Submit 28 days trial results of Hepatitis C drug for Covid-19: CDSCO panel to Zydus Cadila
New Delhi: In response to the drug major Zydus Cadila's proposal for marketing authorisation of the Hepatitis C drug, Pegylated Interferon Alpha-2b (PegIFN), for treating Covid-19 patients, the Subject Expert Committee (SEC), functional under Central Drug Standard Organization (CDSCO), has recently suggested that the firm should present complete 28 days clinical trial results before the committee, showing detailed results of primary and secondary outcomes.
The recommendation came after the committee noted that the data presented by the firm is interim clinical trial results for 15 days. Further, the committee noted that the data pertaining to the primary and secondary endpoints has not been presented adequately.
Pegylated interferon alfa-2b (PEG IFN-α2b) is a covalent conjugate of recombinant α2b interferon with monomethoxy polyethylene glycol. It binds to and stimulates human type 1 interferon receptors, allowing them to dimerize, resulting in JAK/STAT pathway activation. Activation of the JAK/STAT pathway boosts the expression of various genes involved in the innate antiviral response across multiple tissues. There are published results reporting the role of interferons in treating SARS-CoV and middle east respiratory syndrome coronavirus (MERS-CoV).
Moreover, a phase II, randomized, controlled, open-label study of pegylated interferon alfa-2b in moderate COVID-19 showed a significant improvement in clinical status on day 15, which is likely due to faster viral reduction compared to Standard of Care (SOC) with the PEG IFN-α2b treated moderate COVID-19 subjects showing a difference as early as day seven and becoming significant by day 14.
The Medical Dialogues team had earlier reported that Zydus Cadila had announced that its Phase III clinical trials with Pegylated Interferon Alpha 2b, PegiHep showed promising results in treating COVID-19. Further, the company declared that the interim results indicated that PegIFN, when administered early on, could help patients recover faster and avoid many of the complications seen in the advanced stages of the disease.
PegIFN in COVID19 has several add-on advantages compared to other anti-viral agents. The treatment regimen would be less cumbersome and more affordable for patients as Pegylated Interferon Alpha 2b, is a single dose regimen. It would also ensure better compliance.
Patients on Pegylated Interferon Alpha 2b during the trial also showed less need for supplemental oxygen, clearly indicating that it was able to control respiratory distress and failure, which has been one of the major challenges in treating COVID-19.
The Phase III trials demonstrated that a higher proportion of patients in the PegIFN arm showed a two-point statistically significant clinical improvement on day 8 as compared to the SOC arm (80.36% vs 68.18%). Additionally, a higher proportion of patients in the PegIFN arm were RT PCR negative by day 7 as compared to the SOC arm. Clinically the hours of supplemental oxygen required was significantly lesser in the PegIFN arm and as well as the time to resolution of signs and symptoms as compared to the SOC arm (5 days vs 6 days). Both the arms received standard of care, that included steroids in some patients.
A higher proportion of patients in the PegIFN arm were RT PCR negative by day 7 (95.77% vs 73.24%) as well as a two-point improvement on day 8 compared to the SOC arm with steroids (85.92% vs 67.57%). Both the arms received standard of care, that included steroids in some patients.
The findings are in line with the recently reported importance of early IFN treatment given in combination with steroids in the treatment of COVID-19 (Lu et al, Signal Transduction and Targeted Therapy (2021) 6:107)- a Nature publication. With these positive results, the Company applied for approval for additional indication with the DCGI for the use of PegIFN in the treatment of COVID 19.
Responding to the firm's proposal for Marketing authorisation based on the interim results of Phase III Clinical trial in COVID-19 patients, after detailed deliberation, the committee recommended that the firm should present complete 28-day clinical trial results before the committee, showing detailed results of primary and secondary outcomes.