Author: Jean-Claude Muller, 穆卓Executive Editor at BtoBioInnovation firstname.lastname@example.org
SPECIAL REPORT #20.27
COVID Treatments (part 3)
Every single biopharmaceutical company is very cautious to assess the benefit-risk ratio of a drug it is going to develop, launch and commercialise across several countries and regions. The benefit-risk ratio is not just a single scale with a magic number to be obtained. This ratio needs to be assessed on the one hand by the clinical benefit provided by the drug, benefit which is directly linked to the impact a drug makes for a given disease. If there is no current treatment for a disease the accepted clinical outcome can be considerably lower than for a disease where standard therapy is already available. On the other hand, the ratio takes into account the number and the severity of the adverse effects induced by a drug, or a drug within a given combination. Low severity with a high number of subjects is unacceptable, high and uncontrollable severity within a low number of subjects is not more acceptable.
It is important at this stage to pinpoint to the fact that in most pivotal clinical trials, the benefit-risk ratio is continuously assessed by an independent drug safety monitoring board (DSMB) which has access to unblinded data and which advises the biopharmaceutical companies at what to do next. In addition, regulatory bodies are the ones who approve the market authorisation of a new drug based on their own benefit-risk assessment, authorisation which is regularly reassessed in view of the available real world safety data.
In the current context of suspicion that the investigational COVID-19 drugs and vaccines may not be assessed with the same rigor than other drugs, in part because of political pressure, it comes as no surprise that biopharmaceutical companies are not practicing the usual braggadocio of which drug is leading the pack and are particularly cautious on unexpected adverse effects. Patients and some experts are understandably worried about how early Emergency Use Authorisation (EUA) requested by most biopharmaceutical companies for their investigational COVID-19 treatments, will be affecting ongoing development and safety concerns.
This explains why within a few days AstraZeneca, Johnson & Johnson and Eli Lilly have put part or all of their ongoing clinical study with COVID-19 drugs or vaccines on hold.
In spite of its approved European Medicines Agency (EMA) rolling review for AstraZeneca and the University of Oxford’s AZD1222/ChAdOx1, their COVID-19 investigational vaccine, the US study has remained on hold since one month. In a UK study one patient developed transverse myelitis, an inflammation of the spinal cord.
On Tuesday Johnson & Johnson has put Ad26.COV2.S, its COVID-19 vaccine, on hold because of an unexplained illness in a study patients. “Right now we are waiting for the DSMB to do their analysis…. We still don’t know whether it’s in the placebo arm or the vaccination arm” J&J CFO, Joseph Wolk said on CNBC. Ad26.COV2.S uses the same adenovirus technology than Ervebo, the J&J’s approved Ebola vaccine. Both J&J and AstraZeneca are developing adenovirus-based vaccines whereas Pfizer and Moderna, the two other well advanced COVID-19 vaccines candidates, are mRNA vaccines.
Also on Tuesday, Eli Lilly called a halt on LY-CoV555, its phase 3 antibody monotherapy trial, after the DSMB identified an undisclosed safety concern. The ACTIV-3 trial is testing LY-CoV555 in combination with Gilead’s remsedivir, in ambulatory hospitalised patients. The company did not further comment at this stage.
Last week, at a coronavirus vaccine symposium, Operation Warp Speed head Moncef Slaoui said efficacy data on vaccines will be available over the next months with Pfizer and Moderna’s first wave in November and December. Interim results from Johnson & Johnson, expected in late December, may significantly be delayed if the hold remains for several weeks.
Paris October 14,2020.
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