Gilead two-drug hep C combination cures 94% of genotype 1 patients in 8 weeks

A two-drug combination of sofosbuvir and ledipasvir cured 94% of previously untreated patients with genotype 1 hepatitis C infection after 8 weeks, without the need for ribavirin, Gilead Sciences announced on Wednesday.

The results released on 18 December come from one of three trials of the combination, ION-3. Two other studies tested the combination for longer periods and with previously untreated and treatment-experienced patients, and showed similarly high cure rates after 12 or 24 weeks of treatment, with or without ribavirin.

Gilead Sciences said that the very high cure rates observed in the studies mean that it will be possible to speed up registration plans for the combination. The company now plans to submit a licensing application in the first quarter of 2014, which means that the combination could receive marketing approval in the United States in the final quarter of 2014.

Sofosbuvir, a nucleotide polymerase inhibitor recently approved in the United States and European Union, was paired with ledipasvir, an NS5a inhibitor, in three studies testing different durations of treatment in various populations. The drugs were administered as a single pill once a day.

The ION-1 study compared 12 and 24 weeks of treatment with sofosbuvir and ledipasvir, with and without ribavirin, in previously untreated patients with genotype 1 hepatitis C infection. Approximately 15% had liver cirrhosis.

The ION-2 study compared 8, 12 and 24 weeks of treatment with sofosbuvir and ledipasvir, with and without ribavirin, in treatment-experienced patients with genotype 1 infection who had experienced failure of previous triple therapy with pegylated interferon, ribavirin and a protease inihbitor. Approximately 20% had cirrhosis.

The ION-3 study compared 8 and 12 weeks of treatment with sofosbuvir and ledipasvir without ribavirin, with 12 weeks of treatment with sofosbuvir and ledipasvir with ribavirin. All patients in this study were previously untreated and had genotype 1 infection. None had cirrhosis.

Gilead released 8- and 12-week results of ION 1, 2 and 3. The 24-week results of ION-1 will be released in the first quarter of 2014.

In the study arms released to date, 4.1% of study participants failed to achieve sustained virological response at 12 weeks post-treatment (SVR12). Of these, just over half (36 patients out of 62, or 2.4 percent of all participants, experienced virologic failure: 35 due to relapse and only one patient due to on-treatment breakthrough (this patient was non-adherent to therapy). Twenty-six patients (1.7%) were lost to follow-up or withdrew consent.

A more detailed breakdown of performance of each regimen and treatment duration in patients with cirrhosis will be reported at a future scientific meeting.

Gilead Sciences said that the ribavirin-sparing combination was better tolerated: anaemia, a common side-effect of ribavirin, was reported in 9.2% of patients who received ribavirin compared to 0.5% of patients who received sofosbuvir and ledipasvir without ribavirin. The most frequent side-effects of sofosbuvir and ledipasvir were headache and fatigue.

The results of these studies will pose a significant challenge to other developers of interferon-free combinations for the treatment of hepatitis C. An eight-week treatment course with two drugs will compare favourably in the eyes of many patients and physicians with a longer duration of treatment, although a major US pharmaceutical benefits company, which negotiates process on behalf of insurers and managed care organisations has warned that it may only pay for more expensive hepatitis C drugs if they are more effective. Convenience of dosing may not be enough to justify a higher price.