Can We Teach an Old Drug New Tricks?

Editor’s Note: This article was published in Pharmaceutical Technology Europe’s May 2020 print issue.

It has been widely reported, perhaps disproportionately due to the attentions of certain key political figures and the media, that there may be the potential for chloroquine and hydroxychloroquine to be used in the treatment of COVID-19 symptoms. However, there is little evidence to support efficacy of the drugs in the treatment of COVID-19, and, in fact, concerns are being raised about potential safety issues relating to the side effects of the therapies.

Serious risks and lacking evidence

Chloroquine and hydroxychloroquine were initially used as prophylaxis and treatment of malaria. More recently, these drugs have also been used in the management of other conditions, such as lupus and rheumatoid arthritis. However, these therapies are known to carry the risk of serious side effects, such as heart rhythm problems, liver and kidney problems, nerve cell damage, and low blood sugar.

In a press release, the European Medicines Agency (EMA) issued a reminder on the risks that are known to be associated with chloroquine and hydroxychloroquine (1). Additionally, the agency stressed that there is a chance the side effects can be exacerbated if these therapies are combined with other medicines, such as azithromycin-an antibiotic that may result in similar side effects on the heart (1).

Many of the studies that support the use of chloroquine and hydroxychloroquine to treat COVID-19 are preprints (not yet subjected to peer-review and/or are not necessarily suitably designed to determine effectiveness), have included only small patient populations, and are methodologically flawed. The French study that piqued interest in using hydroxychloroquine to treat COVID-19, by way of example, was not designed to the expected industry standard and, so despite being published (2), is now undergoing an additional independent peer review (3).

Furthermore, studies demonstrating a contrary opinion-that chloroquine and hydroxychloroquine do not have a suitable risk-to-benefit ratio in terms of COVID-19 treatment-also have limitations. For example, a Brazilian study, which has been posted online as a preprint, has indicated an elevated risk of mortality and arrhythmias when administering a high dose of hydroxychloroquine (4). However, this study did not include a control group, involves simultaneous use of other drugs, includes severely infected patients, and only included a small patient population.

Clear benefits of repurposing

There are clear benefits to following a reformulation/repurposing pathway, particularly when time is of the essence, as is the case for COVID-19. As more expertly discussed in one of this month’s ‘Development’ feature articles, reformulation can give developers a significant ‘head-start’ by minimizing regulatory risk and accelerating speed-to-market. Yet, it is also imperative that there is a benefit, and certainly no compromise, to the patient with the reformulated or repurposed drug.

On a positive note, in the current global pandemic, there are studies underway, that are designed appropriately (randomized, placebo-controlled, double-blind, etc.) and are expected to give more definitive results in terms of safety and efficacy of chloroquine and hydroxychloroquine to treat COVID-19 (5–7). So, to answer the question of whether it is possible to teach old drugs new tricks, then yes, it is possible, but it certainly should not be rushed, and appropriate, robust data should be ascertained to ensure treatment efficacy and patient safety, irrespective of how urgent the situation may be. 

Stay safe and healthy.

References

1. EMA, “COVID-19: Reminder of Risk of Serious Side Effects with Chloroquine and Hydroxychloroquine,” ema.europa.eu, Press Release, 23 April 2020.
2. P. Gautret, et al., Int. J. Antimicrob. Agents, In Press, Available Online 20 March 2020.
3. International Society of Antimicrobial Chemotherapy (ISAC), “Joint ISAC and Elsevier Statement on Gautret et al. Paper [PMID 32205204],” isac.world, Press Release, 11 April 2020.
4. M.G.S. Borba, et al., JAMA Netw. Open, 3 (4.23) e208857 (2020).
5. Bill & Melinda Gates Foundation, “COVID-19 Therapeutics Accelerator Awards $20 Million in Initial Grants to Fund Clinical Trials,” gatesfoundation.org, Press Release, 30 March 2020.
6. Sandoz, “Novartis to Sponsor Large Clinical Trial of Hydroxychloroquine in Hospitalized COVID-19 Patients,” sandoz.com, Press Release, 20 April 2020.
7. University of Oxford, “COPCOV COVID-19 Study Prepares to Begin Participant Enrolment,” tropicalmedicine.ox.ac.uk, Press Release, 23 April 2020. 

Article Details

Pharmaceutical Technology Europe
Vol. 32, No. 5
May 2020
Page: 5

Citation 

When referring to this article, please cite it as F. Thomas, “Can We Teach an Old Drug New Tricks?” Pharmaceutical Technology Europe 32 (5) 2020.