In the foreseeable future, the first drugs in tablet form against Covid-19 will also be available in Austria. However, the availability is extremely limited at the beginning, and the application is continuously linked to strict requirements. During a conversation with the general medicine initiative AM Plus in Vienna, leading experts stated that this was not a “game changer”. 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, nothing comes for a long time, then nothing – and only then medication, ”said the Viennese infectiologist Florian Thalhammer from MedUni Vienna. Christa Wirthumer-Hoche, Head of the Medical Market Supervision of the Agency for Health and Food Safety (AGES), said: “None of these drugs are ‘game changers’.”
Should prevent a severe course
Nonetheless, the new drugs represent a step forward: they are molnupiravir, which has already been 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 product comes from the manufacturers Merck, Sharp and Dohme and received emergency approval for high-risk patients aged 18 and over in the USA on Thursday. The drug, also known in Europe under the name Lagevrio, is intended for the treatment of Covid-19 diseases with mild to moderate symptoms and is intended to prevent the disease from developing into a severe course.
The second candidate drug is Pfizer’s SARS-CoV-2 protease inhibitor combination therapy, nirmatrelvir / ritonavir, currently in the US for emergency approval. Both therapies are currently being assessed by the European Medicines Agency (EMA). Unlike monoclonal antibodies, which are primarily used in clinics, they are intended for use outside of hospitals.
Synthetically produced
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.
Effective, but “not a miracle cure”
But there are numerous restrictions: The phase III study published a few days ago in the “New England Journal of Medicine” on the efficacy and tolerability of molnupiravir showed a thirty 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.). There was no doubt a significant effect, but molnupiravir is not a “miracle cure”.
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.
Monitored delivery system
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 previously scarce remdesivir or other first Covid-19 therapies: In every federal state, a hospital pharmacy acts as the central Covid-19 pharmacy.
The need for the drugs is recorded for each federal state; this also depends, for example, on the regional Covid-19 incidence rates. The hospital 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.
It is expected that the first 12,000 packs of molnupiravir will be available in the compassionate use system 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 the “federal states”.
Waiting for approval
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 sooner the drugs are taken, the better,” said 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.
Quite a few hurdles
Erwin Rebhandl, President of AM Plus, who has worked as a family doctor in Upper Austria for decades and is now a 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 course of the disease, note). We have to take the time factor into account. The financing has to 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 had not been used anywhere outside of clinical studies, explained Wirthumer-Hoche. You should use the time now to optimally prepare for these challenges. The priority now is to use the time for additional first vaccinations and the third vaccination.