A fast-acting drug that shortens influenza infections with a single dose has earned a priority review from the US Food and Drug Administration and—if approved—has the chance of hitting the market in 2019 amid the upcoming flu season. That’s all according to Genentech, the Roche-based company that is developing the drug, baloxavir marboxil, for the US market.
Baloxavir marboxil is garnering attention in part because of its timing. It’s arriving in the wake of a “high-severity” flu season for the US and a sub-optimal seasonal vaccine. The Centers for Disease Control and Prevention logged record-level rates of hospitalizations for the 2017-2018 flu season and a high tally of 171 pediatric deaths. But the new flu drug also has notable advantages over the small number of other medications currently on the market for the seasonal affliction.
First, baloxavir marboxil is effective as a single dose. Genetech’s other flu drug, Tamiflu (oseltamivir phosphate), needs to be taken twice a day for five days within 48 hours of the onset of flu symptoms. Baloxavir marboxil, on the other hand, is taken in one bout in the same timeframe.
In a randomized, placebo-controlled phase III clinical trial of 1,494 people, baloxavir marboxil knocked back how long flu symptoms lasted by about a day, getting the illness to last for only about 54 hours instead of the 80 or so it lasted with a placebo. That about matches what Tamiflu can muster. But in the same trial, baloxavir marboxil proved better than Tamiflu at reining in viral shedding from infected peoples’ noses and throats. Snotty patients only spewed infectious particles for 24 hours after baloxavir marboxil, while Tamiflu-treated patients remained viral fountains for 72 hours after starting meds. The shorter shedding time could mean less infection all around.
A new weapon
Baloxavir marboxil uses a unique method to take out influenza virus. It targets an enzyme called cap-dependent endonuclease protein, which is critical for the virus’ ability to churn out copies of its genetic material to make the infectious clone army it assembles within infected human cells. Tamiflu and a few other flu drugs are neuraminidase inhibitors. They work by targeting the viral enzyme neuraminidase, which the germ uses to bust out of human cells—unleashing its clone armies to storm more cells.
Because baloxavir marboxil uses a novel flu-crippling method, it could be useful for treating flu strains that have become resistant to neuraminidase inhibitors, such as certain strains of avian H5N1 and H7N9. The FDA is eager to add such new drugs to its coffers. As FiercePharma pointed out, FDA Commissioner Scott Gottlieb stated in a congressional hearing on flu preparedness in March that “I think the bottom-line message is that we are very interested in having a spectrum of antiviral drugs that act differently, at different points in the virus. In case the virus itself becomes resistant to one approach at targeting the virus, we have backups and we have alternative approaches.”
Genentech said that it expects the FDA will make a decision on baloxavir marboxil’s approval by December 24, 2018. In an interview with Stat, Mark Eisner, a vice president of product development for Genentech, said that the company is “working very hard to make it available as soon as possible after approval. And we will work with FDA to do everything we can to expedite” the process.
The drug is already available in Japan by Roche-partner Shionogi & Co., Ltd., which discovered the drug and still holds rights to it in Japan and Taiwan. Shionogi got approval in Japan this past February and markets baloxavir marboxil under the name Xofluza. That version sells for the equivalent of $43.50, Stat points out. Roche, meanwhile holds worldwide rights elsewhere and hasn’t announced a US brand name or potential list price for the drug to be sold by Genentech.