A decade after it first failed, a Shire-developed Takeda antiviral appears successful in Phase III
Nearly 20 years after it first entered the clinic and over a decade after it first flunked a Phase III trial, a Takeda-owned drug to treat CMV infections has proven effective in a late-stage study.
Takeda didn’t break down all the numbers, but said that in a 352-person trial, maribavir outperformed physician’s choice in clearing infections in transplant patients who were resistant to current treatments. In a statement, Obi Umeh, Takeda’s maribavir program leader, said they would take the data to regulators in the US and Europe.
CMV, or cytomegalovirus, is a common virus that affects much of the population without causing symptoms, but it can be dangerous to people whose immune systems are compromised, such as recipients of bone marrow or organ transplants.
“Today, transplant patients who do not respond or experience adverse events related to existing therapies may be at higher risk for complications from the virus, including transplant failure and death,” Umeh said. “Maribavir has the potential to redefine management of post-transplant CMV infections by helping patients clear the virus with less treatment limiting toxicities.”
An approval would give Takeda one of the first big wins from the Shire buyout and mark the culmination of a wild, two-decade ride for a drug GlaxoSmithKline first synthesized two decades ago. In 2003, after some early work in the clinic, the then antiviral-focused Big Pharma licensed the drug to the rare disease and infectious disease-focused biotech ViroPharma.
ViroPharma advanced the drug, with positive results, through Phase II, but in 2009, it missed the primary endpoint on a Phase III study, failing to prevent CMV infections better than placebo in patients receiving bone marrow transplants. ViroPharma went back to the drawing board, eventually arguing that a higher dosage might lead to a better response.
In 2013, though, the drug left ViroPharma’s hands and passed to Shire, which bought out the entire biotech for $4.2 billion. The Irish drugmaker upped the dosage and ran the drug through a smattering of pharmacokinetic and efficacy studies, testing whether giving 4 to 12 times the amount of drug might improve performance.
In 2016, they showed efficacy in a Phase II study that 400mg, 800mg, and 1200mg helped clear infection. Based off those results, the FDA handed the company breakthrough designation. The most recent Phase III used 400 mg, or four times the dosage of the Phase III that failed in 2009.
The same year it received breakthrough designation, the compound served as one of the assets in Takeda’s decision to buy out Shire for $62 billion. GlobalData projected that it could earn around $200 million per year in sales by 2023.
Still, key questions remain for the drug. Takeda has yet to break down the safety data, which appeared to be a concern in a recent Phase II study. Last year, the company announced results from a trial comparing maribavir to the Roche antiviral Valcyte. Maribavir was better at clearing infection, but Valcyte appeared safer: Two thirds of the maribavir group saw treatment-related adverse events, compared to one fifth of Valcyte patients.