Roche's investigative drug could become the first single-dose oral antiviral approved for the US market in December.
New results from the phase 3 CAPSTONE-2 trial show that Roche’s baloxavir marboxil could significantly reduce the time to improvement of influenza symptoms versus placebo—by more than a day, in patients at high risk of serious flu complications.
The trial data, announced at the 2018 IDWeek Annual Meeting in San Francisco, CA, on Thursday, also showed the single-dose investigational oral drug was well-tolerated in patients with no new safety signals identified. It adds to a portfolio which Roche officials believe indicate baloxavir marboxil as a first-in-class antiviral flu therapy.
CAPSTONE-2, a phase 3, multi-center, randomized, double-blind study comparing the efficacy and safety of the single-dose drug versus placebo and oseltamivir in people aged 12 years or older with high risk for flu complications, enrolled 2184 participants. People at high risk for serious flu complications, as defined by the US Centers for Disease Control and Prevention (CDC), includes adults aged 65 years or older, or those who have conditions such as asthma, chronic lung disease, morbid obesity, or heart disease.
In the patient population, 1163 (53%) were confirmed to have influenza virus infection with reverse transcription polymerase chain reaction (RT-PCR). Among them, 47.9% were diagnosed with A/H3N2 subtype, 41.6% with B, and 6.9% with A/H1N1. Common risk factors in the high-risk patients included asthma and chronic lung disease (39.2%), endocrine disorders (32.8%), age 65 years or older (27.4%), metabolic disorders (13.5%), heart disease (12.7%)
(influenza virus subtype: 47.9% for A/H3N2, 6.9% for A/H1N1, 41.6% for B). The most common risk factors were asthma or chronic lung disease (39.2%), age >= 65 years (27.4%), endocrine disorders (32.8%), metabolic disorders (13.5%), heart disease (12.7%), and morbid obesity (10.8%).
Patients were randomly assigned to single, oral baloxavir marboxil dose of 40 mg or 80 mg (based on body weight), placebo, or twice-daily 75 mg oseltamaivir for 5 days. Investigators sought a primary objective of measured time to improvement of influenza symptoms in single dose baloxavir marboxil versus placebo. Key secondary endpoints included compared outcomes in therapy versus placebo or oseltamivir including time to resolution of fever and cessation of viral shedding, infectious virus detection in nose and throat swabs, antibiotics prescriptions, and flu-related complications.
Investigators reported that patients treated with baloxavir marboxil reported a median time of 73.2 hours to improvement over flu symptoms, versus 102.3 hours in patients treated with placebo (P < .0001). Its efficacy versus was similar in patients diagnosed with either type A/H3N2 (75.3 vs 100.4; P < .05) and type B (74.6 vs 100.6; P < .05).
Patients on the investigative therapy still had numerically—though not statistically significant—shorter median time to improvement than patients treated with oseltamivir (81.0 hours; P = .8347). For patients with type B—known for being limited in antiviral efficacy response—baloxavir marboxil was significantly more efficacious than oseltamivir in reduction of time to improvement of symptoms (74.6 vs 101.6; P < .05).
In the secondary endpoints, baloxavir marboxil also significantly reduced time to viral shedding (48.0 hours) versus placebo and oseltamivir (96.0 hours; P <.0001), and reduced the use of antibiotics and incidence of flu-related complications (3.4% and 2.8%, respectively) versus placebo (7.5% and 10.4%, respectively; P = .01 and P < .05). In assessing for safety, patients on the investigative therapy had a lower incidence of reported adverse events (25.1%) than those on placebo (29.7%) or oseltamivir (28.0%).
Sandra Horning, MD, chief medical officer and head of Global Product Development for Roche, said this is the first phase 3 trial to demonstrate significant, clinically meaningful benefit in high-risk flu complication patients. It has significant meaning for a population without any currently approved therapies.
“This study adds to the growing body of evidence supporting baloxavir marboxil as a potential first-in-class antiviral flu treatment, and we plan to discuss these data with health authorities around the world,” Horning said in a statement.
Baloxavir marboxil, the first in a new class of antiviral drugs designed to inhibit cap-dependent endonuclease protein within the influenza virus, has already been approved and marketed in Japan as Xofluza for the treatment of influenza types A and B in pediatric and adult patients.
The US Food and Drug Administraion had previously accepted the company’s New Drug Application and granted the therapy Priority Review as a single-dose, oral treamtnet for acute, uncomplicated influenza in patients 12 years and older—based on the results of CAPSTONE-2 and a previous phase 2 trial.
Whether baloxavir marboxil becomes the first single-dose oral antiviral approved for the US market will be decided by its PDUFA date of December 24 of this year.
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