Japan's PMDA reviews hep B risk link to hep C therapies

Japan's Pharmaceuticals and Medical Devices Agency (PMDA) is reviewing approved hepatitis C drugs in the country for links to a possible reactivation of the hepatitis B virus, which could result in label changes.

In a notice last week, PMDA said that the review covers Gilead Sciences' ($GILD) Sovaldi (sofosbuvir) and Harvoni (ledipasvir and sofosbuvir) as well as AbbVie's ($ABBV) Viekirax (ombitasvir and paritaprevir and ritonavir), Bristol-Myers Squibb's ($BMY) Daklinza (daclatasvir) and Sunvepra (asunaprevir), Mitsubishi Tanabe's Telavic (telaprevir), Janssen Pharmaceutical K.K.'s Sovriad (simeprevir), and Merck's ($MRK) Vanihep (vaniprevir).

Related to the review, PMDA posted a notice from BMS warning that a suspected reactivation of hepatitis B virus following the use of Daklinza and Sunvepra caused hepatic dysfunction, including one death.

On the PMDA notice, BMS called on doctors to send patients for hepatitis B virus marker tests prior to treatment.

A similar review is being conducted by the EMA, which began back in March. The agency has recently extended its review to also look at the risk of liver cancer (hepatocellular carcinoma) coming back in patients who were treated with direct-acting antivirals for hepatitis C, after a study published in April suggested this may be the case. 

In a statement to FiercePharmaAsia, Janssen said: “[We] are aware of the recently initiated review of Direct Acting Antivirals (DAAs) as a treatment for hepatitis C being conducted by the Pharmaceuticals and Medical Devices Agency (PMDA) in Japan. Simeprevir is one of the treatments currently undergoing the review procedure by the EMA and PMDA.  We believe that the safety of our medicines is paramount and we remain fully cooperative with both of these reviews.”

Meanwhile, BMS told FiercePharmaAsia: “The DAAs are indicated to treat hepatitis C; the observed cases of HBV reactivation have occurred in HCV patients who also have a history of HBV infection. 

“Reports of HBV reactivation are not specific to the DAA regimens; HBV reactivation also has been observed in the past among some HCV patients treated with interferon-based regimens.

"At Bristol-Myers Squibb, patient safety is our paramount concern. In conjunction with the PDMA/MHLW ongoing review, we have notified Japan healthcare providers that HBV reactivation has been reported in some patients treated with the DUAL (daclatasvir/asunaprevir) regimen.  In July 2014, DUAL was the first all-oral HCV regimen approved in Japan; healthcare providers in Japan have used it to treat more than 50,000 HCV patients.”

- here's the PMDA release