Top doctors in key Covid wards are guarded in their reception to the 2-DG (2-deoxy-D-Glucose) drug the Centre launched Monday granting emergency use approval and saying it will reduce recovery time and oxygen dependency for Covid-19 patients.
Their consensus is that the principle behind 2-DG, traditionally used as a cancer drug, is well-established. It inhibits glycolysis, the process by which cells break down glucose which helps viruses get energy to replicate and spread and so disrupting this could be a tool in the treatment of Covid-19. But, they said, they need more clinical trial evidence before it can be widely used.
The promise of 2-DG as a therapeutic tool finds mention in at least five papers, including by German, Brazilian and US scientists published last year, but none draws from testing in actual hospital settings.
The version launched in India, offered by Defence Research and Development Organization (DRDO) with Dr Reddy’s Laboratories (DRL), is linked to a paper written in March 2020 by a team led predominantly by members of Haridwar-based Patanjali Research Institute.
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The non-peer reviewed paper was posted on ResearchGate with the lead author Acharya Balakrishna, chairman, Patanjali Ayurved. This pre-print was cited in the January-February 2021 issue of the Indian Council of Medical Research’s Indian Journal of Medical Research.
His fellow authors include three affiliated with Patanjali Ayurved (Pallavi Thakur; Narsingh Chandra Dev and Anurag Varshney); one from Vivekanand Education Society’s Institute of Technology (Shivam Singh); another from the Jain Vishva Bharati Institute (Viney Jain); and the vice-chancellor of Chennai-based SIMATS, Saveetha Institute of Medical and Technical Sciences, (Rakesh Kumar Sharma). Thakur and Sharma have been associated with DRDO as well. Welcoming the clearance, Sharma tweeted that it was a “matter of great pride” that the research for 2-DG was conducted at SIMATS and Patanjali Research Institute “under the leadership of Balkrishna.”
2DG hasn’t been launched in the market and the price of the sachet hasn’t been announced. Many experts have flagged concerns over the approval.
Records show multiple attempts by DRL in 2020 to seek a speedy approval with truncated trials which were overruled by the Subject Experts Committee, the expert panel of the Indian drug regulator.
The SEC cited lack of sufficient evidence to greenlight such a clearance without adequate human testing. Following a Phase 2 and Phase 3 clinical trial, the regulator granted restricted permission for emergency use on May 1.
Dr Shashank Joshi, expert member in the Maharashtra Covid task force, said that, conceptually, the drug appears attractive but there is not much data in the public domain. “I would only use it in research mode till we have data in the public domain. Studies have not been done in the population of diabetics and those with coronary artery disease. It may be useful in mild to moderate disease after validation in research mode,” Joshi said.
Lok Nayak Jai Prakash Narayan (LNJP) Hospital Director of Medicine and Medical Director Suresh Kumar said that it holds promise. “We will have to see how well it performs once we prescribe this. So far, it is available only in select centres. Once we practically see this, it may work, because oxygen is something which most of the patients require,” he added.
“As things stand, I will not be introducing it as part of treatment. There is many a slip between theoretical value and clinical outcome, and they haven’t shown any significant clinical outcomes. I would be happy if they would do a good Phase 3 clinical trial,” said Sumit Ray, head of critical care at Holy Family Hospital in New Delhi.
It’s paucity of data that experts point to.Flagging the lack of evidence to back claims that 2DG could reduce the need for supplemental oxygen, together with the “lack of transparency” in the approval process, Madhav Thambisetty, neurologist and Adjunct Professor of Neurology at Johns Hopkins, said that there were “serious concerns about scientific rigour yielding to expediency in decision-making that further exploits the growing desperation of patients and their families.”
As per the four available minutes of SEC’s meetings on 2DG, the drug was tested in a Phase 2 proof of concept study, a Phase 2b dose-finding study and Phase 3 clinical trials.
According to a May 8 release by the Ministry of Defence, the drug had been tested on 110 patients in Phase 2 trials. However, this does not reflect in the details uploaded and updated on the trial registry — DRL’s June 2020 listing of this Phase 2 trial mentions a sample size of only 40 participants.
The Phase 3 trial was conducted on 220 patients between December 2020 and March 2021 at 27 Covid hospitals across the country. “The detailed data of (the) Phase-III clinical trial was presented to DCGI,” it stated, adding that the results of the trials indicated “early relief from oxygen therapy/dependence.”
Despite 2-DG receiving authorization on May 1, the Central Drugs Standard Control Organization (CDSCO) is yet to make public the minutes of the SEC meeting where emergency authorization was recommended.
Queries and phone calls to Drug Controller General of India VG Somani remained unanswered.
On May 8, the Ministry of Defence said that a “significantly higher” proportion of Covid-19 patients – 42% — that received 2-DG had improved symptomatically and became free from supplemental oxygen dependence by the third day. In comparison, 31% of those receiving standard of care had seen such improvement. However, no data from the trials has been published.
2-DG has been studied around the world for decades due to its potential benefit in cancer treatment. Realising the effect of 2-DG on non-surgical treatment of cancers and expecting its impact “to be very significant,” the DRDO’s Institute of Nuclear Medicine and Allied Sciences (INMAS) had transferred the technology for this molecule to DRL in 2014.
In its submission for Phase 2 clinical trials with 2DG, the company had said, “While 2DG is not an approved drug, it has been studied in 218 clinical trials for the treatment of various cancers globally. 2-DG has not been evaluated in the acute treatment of moderate to severe COVID-19.” INMAS was responsible for the genesis of this hypothesis and the testing of 2-DG’s efficacy against SARS-CoV-2, it stated.
Messages and phone calls to Dr Sudhir Chandna, Additional Director at DRDO’s INMAS went unanswered. Queries to DRL and DRDO remained unanswered. —(with ENS, Delhi, Pune)
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