Post by icemandios on Jul 25, 2022 19:21:01 GMT
July 25, 2022 12:37 PM EDTUpdated 02:52 PM Coronavirus
Pfizer considers antiviral options as Paxlovid use skyrockets amid worries of resistance
Zachary Brennan
Senior Editor
When Pfizer’s Covid-19 antiviral Paxlovid first hit the shelves last December, it was widely seen as the best option to keep those at high risk of hospitalization out of the hospital.
But that early caution with regard to who received the pill has generally been thrown into the wind as almost a million Americans per month (or about 1 in every 4 officially reported Covid-19 case) now uses the antiviral, according to the latest US government data. The spike in usage comes as pharmacists are now allowed to offer Paxlovid in the US, and as Pfizer begins to weigh its options with regard to combo treatments and a second-generation antiviral.
“We have to make sure we are using Paxlovid in those who will benefit and avoiding use in those who don’t need it,” Walid Gellad, director of the Center for Pharmaceutical Policy and Prescribing at the University of Pittsburgh, told Endpoints News. “I don’t think we are striking that right balance yet, especially as we face looming uncertainty on what the fall brings us. In addition to the number of prescriptions we also need transparency in who those prescriptions are going to.”
Higher risk for severe Covid is defined by CDC as having an underlying medical condition or risk factor, which can include conditions like asthma or obesity, or be based on age or status as a current or former smoker. But more than 35 different drugs are contraindicated with Paxlovid, according to the FDA fact sheet,
Part of the reason that worries are increasing related to the overuse of Paxlovid is the threat of resistance.
Chemist and Science writer Derek Lowe recently penned a post on how resistance is a question of when, not if, for Paxlovid, explaining:
I’d say that: (1) mutations in the coronavirus are definitely taking place in response to Paxlovid therapy, (2) that there are a number of regions in the protein sequence that could (in theory) lead to viral sequences that are still reproductively fit but are much less affected by Paxlovid, and (3) that a number of potential mutation sites identified by these in vitro studies also have appeared in mutations isolated from wild-type coronavirus in humans, showing that they are feasible under real-world conditions.
Meanwhile, HHS data show that 40% of all Paxlovid used so far has been used in June and this month.
“The likelihood of resistance is high,” Eric Topol, director of the Scripps Research Translational Institute, told Endpoints. “Many Mpro [main protease] function mutations, occurring naturally, have already been identified.”
A Pfizer spokesperson told Endpoints the company is working to minimize “the probability of resistant mutations appearing” and working on “proactively evaluating a multi-pronged strategy to be at the ready should resistance develop. This includes thinking ahead to second-generation antivirals and potential for combination therapy, among others.”
But the spokesperson noted that nirmatrelvir, the active protease inhibitor component of Paxlovid, “binds tightly in the binding pocket of the main protease (Mpro), making it more challenging for the protease to mutate — an approach that raises the barrier for resistance to develop. We have not seen any significant treatment-emergent mutations in the Mpro to date, and current variants of concern can be resistant to treatments that work by binding to the spike protein found on the surface of the SARS-CoV-2 virus.”
Outside of the US, however, uptake of Paxlovid has been considerably slower. The Financial Times reported on Monday that, “By the end of 2022 there could be a surplus of up to 70mn courses of Paxlovid on the global market following an increase in production by Pfizer” as countries like Germany and Italy combined haven’t even hit 100,000 Paxlovid courses administered yet.
Pfizer considers antiviral options as Paxlovid use skyrockets amid worries of resistance
Zachary Brennan
Senior Editor
When Pfizer’s Covid-19 antiviral Paxlovid first hit the shelves last December, it was widely seen as the best option to keep those at high risk of hospitalization out of the hospital.
But that early caution with regard to who received the pill has generally been thrown into the wind as almost a million Americans per month (or about 1 in every 4 officially reported Covid-19 case) now uses the antiviral, according to the latest US government data. The spike in usage comes as pharmacists are now allowed to offer Paxlovid in the US, and as Pfizer begins to weigh its options with regard to combo treatments and a second-generation antiviral.
“We have to make sure we are using Paxlovid in those who will benefit and avoiding use in those who don’t need it,” Walid Gellad, director of the Center for Pharmaceutical Policy and Prescribing at the University of Pittsburgh, told Endpoints News. “I don’t think we are striking that right balance yet, especially as we face looming uncertainty on what the fall brings us. In addition to the number of prescriptions we also need transparency in who those prescriptions are going to.”
Higher risk for severe Covid is defined by CDC as having an underlying medical condition or risk factor, which can include conditions like asthma or obesity, or be based on age or status as a current or former smoker. But more than 35 different drugs are contraindicated with Paxlovid, according to the FDA fact sheet,
Part of the reason that worries are increasing related to the overuse of Paxlovid is the threat of resistance.
Chemist and Science writer Derek Lowe recently penned a post on how resistance is a question of when, not if, for Paxlovid, explaining:
I’d say that: (1) mutations in the coronavirus are definitely taking place in response to Paxlovid therapy, (2) that there are a number of regions in the protein sequence that could (in theory) lead to viral sequences that are still reproductively fit but are much less affected by Paxlovid, and (3) that a number of potential mutation sites identified by these in vitro studies also have appeared in mutations isolated from wild-type coronavirus in humans, showing that they are feasible under real-world conditions.
Meanwhile, HHS data show that 40% of all Paxlovid used so far has been used in June and this month.
“The likelihood of resistance is high,” Eric Topol, director of the Scripps Research Translational Institute, told Endpoints. “Many Mpro [main protease] function mutations, occurring naturally, have already been identified.”
A Pfizer spokesperson told Endpoints the company is working to minimize “the probability of resistant mutations appearing” and working on “proactively evaluating a multi-pronged strategy to be at the ready should resistance develop. This includes thinking ahead to second-generation antivirals and potential for combination therapy, among others.”
But the spokesperson noted that nirmatrelvir, the active protease inhibitor component of Paxlovid, “binds tightly in the binding pocket of the main protease (Mpro), making it more challenging for the protease to mutate — an approach that raises the barrier for resistance to develop. We have not seen any significant treatment-emergent mutations in the Mpro to date, and current variants of concern can be resistant to treatments that work by binding to the spike protein found on the surface of the SARS-CoV-2 virus.”
Outside of the US, however, uptake of Paxlovid has been considerably slower. The Financial Times reported on Monday that, “By the end of 2022 there could be a surplus of up to 70mn courses of Paxlovid on the global market following an increase in production by Pfizer” as countries like Germany and Italy combined haven’t even hit 100,000 Paxlovid courses administered yet.