I have lost two close family members to Covid19, both my parents were hospitalized for over a week in April 2021, my son had Covid19 in October 2020, and more than 65 others in my family and close friends have had it at some time or the other, so I too am affected by this once-in-a-century pandemic. But I am a realistic person who studies facts and data before reaching conclusions.
A piece of recent good news is that the DGCI (Drugs Controller General of India) approved a new oral drug that promises to reduce hospitalisation time and Oxygen dependency for moderate to severe Covid19 cases. The 2-DG (2-deoxy-D-glucose) drug developed by INMAS (Institute of Nuclear Medicine and Allied Sciences), a part of DRDO (Defence Research and Development Organisation), in partnership with leading pharma company Dr Reddy’s Laboratories (DRL) has proved to be effective in clinical trials conducted on 330 patients across 27 hospitals.
The first 10,000 doses will be available on 17th May. Mass production is planned from June 2021 onwards. The drug comes in powder form in a sachet and is taken orally by dissolving in water, much like dozens of ‘gas’ medicines which are very popular in India. Work on the drug had started back in April 2020.
DRDO took the initiative of developing the anti–Covid therapeutic application of the 2-DG drug. In April 2020, during the first wave, INMAS–DRDO scientists conducted laboratory experiments with the help of CCMB (Centre for Cellular and Molecular Biology), Hyderabad and found that this molecule works effectively against the SARS-CoV-2 virus (Coronavirus) and inhibits the viral growth. Based on these results, CDSCO (Central Drugs Standard Control Organization) permitted Phase-II clinical trial of 2-DG in Covid19 patients in May 2020.
The DRDO, along with DRL, started the clinical trials to test the safety and efficacy of the drug in Covid19 patients. In Phase-II trials conducted on 110 patients from May to October 2020, the drug was found to be safe in Covid19 patients and showed significant improvement in their recovery. Phase IIa was conducted in six hospitals and Phase IIb (dose ranging) clinical trial was conducted at 11 hospitals all over India.
Patients treated with 2-DG showed faster symptomatic cure than Standard of Care (SoC) on various endpoints. A significantly favourable trend (2½ days difference) was seen in terms of the median time to achieving normalisation of specific vital signs parameters when compared to SoC.
Based on successful results, the DCGI (Drugs Controller General of India) permitted Phase-III clinical trials in November 2020, which were conducted on 220 patients from December 2020 to March 2021 at 27 Covid19 hospitals in 10 states spread across India. The detailed data of phase-III clinical trial was presented to the DCGI. Significantly higher proportion of patients improved symptomatically and became free from supplemental Oxygen dependence (42% vs 31%) by Day–3 in comparison to SoC, indicating an early relief from Oxygen therapy/dependence. A similar trend was observed in patients aged over 65.
On 1st May 2021, the DCGI granted permission for Emergency Use of 2-DG as adjunct therapy in moderate to severe Covid19 patients. Being a generic molecule and analogue of glucose, it can be easily produced and made available in plenty in the country.
The man behind this discovery is said to be Dr Anil Kumar Mishra, M.Sc. (Chemistry), Ph.D. His research is mainly based on Molecular Biology and synthesis of organic compounds. He carried out post–doctoral research and worked as a visiting Professor in the USA, France, and Germany. He joined DRDO as a Senior Scientist in 1997. He has also served at the prestigious Max Planck Society for the Advancement of Science, a non-profit association of German research institutes.
Being a mimic of D-Glucose, the 2-DG drug gets easy passage into the cells where the Coronavirus is already present. Glucose breaks down into 2–3 carbon compounds, one of them being pyruvate anion, with release of energy. It is a metabolic process called Glycolysis. It is this energy on which all living organisms survive. The Coronavirus also survives on this energy. Unlike D-Glucose, 2-DG is unfit for Glycolysis. No energy is evolved. Sustaining life becomes difficult and as such, the Coronavirus dies within a week due to want of energy. This drug also lowers the oxygen dependence and reduces the hospital stay of patients. It works as an anti-tumour/anti-cancer drug by the same mechanism.
If it is able to destroy the killer Coronavirus, crores of precious lives will be saved, and it’s going to be one of the greatest inventions of modern times.
The drug comes in powder form in sachet, which is taken orally by dissolving it in water. It accumulates in the virus–infected cells and prevents virus growth by stopping viral synthesis and energy production. Its selective accumulation in virally infected cells makes this drug unique. In simple terms, the principle is “Cheat the Cheater”! Any virus, once inside the body, makes its own copies by cheating our human cells and takes their protein to multiply itself. The brilliant thought process of the scientists at INMAS–DRDO, CCMB, and DRL was simple. For every doubling of the virus cell, it needs energy (glucose). So, the medicine is simply a “Pseudo Glucose” which the multiplying virus intakes but this glucose makes it neutral (unable to multiply). Thus, once the rapid multiplication of the Coronavirus is halted, our own antibodies can readily combat it and overpower it within hours. According to some people, this is simply genius, and we should be proud of Indian scientists!
However, several doctors and scientists have said two very important things: (1) This drug should be only used as a support treatment for Covid19 and not as a primary treatment; and (2) It should be prescribed by doctors based on the patient’s medical condition (oxygen saturation level below 9) and not be allowed to be taken by patients on their own accord. But we all know that maintaining the second guideline will be next to impossible in India, where ‘prescription drugs’ are easily sold by pharmacies without a prescription.
Not surprisingly, the anti-Modi media has already started their negative publicity against the possibly miraculous 2-DG drug.
Within four days of the government’s announcement about the approval of 2-DG, on 12th May, Ronak Borana wrote in The Wire: “The approval for 2-DG is based on poor evidence. 2-DG is a modified glucose molecule that has been found to have some therapeutic value as an anticancer and antiviral agent. Research on 2-DG goes as far back as 1956, although it hasn’t been approved to treat any other diseases yet. It is currently mostly used in diagnostic testing and research-related activities.
The Wire couldn’t find any preprint or peer-reviewed research paper uploaded by the DRDO and DRL team on 2-DG clinical trials vis-à-vis COVID-19. Instead, we had to rely on publicly available information, like a press release – from the Ministry of Defence!”
Well, The Wire may not know that DRDO comes under the Ministry of Defence!!
The anti-Modi news website continued: “In news reports about the 2-DG approval, the most widely used image is from an in vitro study of 2-DG against SARS-CoV-2. In vitro refers to studies performed outside a biological entity – like the human body or humanised mice. Studies conducted inside a biological entity are called in vivo. As it happens, according to one preprint paper, members of the Patanjali Research Institute and others suggested the use of 2-DG last year. It was based, of all things, on a computer simulation. This image shows that cell cultures in a laboratory without 2-DG had more viral plaques – clear spots indicating cell damage by the virus – compared to the ones with 2-DG. These studies were conducted at CCMB, Hyderabad. While these experiments show that 2-DG can inhibit viral growth, they tell us little about its efficacy in humans.
“For example, a study published in August 2020 found that around 90 drugs that had been approved by the US Food and Drug Administration had antiviral activity against SARS-CoV-2 – as did ivermectin, hydrochloroquine, doxycycline, did azithromycin and lopinavir. But none of them has been found to have any meaningful effect in human trials with COVID-19 patients. Based on the results from this in vitro trial, the national drug regulator had approved a phase 2 trial for 2-DG – possibly in May 2020. The Wire couldn’t find entries for any of the trials in the Clinical Trial Registry of India (CTRI). The reason for this discrepancy is unclear; emails to the principal investigators of both studies hadn’t elicited a response at the time of publishing this article. The only phase 2 trial registered for 2-DG involved 40 patients across 12 sites. If the 2-DG trials haven’t been registered, they would be in violation of the ICMR’s ethics guidelines.
“The DRDO and DRL conducted the 2-DG phase 3 trial in 220 patients at 26 sites around the country. However, the CTRI registration of this trial does not mention which parameters the trial researchers plan to measure. For example, the phase 2 registration says that the trial’s primary endpoint – the main objective of the study – would be to measure the improvement of trial participants on a 10-point scale. The secondary endpoint includes around 15 other measurements, like mortality, improvement in symptoms, time spent with supplemental oxygen, etc. So the trial will be deemed to be successful only if the researchers measure a significant positive change on the primary endpoints – which in 2-DG’s case the researchers were marking on the 10-point scale. The CTRI registration of the phase 3 trial, however, doesn’t disclose what the primary endpoints were.”
But didn’t they say that CTRI registration was not done? or maybe I read something wrong in The Wire article.
The article continues: “According to the press release, in the phase 3 trial, the participants who got 2-DG had better ‘symptom improvement’ and spent less time receiving supplemental oxygen. But since we don’t know if these two parameters were primary endpoints of the phase 3 trial or just one of the many secondary endpoints, we can’t know if the trial was a success or if the release is only reporting the trial’s favourable findings. For phase 2, the press release says the researchers reported a “significantly favourable trend”: that the vital signs of those who received 2-DG returned to ‘normal’ 2.5 days sooner on average versus those who didn’t receive 2-DG. (We don’t know what is ‘normal’ here either.) There are two problems here. First, normalisation of vital signs is one of the 15 secondary endpoints – not a primary endpoint. There is no information in the release about the primary endpoint nor the other 14 secondary endpoints.”
So as per The Wire, normalisation of vital signs are not important??? I am neither a doctor nor a scientist, but as a son of two parents who were both hospitalised due to Covid19, and my mother’s only brother who unfortunately did not survive, I would say that it is damn important.
The scientific genius website continues: “Second, the word ‘significantly favourable’ and ‘significantly higher’ have been used to describe the results of the phase 2 and 3 results. The phrase ‘statistically significant’ can’t be a throwaway term. To be statistically significant means a particular measurement is too large to be the result of chance. And to claim a result is significant in this way, researchers typically perform specific statistical calculations to prove their point. Without seeing these calculations, it’s impossible to say if the use of the term ‘significantly’ in the press release alludes to significance of the statistical variety or the propagandist one. The press release also doesn’t use the word ‘statistically’.”
Are we more worried about the correctness of the English language of the poor guy who wrote the press release or about the efficacy of the drug itself? Maybe The Wire would have been convinced if Shashi Tharoor wrote the press release.
The article goes on to say: “Further, the DCGI relies on the recommendation of the Subject Expert Committee (SEC), a group of independent experts, to grant COVID-related approval. On October 29, 2020, the SEC asked DRL to add ‘mortality at 28 days’ as one of the efficacy endpoints in the phase 3 trial. But while the press release says the drug was found to be efficacious in the phase 3 trial, it doesn’t say anything about the mortality endpoint. Next, a drug’s efficacy is only as good as its safety profile. While there have been several human trials for 2-DG over the years, the drug hasn’t been approved for human use before this month. According to the CTRI entries, 2-DG’s dosage in its phase 2 trial was 45 mg per kg of body weight in the morning and 18 mg/kg in the evening. But in phase 3, this was increased to 45 mg/kg in the morning and 45 mg/kg in the evening – for a total of 90 mg/kg per day. A smaller study by researchers in the US, published in September 2010, tested the drug’s effects among 12 cancer patients. They found that 60 mg/kg of 2-DG per day was shown to cause QT prolongation – a severe cardiac condition … that can render the heart beat chaotic in some people. This arrhythmia can in turn lead to a sudden cardiac arrest.”
So The Wire thinks that the DGCI, INMAS–DRDO, DRL, CCMB, and the Modi government have come together to give lakhs (maybe crores) of Indians a heart attack?
The article continues: “Another study, published in December 2012, found that ingesting 63-88 mg/kg of 2-DG per day could, among other things, increase the person’s blood sugar levels. The press release also doesn’t say anything about the drug’s safety profile, as ascertained in the phase 2 or phase 3 trials. Phase 3 trials in particular are crucial to understanding any drug’s or vaccine’s long-term safety. (This is one of the reasons the DCGI’s approval for Covaxin without any data from its phase 3 trial proved so controversial.) And of course, it’s impossible to discover any rare side-effects in a trial with only 220 participants; tens of thousands had to have been enrolled instead.”
More than 1,85,30,000 (1.853 crore) doses of Covaxin have already been administered over a period of four months—does The Wire have a count of how many of those people died due to the vaccine?
“There is minimal information about how the trials were conducted, as there is no data or publication in the public domain. This is not a new or proprietary molecule, and this is publicly funded research. The data should be in the public domain,” said Dr Sahaj Rathi of the Institute of Liver and Biliary Sciences, Delhi.
This is the only point that I personally agree with and had sent out this tweet about six hours before I read The Wire article.
Though he has a strong pro-Modi/BJP bias, I am not surprised that Arnab Goswami of Republic TV calls this website “The Liar”.
On another note, the government needs to tell the Intelligence Bureau or the National Investigation Authority or the CBI to investigate whether any funding comes to The Wire from any of India’s enemies/rivals such as China, Pakistan, or the USA’s CIA-funded ‘think-tanks’.
DISCLAIMER: This article reflects author’s view point. Goa Chronicle may or may not subscribe to views of the author