November 5, 2013

Initial Evaluation of the Sofosbuvir Compassionate Use Program for Patients with Severe Recurrent HCV Following Liver Transplantation

Dr. Xavier Forns


Disclosure: X. Forns: Gilead, Janssen, MSD; R.J. Fontana: Gilead, GSK, Tibotec, Vertex; D. Moonka; Gilead; J.G. McHutchison, W.T. Symonds, J. Denning, P. Chang, and V. Kivett are employees of and own stock in Gilead; L. McNair: Gilead; M. Shiffman: Gilead, Abbott, Achillion, Bayer, Beckman-Colter, BMS, Boehringer Ingelheim, Gen-Probe, GlobeImmune, GSK, Idenix, Intercept, Janssen, Merck, Mochida, Novartis, Roche/Genentech, Salix, Vertex; M. Charlton: Gilead, AbbVie, Biotest, BMS, Genentech, Novartis, Vertex.

CURRENT DESCRIPTORS: S06. HCV Therapy and Trials: New Agents (phase 2 -3)
SESSION TITLE: HCV Therapeutics: New Agents
ABSTRACT FINAL ID: Initial Evaluation of the Sofosbuvir Compassionate Use Program for Patients with Severe Recurrent HCV Following Liver Transplantation

AUTHOR/INSTITUTIONS: X. Forns, Liver Unit, Hospital Clinic, Barcelona, SPAIN|R.J. Fontana, University of Michigan, Ann Arbor, Michigan, UNITED STATES|D. Moonka, Henry Ford Health System, Detroit, Michigan, UNITED STATES|J.G. McHutchison, W.T. Symonds, J.M. Denning
SPONSORSHIP: Gilead Sciences, Inc.

Background: Patients with severe, recurrent hepatitis C (HCV) after liver transplantation (LT), who have either failed to respond to or are unable to tolerate antiviral therapies, have no effective treatment options. The polymerase inhibitor sofosbuvir (SOF) has been shown to be effective in combination with ribavirin (RBV), with or without peginterferon (PEG), in patients with HCV infection of all genotypes (GT).

Methods: SOF was provided in an IRB-approved compassionate use protocol (eIND or expanded access protocol) to treat patients with severe recurrent HCV infection following LT, including patients with fibrosing cholestatic hepatitis (FCH). The regimen included SOF 400 mg/day for up to 48 weeks, with appropriate doses of RBV and/or PEG at the physician’s discretion. Treating physicians provide periodic updates of clinical status, lab tests, and serious adverse events (SAEs).

Results: As of APR2013, 115 patients have been approved for compassionate use and 63 have started treatment. Of these, 45 have received ≥4 weeks of a SOF-containing regimen (36 SOF + RBV, 9 SOF+PEG/RBV). Baseline features of these 45 patients were: 33 GT1, 5 GT3, 7 other GTs; 29% female; mean age 55 years; mean baseline bilirubin 6.0 mg/dL (range 0.4-25.8) albumin 3.1 g/dL (2.0-4.8), INR 1.26 (0.96-2.07) and platelets 103 x 103/uL (27-316 x 103). Nineteen of the 45 (42%) had histologically-documented FCH. At week 4 of therapy, 28 of 36 patients (78%) who had reported HCV RNA levels were less than the limit of detection or quantification and 2 patients who received only 12 weeks of treatment have achieved SVR 12. The clinical condition of 32 of the 45 patients (71%) rapidly improved according to investigators’ narratives (eg, normalization of ALT and/or bilirubin levels, resolution of ascites which had been refractory to diuretics or requiring paracentesis, resolution/improvement of encephalopathy, increased muscle mass) within 1-4 weeks after the start of treatment. Another six patients (13%) were reported to have stabilized from their prior decompensation. Seven patients (16%) died after initiating therapy, with all deaths attributed to progression of liver disease or associated complications. Forty-seven SAEs have been reported in 23 patients. None were attributed to study drug.


Conclusions: In patients with severe post-LT HCV recurrence, a compassionate use regimen containing SOF and RBV (with or without PEG) has been well-tolerated and has demonstrated strong antiviral activity. The SOF-based regimen has resulted in notable clinical improvement and/or disease stabilization in many patients. Results will be updated at the time of presentation.


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