Covid vaccine should not be a hurried affair
As the Covid-19 pandemic rages on and the number of cases remains short of the peak in India and elsewhere in the world, the search for biomedical tools is getting more desperate. Claims about vaccines, new drugs, repurposed old drugs, immune boosting concoctions and so on continue to emerge with rapidity.
Scientists and pharma companies seem to be working at a feverish pace to come up with a magic weapon against the novel coronavirus. Literally, dozens of candidate vaccines are in the pipeline, while some have already reached the stage of human clinical trials. But every announcement of a new vaccine or a new drug is accompanied by a storm of comments, questions, controversies, politics and swings in pharma stocks in the bourses.
The past few days have seen many such announcements in India and elsewhere. First came the ayurvedic ‘cure’ for Covid-19 from Patanjali. Following an uproar over lack of appropriate clinical evidence, Patanjali downgraded claim for its drug from ‘treatment’ to ‘management’ of Covid-19. The vaccine announced by Hyderabad-based Bharat Biotech, along with the Indian Council of Medical Research (ICMR), became a matter of controversy because of the unreasonable timeline for completion of clinical trials fixed by the medical agency. Based on data from the studies in rats, mice and rabbits, the Central Drugs Standard Control Organisation (CDSCO) gave the go-ahead for human clinical trials.
Even before the first volunteer was recruited for the vaccine, a leaked ICMR letter talked of the vaccine being ready for use by August 15. The medical body justified its action by saying its intention was only to fast-track clinical trials. Another headline grabbing announcement came this week from the Bengaluru-based Biocon about a new drug — rather an existing drug repurposed for Covid-19. Based on trials involving 30 patients, the company has claimed repurposing of Itolizumab as a breakthrough. This announcement has also been met with scepticism and more questions.
Before any new drug or vaccine reaches the market, it has to pass through a series of scientific, clinical, regulatory and ethical processes. These mandatory requirements vary from country to country and may take anything, from months to years, to be completed. However, if the regulatory authority is presented with compelling scientific evidence or is convinced about the need to tweak or speed up certain steps, it can do so in times of emergencies or on other grounds.
Drug regulatory authorities globally have been under pressure for fast-tracking such approvals, ever since the occurrence of the pandemics of swine flu, Ebola etc in the past two decades. This can be done in different ways. For instance, safety studies may be shortened if an existing drug (which has undergone such studies and is already in market) is sought to be repurposed for a new disease. While ethical approvals cannot be done away with, some regulators have relaxed conditions under which ethics committees can review applications. For instance, review committees can hold virtual meetings and patient consents can be obtained digitally. Another way could be to allow the use of a drug approved in another country without repeating full-fledged trials.
The point is how much deviation can be allowed from standard procedures, to deal with health emergencies like the present pandemic. It can’t be left to whims or the discretion of individual regulators. There should be some clarity and transparency about regulatory processes followed for fast track approvals. The idea is not to compromise patient safety while tweaking standard protocols in times of emergencies.
Leading medical regulators have evolved new frameworks, like the Coronavirus Treatment Acceleration Program devised by the US Food and Drug Administration and collaborative programme on drugs and vaccine supported by the European Medicines Agency. India is yet to develop such a framework specifically for Covid-19 or for other health emergencies. All that the drug regulator has done is to put on hold all other approvals so that it can focus on Covid-19 related applications for their speedy clearance.
It is in this backdrop that questions have been raised about the approval given to Itolizumab for use in Covid patients based on trial only in 30 patients (20 were given the therapy while 10 were on standard treatment). Itolizumab is an immunomodulator, meaning it treats a disease by modulating the immune system. The drug — which was originally discovered in Cuba — was approved in India in 2013 for treatment of ‘cytokine release syndrome’ in patients of chronic plaque psoriasis. The coronavirus has been seen to cause over-reaction of immune system resulting in the release of a large number of molecules called cytokines which can affect the functioning of lungs and other organs. The company says that the therapy is effective in preventing cytokine release in moderate to severe patients of Covid-19 with acute respiratory distress syndrome or ARDS. Therefore, this therapy can be useful for Covid patients who are on ventilator facing respiratory problems, and cut down mortality. It has been tested in a group of patients in Cuba as well. The results of this trial are awaited.
Besides the small number of patients on which the new drug was tested in two hospitals in Mumbai and Delhi, there is lack of unanimity among experts if ‘cytokine storm’ in Covid-19 patients is large enough to warrant immunomodulation. An editorial published on June 30 in the Journal of American Medical Association (JAMA) noted that available data about cytokine storm being a key factor in Covid-19 patients was weak and that indiscriminate suppression of inflammation could increase the risk of secondary infections. Given the fact that these observations are very recent, the drug regulator and the company should make it clear if such concerns were taken into account. This can be done by subjecting data to peer review.
If any fast-tracking of clinical trial approvals is needed, let’s do it in a transparent and open manner. In no way should it be allowed at the cost of science and safety of those participating in trials.
