The combination of the active substances nirmatrelvir and ritonavir has been approved since January 2022 for the treatment of COVID-19 in adults who do not require supplemental oxygen and who are at increased risk of the disease becoming severe. The German Institute for Quality and Efficiency in Health Care (IQWiG) now examined in an early benefit assessment whether the drug known as Paxlovid offers an added benefit in comparison with the appropriate comparator therapy (ACT) “treatment of physician’s choice” for these high-risk patients. According to the findings, taking the drug combination reduces the risk of progressing to severe COVID-19, receiving intensive care or even dying from COVID-19.
However, as the relevant study was conducted exclusively in unvaccinated patients and it is unclear to what extent the effects are transferable to vaccinated patients, IQWiG overall determined only a “hint” of a major added benefit of nirmatrelvir/ritonavir in comparison with the ACT.
“This study showed a promising effect of Paxlovid in unvaccinated at-risk patients who have only been symptomatic for a few days and are not yet severely ill,” says IQWiG Director Jürgen Windeler. “However, the numerous interactions with other drugs that are frequently prescribed, especially in this target group, may limit its applicability.”
Fewer severe courses with Paxlovid®
In its dossiers, the drug manufacturer presented data from the EPIC-HR study. This study included non-hospitalized, symptomatic patients in the early phase of COVID-19 who had an increased risk for progression to severe disease. The following risk factors were taken into account: being overweight, being over 60 years old, taking immunosuppressive drugs, cigarette consumption, or having specific pre-existing conditions such as cardiovascular disease, diabetes mellitus (type 1 or 2) or chronic lung disease. All patients included in the study were unvaccinated, however. IQWiG also points out that patients with complex risk factors were under-represented in the EPIC-HR study.
The subpopulation of the EPIC-HR study relevant to IQWiG’s early benefit assessment included a total of 1908 patients, of whom 944 were treated with nirmatrelvir/ritonavir and 964 with placebo.
In the intervention arm of the study, no one had died 28 days after symptom onset, but 15 deaths (1.6 percent of patients) had occurred in the comparator arm. The number of severe courses of COVID-19 was also notably lower under treatment with nirmatrelvir/ritonavir: There were 10 (1.1 percent) severe COVID-19 courses in the intervention arm compared with 60 (6.2 percent) in the comparator arm. No patients in the nirmatrelvir/ritonavir group required intensive care, while 9 patients (0.9 percent) in the placebo group did. Symptom relief occurred after an average of 16 days of treatment with nirmatrelvir/ritonavir, and after 20 days without this therapy.
Overall, IQWiG sees a hint of a major added benefit of nirmatrelvir/ritonavir compared with the ACT “treatment of physician’s choice” for adults with COVID-19 who do not require supplemental oxygen and who are at increased risk of the disease becoming severe.
G‑BA decides on the extent of added benefit
The dossier assessment is part of the early benefit assessment according to the Act on the Reform of the Market for Medicinal Products (AMNOG) supervised by the Federal Joint Committee (G-BA). After publication of the dossier assessment, the G-BA conducts a commenting procedure and makes a final decision on the extent of the added benefit.
More English-language information will be available soon (extract of the dossier assessment). If you would like to be informed when these documents are available, please send an e-mail to firstname.lastname@example.org.