Remdesivir vs Favipiravir drugs for Covid-19
India needs to urgently decide on a course of medicines for Covid-19 treatment. The virus is here to stay, at least in the near-term. A vaccine too, is a while away. There are at least 50 different drugs, from HIV protease inhibitors to anti-virals to ACE inhibitors, anti-inflammatory, pneumonia, respiratory, malaria, TB, arthritis, leprosy, alcohol dependence, immune modulators, and anti-diarrhoea that are being tested.
But the Indian Council of Medical Research has approved a Lopinavir-Ritonavir fixed dose combination (FDC), that was originally prescribed for the treatment of HIV/AIDS, for Covid-19 patients. Clinical studies in drug repurposing and FDC, involve the testing of optimal dosage on limited number of patient cohorts. When time is of the essence, drug dosage and efficacy as well as side effects are clearly known for repurposed drugs. These drugs also offer the advantage of typically being off-patent (the older ones) and are already being manufactured by Indian generic pharmaceutical companies. The Task Force for Repurposing of Drugs ranked Favipiravir and Tocilizumab as the most promising to fight the disease.
The fresh arrival in the treatment armoury is Remdesivir, an RNA polymerase inhibitor; it stops the coronavirus from replicating. Gilead Sciences, USA, discovered Remdesivir to combat the 2014 Africa Ebola virus outbreak. It has now resurrected this molecule through an accelerated solidarity clinical trial.
Gilead owns the patent rights for Remdesivir, granted by the Indian Patent Office on February 18 this year. The manufacture and sale of Remedesivir will require terms to be negotiated between Indian drug firms and Gilead. Important observations made by the US National Institute of Allergy and Infectious Diseases (NIAID) and US Food and Drug Administration (US-FDA) are that Remdesivir can shorten recovery from 15 days to 11 and improve death rate from 11.6% to 8%. Remdesivir is administered intravenously, which implies that patients will need to be in a hospital setting.
Favipiravir is a purine nucleic acid analog and potent RNA dependent RNA polymerase inhibitor approved for use in influenza. Both “virs” act by a similar RNA virus cell disruption mechanism. A few Indian firms have been granted permission for clinical trials on Favipiravir, including the Council of Scientific and Industrial Research (CSIR).
Published results of a clinical trial of Favipiravir show that out of 80 patients, 35 who got the drug demonstrated significantly shorter viral clearance time compared to 45 in the control arm (those who didn’t) – with median recovery of four days compared to 11. The 7 days’ clinical recovery rate also increased from 55.86% to 71.43% in the drug arm.
Favipiravir is a bioavailable pill marketed as Avigan by Fujifilm in Japan. Patents were filed in India around the year 2000 and its manufacturing process for economical production is largely in place. The molecular complexity of Remdesivir (formula: C27 H35 N6 O8 P), together with chirality of the molecule or a single-handedness, mean that its synthesis difficulty and manufacturing process will be a bigger challenge and with a higher cost than Favipiravir (C5 H4 F N3 O2). Remdesivir is a new drug with its synthetic route and a scale-up unoptimized as of today.
Favipiravir could be an affordable COVID-19 drug, subject to favourable outcome in human clinical trials.
The writer is director, CSIR-National Chemical Laboratory, Pune, and a senior professor of chemistry, Hyderabad Central University. The views expressed are personal