in the Treatment of COVID-19′ (in Persian), we see a news report, which translated to English reads as follows:
“Abadan Protocol in the Treatment of COVID-19
Today, Iranian news agencies reported the success of a new treatment in Abadan that has been effective in improving patients with COVID-19. But unlike the usual procedure, no explanation has been given about the details of the treatment.
”In this study, the effect of an antiviral drug on critically ill patients with COVID-19 was examined at Ayatollah Taleghani Hospital in Abadan,” said Dr. Salmanzadeh, head of the Abadan School of Medical Sciences.
Dr. Sara Mubarak, the faculty’s vice chancellor for education and research, said: “Patients were divided into two groups: the first group received the national standard protocol and the second group received the proposed Abadan protocol, and the result was zero. “The group has also declined.”
“It was very important that the people who were in the intensive care unit and received artificial respiration return to normal breathing after four days and get the conditions for discharge from the hospital,” Mubarak added.
Due to the unknown type of treatment, we asked one of the members of the treatment team for this research. He also insisted on not naming the drug used, citing the possibility of individuals and patients invading pharmacies to supply and use it arbitrarily, adding that “we have left the Ministry of Health to confirm the results of the study and the introduction of the drug.”
“According to the national protocol, hydroxychloroquine is in the treatment and only one antivirus has been added to the protocol,” he said in a brief description of the treatment.
“The new protocol was prescribed to 30 patients and compared with 30 patients in the control group compared to the national protocol after one month,” the researcher said of the study groups.
The doctor of Taleghani Hospital in Abadan also said about the results: “Despite the fact that the patients were in a bad mood, no deaths were observed in them and they also had a speedy recovery. Five patients who were intubated were all extubated.” [ie patients on ventilators were taken off them]
A longer version of this press release was published by the Islamic Republic News Agency here and sheds more light on the clinical impact of the Abadan protocol as well as a relevant fact, namely that ethics approval for a clinical trial was sought. That allows us to find the trial. The report selected for translation above was used to shed some light on the secrecy around this.
Explanatory notes on what drug(s) correspond to the mysterious “one antivirus”
Below are some brief explanatory notes that shed some light on what drug(s) correspond to the mysterious “one antivirus” mentioned in this rather intriguing Iranian news report.
- In Iran, Sofosbuvir/Daclatasvir is available as a locally manufactured single-pill fixed-dose combination under the name Sovodak.
- There are a total of 109 clinical trials for COVID-19 registered in Iran with 5 trials of Sofosbuvir/Daclatasvir, one each for Sofosbuvir/Velpatasvir and Sofosbuvir alone, and 102 others researching various therapies.
- A trial of Sofosbuvir/Daclatasvir for COVID-19 in Abadan, for 60 patients (30 controls, 30 treatment) — is listed on the Iranian Clinical Trials Registry and the responsible person listed is Sara Mubarak as mentioned in the news story.
- There are 4 COVID-19 trials registered as being in progress in Abadan, so with N-acetylcysteine, Vitamin D, Vitamin C and Naproxen not being recognised as antiviral medications the only candidate trial that fits the mystery description of “one antiviral” is the Sofosbuvir/Daclatasvir trial noted above.
- An astute observer will note this trial corresponds to the time the death rate in Iran started to fall and further note the Abadan trial has recently been updated with a comment: “Adding other hospitals for recruiting patients”.
- Although relations between many nations and Iran are frosty, their medical system is first class and their clinical trial system stringent, so it seems unwise to simply ignore or discount their observations.
With respect to Daclatasvir, we know it is easy to make, in the Medicines Patent Pool, and currently widely deployed. It is broad-spectrum on Hepatitis C (working for all genotypes) and has very few side effects. It was predicted by South Korean rational drug designers to be active against SARS-CoV-2 back at the end of January but to the best of my knowledge, is not being tested outside of Iran although trials are scheduled to start in Algeria and Uruguay soon.
As a generic, Daclatasvir costs about $0.50 a tablet so could treat patients in bulk at an affordable price. It has a simple 4-step synthesis making it trivial to manufacture at mass scale if existing stocks exhaust as they have done for Kaletra (an HIV drug being repurposed for COVID-19).
As a single agent, virological breakthrough is not observed for 6-8 weeks which, if it turns out to be more important than Sofosbuvir in the Abadan protocol, appears adequate for the short term requirements of treating acute COVID-19.
Because the drug used in the Abadan protocol is a fixed-dose combination, it is unclear if the efficacy observed relates to only one, or both components.
Urgent further investigation seems warranted, so my call to action is for researchers worldwide to add this seemingly proven combination to the array of medications we are looking to re-purpose. It would, I think, be sad if a cure was right under our noses but we refused to research/use it because Iran found it first. While these results suggest the cure we’ve all been hoping for may, in fact, exist, we need to urgently independently revalidate these trials across the world. To aid that, any researcher who wants Sofosbuvir/Daclatasvir to trial against COVID-19, is welcome to contact the author who will provide the medication free-of-charge on the sole proviso that the results, good are bad, are published.
It is a matter of public record that I have facilitated patient access to Sofosbuvir and Daclatasvir as well as other HIV, HBV and HCV medications for the last five years and have made margins from that, as follows:
- I’ve run that enterprise as a not for profit/not for loss and retain the same $100k working capital float today as we started with.
- Those margins have been spent on free treatment, re-treatment, bioequivalence trials, and paying for the preparation of generics related articles.
- I still have a mortgage and drive the same now 10-year-old Subaru.
- Broad government purchases and compulsory licences would destroy that business, if that is how you choose to look at it, as surely as it might damage the Gilead HCV franchise.
- FixHepC.com and FixHIV.com com were deleted off the Internet when I dared to publish the Italian observations that 73% of all the deaths were occurring in patients taking the ACE Inhibitor and ARB class of antihypertensive so those businesses have already been sacrificed on the altar of truth.
- As stated above, I will provide Sofosbuvir/Daclatasvir free to any researcher who can get ethics to independently research this on the single proviso that the results — good, bad or indifferent are promptly published.
Every single drug that is being trialed for this disease has been repurposed and entered those trials with next-to-no evidence they would work. We are talking about Kaletra, Hydroxychloroquine, Azithromycin, Remdesivir, and others. The quickest way to a cure is to find an existing approved drug that can be repurposed because it not only works for it’s approved purpose, but, it also works to fight COVID-19. This is the Holy Grail because it will arrive faster than any vaccine can possibly arrive. The good thing about these drugs is that they are already in pharmacies and can be deployed quickly once solid evidence is available and has been independently validated.
July 11, 2020: Report in the Financial Times, July 10, 2020: A combination of antiviral drugs used to cure millions of Hepatitis C patients has shown promising results as a Covid-19 treatment in hospital trials in Iran. In results from three trials, 94 per cent of hospitalised patients taking a combination of sofosbuvir and daclatasvir showed reduced fevers and improved breathing versus 70 per cent in the control arm. The death rate for those given the drugs was just 5 per cent compared with 20 per cent for those who were not. Anthony Fauci, the head of the US National Institute of Allergy and Infectious Diseases and a member of the coronavirus task force, told reporters the results were “really quite interesting and provocative and encouraging”. See full article here: Fin Times Hepatitis C drugs help combat Covid-19 in trials _ Financial Times