Biolex Therapeutics, Inc. has announced that results demonstrating reduced rates of depression from its SELECT-2 Phase 2b trial of Locteron® for the treatment of hepatitis C are being presented at the 46th Annual Meeting of the European Association for the Study of the Liver (EASL) in Berlin, Germany.
In SELECT-2, patients treated with Locteron within the expected commercial dose range experienced substantially lower rates of depression and depressive symptoms than patients treated with the PEG-Intron® control. Locteron, the only controlled-release interferon alpha, is designed to offer key tolerability and dosing advantages over currently marketed pegylated interferons and serve as a core component of new combination therapies as the treatment of hepatitis C evolves to triple- and quad-drug regimens.
In a survey of hepatitis C patients published in the Journal of Viral Hepatitis in 2010, depression was cited as the number one adverse event impacting patient adherence to treatment, and studies have shown that patients who develop depression during treatment have a reduced chance of achieving a cure.
The expected progression of treatment for hepatitis C to triple and quad regimens with potentially shorter durations of treatment are unlikely to eliminate the problem of depression as the SELECT-2 results presented today show that the majority of all episodes of depression occur by the 12th week of treatment.
Locteron is administered once every other week and requires half as many injections as the currently marketed pegylated interferons, each of which are injected once per week. In SELECT-2, three different doses of Locteron were studied (320, 480 and 640 µg).
All three doses of Locteron in SELECT-2 demonstrated viral kinetics and sustained virologic response (SVR) rates that were comparable with or exceeded the PEG-Intron control while also achieving a statistically significant reduction in flu-like adverse events and lower use of concomitant medications.
The Company expects the commercial dose of Locteron to be in the 320 to 480 µg range as the SVR rates for these two doses were comparable with or exceeded the control, and the tolerability advantages (including lower discontinuation rates due to adverse events) were greatest within this dose range.
In SELECT-2, depression was assessed by two methods, including patient self reporting using a validated instrument and adverse event assessments performed by medical personnel at the clinical sites during weekly visits by the patients. The SELECT-2 results demonstrated that patients experienced depression early in the study, with 75% of cases occurring within the first 12 weeks of the trial under each of the reporting methodologies.
Under both reporting methodologies, depression was less frequent for the Locteron doses encompassing the expected commercial dose range compared to the PEG-Intron control.
Throughout the 48 weeks of treatment in SELECT-2, patients self reported their status using the Beck Depression Inventory (BDI), one of the most widely used instruments for measuring the severity of depression. Higher BDI scores indicate more severe depressive symptoms.
Mean BDI scores peaked by week 12 of treatment for all Locteron doses and for the PEG-Intron control group. The increase in peak mean BDI scores was substantially less for all three Locteron doses compared to the PEG-Intron group. In addition, the results demonstrated that fewer patients reported scores greater than 16 using the BDI (the threshold for mild depression) in the 320 and 480 µg Locteron dose groups compared to the PEG-Intron group.