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Date of publication:2019/12/4 15:49:07
With thousands of people getting the flu every year, and many people becoming seriously ill, having safe and effective treatment alternatives is critical.

Baloxavir marboxil, marketed as Xofluza, is a first-in-class, one-dose oral agent first approved by the FDA in 2018 for the treatment of acute, uncomplicated influenza in individuals 12 years and older, who have been symptomatic for less than 24 hours. It is the first new antiviral with a novel mechanism of action to treat influenza in 20 years.
Baloxavir-Marboxil
Baloxavir marboxil
 
Baloxavir vs Oseltamivir

Baloxavir marboxil differs from oseltamivir (marketed as Tamiflu, also available generic) in its mechanism of action.

Influenza viral infection occurs when hemagglutinin on the envelope surface binds to receptors on the cell surface of the human airway. Virus ribonucleoprotein (RNP) complex is released in the intracellular space (shelling), and migrates into the nucleus. Messenger RNA (mRNA) synthesis by viral RNA transcription and viral genome RNA replication are separately promoted. As an RNA polymerase inhibitor, baloxavir marboxil, inhibits mRNA synthesis. Viral polymerase consists of PA, PB1, and PB2. Baloxavir marboxil hinders mRNA synthesis by inhibiting the cap-dependent endonuclease of PA, suppressing virus proliferation.

On the other hand, Oseltamivir inhibits the action of the viral enzyme neuraminidase (which lets viruses bud and spread from the infected cell).

 
Baloxavir-Marboxil-Mechanism-of -Action
Baloxavir Marboxil Mechanism of Action, Image Source: nejm.org
Last year, Hayden and his colleagues published a study in the New England Journal of Medicine that compared baloxavir with placebo and oseltamivir. The study found the following results:

Baloxavir marboxil met its primary and secondary endpoints compared to placebo:
  • ​ Significantly reduced the duration of flu symptoms by more than one day (median time 53.7 hours versus 80.2 hours; p<0.0001);
  • ​ Significantly reduced the duration of fever by nearly a day (median time 24.5 hours versus 42.0 hours; p<0.0001);
  • ​ Significantly reduced the length of time viruses continued to be released from the body (median time of viral shedding; 24.0 hours versus 96.0 hours; p<0.0001);
  • ​ Significantly reduced the levels of virus in the nose and throat from 24 hours through 120 hours.

Similar efficacy results were seen between baloxavir marboxil and oseltamivir in relation to the duration of symptoms and fever reduction, but significant differences were observed in time to cessation of viral shedding favoring baloxavir marboxil:
  • ● No significant reduction in duration of symptoms (median time 53.5 hours versus 53.8 hours; p=0.7560);
  • ​ No significant reduction in time to resolution of fever (median time 24.4 hours versus 24.0 hours; p=0.9225);
  • ​ Significantly reduced the length of time the virus continued to be released from the body (viral shedding; 24.0 hours versus 72.0 hours; p<0.0001);
  • ​ Significantly reduced the levels of virus in the nose and throat at 24 hours and 72 hours.

Baloxavir marboxil was well-tolerated and had a numerically lower overall incidence of adverse events (20.7 percent) reported compared with placebo (24.6 percent) oroseltamivir (24.8 percent). The most common adverse events reported were diarrhea (3.0 percent), bronchitis (2.6 percent), nausea (1.3 percent) and sinusitis (1.1 percent), and all of these adverse events occurred at a lower frequency than placebo.

In addition, according to the Japan Times, NIID said that a mutant influenza virus resistant to baloxavir was found in patients in December 2018. This is the first influenza virus mutation discovered by a national research institution since the drug was put into practical use.

In December 2018, two of four elementary school students in Yokohama were found to be resistant to the Xofluza virus during a general screening after they had earlier developed flu symptoms. The mutant virus is 76-120 times more resistant to the drug than the unmutated virus detected by the other two children.

In clinical trials of the drug, drug-resistant viruses were detected in 23.4% of subjects younger than 12 years of age.

Anyway, there will be challenges. It will take time to work through the difficulties.

Huateng Pharma, a professional manufacturer of pharmaceutical API and intermediates, provides Baloxavir Marboxil intermediates with capacities varying from gram to kilograms. 

Baloxavir Marboxil intermediates: CAS No. 1985606-14-1CAS NO. 1985607-83-7, ​CAS NO. 1985607-70-2CAS No. 2136287-66-4CAS NO. 2136287-68-6


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