Leading experts have now declared at a round table discussion of the general medicine initiative AM Plus in Vienna: They are not “game changers”. The Covid-19 vaccination remains the be-all and end-all of the fight against the pandemic.
“The most important thing is always the vaccination. After that there is nothing for a long time, then nothing – and only then medication,” said the Viennese infectiologist Florian Thalhammer (MedUni Vienna / AKH). Christa Wirthumer-Hoche, head of the AGES medical market supervision, said in the same sense: “None of these drugs are game changers.”
Nevertheless, the new drugs represent a step forward: They are molnupiravir (Merck, Sharp and Dohme), which is already approved in Great Britain and will also be available in Austria to a very limited extent in a special program (compassionate use) in the near future the SARS-CoV-2 protease inhibitor combination therapy nirmatrelvir / ritonavir (Pfizer), which has just been granted emergency approval in the USA. Both therapies are under review by the European Medicines Agency (EMA). Unlike monoclonal antibodies, which are primarily used in clinics, they are intended for use outside of hospitals.
The mechanisms of action: Molnupiravir works by using SARS-CoV-2-infected cells that produce new particles to subjugate false RNA building blocks and thus stop virus replication. Nirmatrelvir inhibits an important SARS-CoV-2 protease enzyme. This suppresses the maturation and infectivity of the Covid-19 pathogen. The additional substance ritonavir, as a second protease inhibitor, is intended to delay the breakdown of nirmatrelvir.
The advantage: Both drugs are synthetically producible active ingredients. They will be available for oral consumption. This takes place over five days.
No therapy for pregnant women and children
But there are numerous restrictions: The phase III study on the efficacy and tolerability of molnupiravir published a few days ago in the New England Journal of Medicine showed a 30 percent reduction in the frequency of hospital admissions and deaths in Covid 19 patients with initially mild to moderate disease course and at least one risk factor (age over 60, obesity, chronic kidney disease, diabetes, cancer, etc.). It has undoubtedly shown a significant effect, but molnupiravir is not a “miracle drug”. A positive aspect, as Thalhammer demonstrated: After three days, only five percent of those treated had excreted the virus, after five days for none of the test subjects. According to the data available to date, nirmatrelvir / ritonavir has the potential to reduce the risk by as much as 89 percent (severe course, deaths).
Pregnant women and children are out of the question for these therapies. Serious drug interactions can also occur.
Probably the biggest limitation: The production quantities for both drugs will initially be far too low to make them freely prescribable and available. This means that a system will be used in Austria that was already used for the formerly just as scarce Remdesvir or other first Covid-19 therapies: In every federal state, a hospital pharmacy acts as the central Covid-19 pharmacy (also Single Point of Communication; SPOC). The need for the drugs is recorded for each federal state; this also depends, for example, on the regional Covid-19 incidence rates. The SPOC pharmacy orders the necessary quantities. Then the distribution takes place from there. The data is sent back to the medical market regulator, where the activity is monitored. This is to ensure that the application is as fair and competent as possible.
This is what the schedule for molnupiravir looks like in Austria: It is expected that the first around 12,000 packs will be available in the system shown (compassionate use) from around December 28th. The individual federal states will probably have to organize the processing according to their regional circumstances – the city of Vienna is structured differently than “federal states”.
Vaccinations are a priority
However, since both molnupiravir and nirmatrelvier / ritonavir are being assessed by the EMA, approvals in the EU can be expected in the near future, based on the models in Great Britain (molnupiravir) and the USA (combination therapy). Only then could the Covid-19 drugs be more freely prescribable, for example by general practitioners. However, there remains the limitation of the quantitative availability and the strict requirement in the selection of suitable patients. The corresponding rules for processing still have to be drawn up.
The first requirement: an acute SARS-CoV infection documented in a laboratory. “The earlier the drugs are then taken, the better,” stressed Thalhammer. Similar to influenza drugs with a specific effect, the best assumption is that they are taken within two to three days of the onset of symptoms.
Erwin Rebhandl, President of AM Plus, has been working as a family doctor in Upper Austria for decades and is now co-operator of a primary care center, summarized the conditions as follows: “We need a positive PCR test. Then we need a precise definition of who is at risk (Risk of a serious illness; note). We have to take the time factor into account. The financing must be regulated – and we need the medication in the ordination software. ” The latter would only allow a simple check for interactions with an otherwise existing medication quickly.
In an international comparison, Austria is probably quite early on with the two drug therapies. For example, until a week ago, molnupiravir was not used anywhere in the world outside of clinical studies, explained Christa Wirthumer-Hoche. You should use the time now to optimally prepare for these challenges. Of course, using the time for additional first vaccinations and the third vaccination has an overriding priority in comparison.
Source: Nachrichten
