Albinterferon (Zalbin™, Human Genome Sciences) is a longeracting IFN, allowing for once or twice/month dosing schedule. It consists of IFN alfa-2b genetically fused to recombinant human albumin. Several unique features of albumin make it an ideal candidate for integration into a drug-design platform, including its unusually long half-life (~19 days), wide distribution, negligible potential for confounding enzymatic or immunological function and its physiological role as a carrier of blood substances. The pharmacodynamic attributes of albinterferon, which include the maintenance of viral suppression across a longer dosing interval, might reduce viral rebounds, while also improving patient’s compliance. In phase III trials, in patients with genotype 1 CHC, albinterferon (900 μg every 2 weeks) achieved noninferiority compared with PegIFN alfa-2a, indicating that the two drugs are equivalent (Nelson 2009). Albinterferon was also administered with good results in combination with RBV in non-responders to prior IFN therapy and is evaluated for the treatment of HIV/HCV coinfected patients. However, the preliminary FDA evaluation indicates that the licensing of this dosing regimen is unlikely, due to the unfavorable risk-benefit profile, mainly caused by slightly increased rates of serious pulmonary AEs, coughing and alopecia compared to PegIFN. Development and testing of once per month dosage is undergoing.
Controlled-release recombinant interferon alfa-2b formulations were designed to improve the pharmacokinetic parameters, in order to maintain continuous drug levels and consequently minimize side effects as compared to current IFNs. Locteron® (Biolex Therapeutics/OctoPlus) is a recombinant nonglycosylate IFN alfa-2b produced in polyether-ester microspheres. This steady controlled-release formulation avoids fluctuation in IFN levels. A pilot study reported that after injection of 320 μg Locteron®, the concentration of serum IFN remained elevated through 14 days (De Leede 2008). Locteron® can be administered twice monthly, with its trough concentration between doses maintaining adequate antiviral activity. Preliminary results of phase IIb studies, showed that in treatment-naive patients, Locteron®, in combination with RBV, produced similar viral suppression to that of PegIFN/RBV, with fewer flu-like side effects and substantially lower rates of depression. Viagra india
IFN XL (Flamel Technologies) is an extra-long controlledrelease formulation of recombinant IFN alfa-2b, based on the nanoparticles Medusa delivery system, designed for the tailored delivery of fully-active proteins. Basically this is a nanoparticle polymer with embedded IFN, which has a slow, sustained release with increased efficacy. In a phase I study, IFN XL induced greater reduction in VL after two weeks with fewer AEs compared to PegIFN (Soriano 2009). A phase IIa study designed to evaluate IFN XL in combination with RBV in naive and previous G1 HCV non-responders to SoC is ongoing.
Omega interferon (Intarcia Therapeutics, Inc.) is a type 1 interferon delivered with an osmotic mini-pump implanted subcutaneously. Omega DUROS® is a drug delivery system that stabilizes therapeutic proteins, delivering a continuous dose of omega interferon at a constant rate for 3 months.