Alles über Lagevrio (Molnupiravir): das erste orale Virostatikum gegen COVID-19 | Neues COVID-19-Medikament

Artikel geprüft von Dr. Jan de Witt

On the 4th of November 2021, the Medicines and Healthcare products Regulatory Agency (MHRA) of the UK approved Lagevrio (molnupiravir) after reviewing its safety and effectiveness. Molnupiravir is the first oral antiviral for COVID-19 to be approved and the UK is the first country to approve it.

MHRA considers molnupiravir effective at reducing the risk of hospitalisation and death and authorised it for use in people who have mild to moderate COVID-19 and at least one risk factor for developing severe illness.

What makes molnupiravir different than other treatments is that it’s an oral tablet that could, depending on the type of approval it receives in each country, be taken outside of the hospital. The projected cost of around $700 per person for a 5-day course is cheaper than other treatments (such as remdesivir, an antiviral injection that costs $3,120 per treatment course), but not yet affordable as an over the counter medicine.

Molnupiravir ist für Patienten außerhalb des Vereinigten Königreichs im Rahmen eines "compassionate use" oder auf Basis eines benannten Patienten verfügbar. Erfahren Sie mehr, indem Sie zum Abschnitt "Zugang zu Lagevrio (Molnupiravir) außerhalb Großbritanniens" springen.

What is Lagevrio (molnupiravir)?

Molnupiravir ist ein oral verabreichtes antivirales Medikament, das die Replikation bestimmter RNA-Viren hemmt und zur Behandlung von COVID-19 eingesetzt wird.

Molnupiravir is not a new treatment developed specifically for the coronavirus SARS-CoV-2. Research began in 2003 and it was initially developed to treat influenza at Emory University’s non-profit company DRIVE (Drug Innovation Ventures at Emory) in Atlanta, USA. In 2015, DRIVE’s chief executive George Painter offered it to a collaborator, virologist Mark Denison at Vanderbilt University in Nashville, to test against coronaviruses and found it worked against coronaviruses like MERS and mouse hepatitis virus.

When the pandemic started in early 2020, DRIVE licensed molnupiravir to Ridgeback Biotherapeutics, a biotechnology company that had previously developed a monoclonal antibody for Ebola, in hopes to fight against the coronavirus SARS-CoV-2 that causes the COVID-19 disease. Ridgeback soon partenered with the pharmaceutical giant Merck to accelerate its development.

The Emory researchers named their drug molnupiravir, after Mjölnir—the hammer of Thor.

Wie wirkt Lagevrio (Molnupiravir)?

Mechanism of action

When SARS-CoV-2 enters a cell, the virus needs to duplicate its RNA genome to form new viruses. Molnupiravir gets incorporated into RNA strands and mutates in random ways, so the virus then duplicates with mutations and over time, it causes more mutations that eventually kill the virus.

"Das nennen wir letale Mutagenese. Das Virus mutiert sich im Grunde selbst zu Tode", sagt Richard Plemper, Virologe an der Georgia State University in Atlanta.

Because the mutations accumulate randomly, it’s difficult for viruses to evolve resistance to molnupiravir, which means the drug is effective against COVID-19 variants.

A full course treatment consists of four pills taken twice a day for a total of five days, starting no later than five days after the onset of symptoms.

Clinical trial

The latest trial, a Phase III trial conducted by Merck, was carried out globally in over 170 trial centers. The selected patients were required to have at least one risk factor associated with poor disease outcome (such as diabetes or heart disease) and received molnupiravir or placebo after they observed mild to moderate symptoms.

According to an interim analysis assessing results from 775 subjects, molnupiravir lowered hospitalisation or mortality risk by nearly 50% and was effective against all variants, including the Delta variant. From the group that was given molnupiravir, no deaths were observed, as opposed to 8 deaths in the placebo group.

A previous trial showed no benefit in treating patients already in the hospital with COVID-19.

Merck ist nicht das einzige Unternehmen, das Molnupiravir erforscht. Im Oktober wollten zwei indische Arzneimittelhersteller, Aurobindo Pharma Ltd. und MSN Laboratories, die unabhängig voneinander Molnupiravir-Generika bei Menschen mit mäßigen COVID-19-Symptomen an einer Mischung aus nicht hospitalisierten und hospitalisierten Personen testen, die Versuche in der Spätphase beenden, da sie keine signifikanten Verbesserungen sahen, aber die Versuche bei Menschen mit leichten Symptomen, die nicht hospitalisiert waren, fortsetzen. Merck-Sprecher erklären, dass die indischen Unternehmen den Begriff "mittelschwere Erkrankung" anders definieren als die US-amerikanischen und in ihre Untersuchungen auch Personen einbezogen haben, die nach US-amerikanischer Definition "schwer krank" waren.

Some experts however doubt the usefulness of the drug.

Dr. Peter English, ein pensionierter Facharzt für übertragbare Krankheiten und ehemaliger Vorsitzender des Ausschusses für öffentliche Gesundheitsfürsorge der British Medical Association, sagte: "Das Problem bei antiviralen Medikamenten wie Molnupiravir von Merck ist, dass sie eingesetzt werden müssten, bevor die Menschen (normalerweise) als krank genug gelten, um etwas anderes als eine symptomatische Selbstbehandlung zu benötigen. Solange ein antivirales Medikament nicht so billig und sicher gemacht werden kann, dass es von Menschen, die COVID-19 haben könnten, 'auf Bestellung' eingesetzt werden kann, ist es unwahrscheinlich, dass es von großem Nutzen ist".

Safety concerns

Some experts have raised safety concerns due to molnupiravir’s mechanism of action. Molnupiravir causes viral RNA to mutate and there are concerns that it could cause other cells to mutate as well, causing cancer or causing abnormalities in developing fetuses. One study in animal cell cultures found mutations in cells treated with molnupiravir.

In den klinischen Studien von Merck waren schwangere oder stillende Frauen von der Teilnahme ausgeschlossen, und Frauen im gebärfähigen Alter mussten für die Dauer der Studie Verhütungsmethoden anwenden oder abstinent sein (Männer wurden ebenfalls aufgefordert, zu verhüten oder abstinent zu sein). In den Teilnahmebedingungen schreibt Merck: "Die Behandlung mit EIDD-2801 ist bei schwangeren oder stillenden Frauen und bei den männlichen Partnern von schwangeren Frauen kontraindiziert."

Dr. Peter Hotez, an infectious disease specialist at the Baylor College of Medicine, notes there isn't any reason to think that molnupiravir would interfere with human genetics: "It's more of a theoretical concern, but it's something to keep in mind."

Die MHRA schreibt in ihren jüngsten Dokumenten zur Zulassung von Molnupiravir im Vereinigten Königreich, dass Molnupiravir nicht für die Anwendung bei Schwangeren empfohlen wird, und empfiehlt, dass Personen im gebärfähigen Alter "während der Dauer der Behandlung und vier Tage nach der letzten Dosis von Lagevrio (Molnupiravir) eine wirksame Empfängnisverhütung anwenden".

What is the approval status of Lagevrio (molnupiravir)?

Molnupiravir was approved in the UK in November 2021, a few weeks after the UK had purchased 480,000 courses of the drug from Merck. The UK will conduct a national study to gather more data about its effectiveness and will treat both vaccinated and unvaccinated patients.

Merck has filed for emergency approval for molnupiravir in the US and Canada, while the European Medicines Agency (EMA) has started reviewing the drug. The US has already purchased 1.7 million courses of the drug for approximately $1.2bn, while other wealthy countries, such as South Korea and Australia, have made purchase agreements or are currently in talks with Merck.

At the time of writing this article, 25 November 2021, the FDA was reviewing molnupiravir. At a White House COVID-19 briefing, Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, called the trial results "very encouraging," but said the drug needs close scrutiny by the FDA.

Accessing Lagevrio (molnupiravir) outside of the UK

Molnupiravir is currently approved and available for UK residents — and there are regulations that allow for medicines to be imported in countries where they are not currently approved.

Patienten mit lebensbedrohlichen oder schwächenden Krankheiten haben das Recht auf Zugang, Kauf und Import von Medikamenten mit Hilfe ihrer behandelnden Ärzte.

Patienten und ihre Ärzte können dies auf Basis der "compassionate use" oder "named patient import regulations" tun, einer gesetzlichen Ausnahme von der allgemeinen Regel, dass ein Medikament normalerweise erst nach der Marktzulassung/Zulassung (welche Formulierung wir auch immer verwenden) in dem Land, in dem der Patient lebt, zugänglich ist. Diese Ausnahme ermöglicht es Patienten, auf legale, ethische und sichere Weise Zugang zu Medikamenten zu erhalten, die in ihrem Land noch nicht zugelassen sind.

Mehr über die "named patient basis" erfahren Sie hier (EMA).

We are currently making efforts into sourcing molnupiravir so we can help you access Lagevrio (molnupiravir).

Upcoming medicines for COVID-19

Merck is trying to bridge that gap when it comes to molnupiravir. It recently granted royalty-free licenses to the Medicines Patent Pool, a U.N.-backed nonprofit, which will allow manufacturers to produce generic versions of the drug for more than a hundred low- and middle-income countries.

Merck is also researching whether molnupiravir could prevent infection after exposure to COVID-19. If it does, the drug could possibly be taken prophylactically when a person comes into contact with someone infected.

Paxlovid is another antiviral pill (produced by Pfizer) that shows effectiveness against COVID-19 and also sits with the FDA to be reviewed and potentially approved for use.

In November 2021, the EMA recommended authorising Ronapreve (casirivimab/imdevimab) and Regkirona (regdanvimab) for mild to moderate COVID-19 illness.

Other drugs under review by the EMA are:

• Paxlovid (PF-07321332; Ritonavir)
• Kineret (anakinra)s
• Olumiant (baricitinib)
• RoActemra (Tocilizumab)
• Xevudy (sotrovimab)
• Evusheld (tixagevimab / cilgavimab)