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HIV and Hepatitis.com Coverage of the
45th Annual Meeting of the European
Association for the Study of the Liver (EASL 2010)

April 14 - 18, 2010, Vienna, Austria

Controlled Release Interferon (Locteron) Every 2 Weeks Works as Well as Pegylated Interferon but with Fewer Side Effects

SUMMARY: A controlled-release formulation of interferon alfa-2b (Locteron), in combination with ribavirin, produced hepatitis C virus (HCV) suppression similar to that of pegylated interferon plus ribavirin over 12 weeks, according to 3 studies presented at the 45th Annual Meeting of the European Association for the Study of the Liver (EASL 2010) last month in Vienna. While similar proportions of patients achieved undetectable HCV viral load, those taking Locteron reported fewer flu-like side effects.

By Liz Highleyman

As part of standard therapy for chronic hepatitis C, pegylated interferon is administered once weekly along with daily ribavirin. Locteron, which is being developed by Biolex under a license from OctoPlus, is a microsphere-based controlled-release recombinant formulation of interferon alfa-2b that lasts longer in the body and can be taken once every 2 weeks. Previous research has shown that Locteron's trough concentration (lowest level) between doses maintained adequate antiviral activity.

In the open-label Phase 2b 480 Study, presented as an oral late-breaker at EASL, Z. Krastev and colleagues enrolled 74 treatment-naive genotype 1 chronic hepatitis C patients with compensated liver disease:

Panel A: 42 patients in Romania and Bulgaria (6-week data; 12 weeks not yet analyzed);
Panel B: 32 patients in Israel (12-week data).

Participants were randomly assigned to receive 480 mcg Locteron once every 2 weeks or 1.5 mcg/kg pegylated interferon alfa-2b (PegIntron) once weekly, both in combination with weight-adjusted ribavirin, for 12 weeks.

6-week data from Panel A showed that HCV viral load declined faster in the Loceteron arm compared with the pegylated interferon arm, with mean reductions of about 4 and 2 log, respectively, and about 40% and 5%, respectively, achieving undetectable HCV RNA.
At 12 weeks, according to data from Panel B, Locetron was non-inferior to pegylated interferon, with average viral load reductions of about 4 log and about 60% with undetectable HCV RNA in both arms.
Rates of serious adverse events were similar in both arms for both patient panels.
In Panel A, participants receiving Locteron reported about one third as many cumulative flu-like symptoms (headache, chills, fever, muscle or joint pain) than pegylated interferon recipients, but numbers were similar in the 2 arms of Panel B.
Hematological (blood) abnormalities including neutropenia (low neutrophil count) occurred infrequently in both arms and were generally mild-to-moderate.
While the overall frequency of injection site reactions was similar, Locteron recipients in Panel A were more likely than pegylated interferon recipients to report indurations (hard swelling).

E. Lawitz and colleagues presented a poster describing findings from the Phase 2b SELECT-2 trial, in which 116 treatment-naive genotype 1 chronic hepatitis C patients from the U.S. and Europe were randomly assigned to received once-weekly pegylated interferon or Locteron every 2 weeks at doses of 320 mcg, 480 mcg, or 640 mcg, all with weight-based ribavirin, for 48 weeks. The researchers monitored changes in HCV RNA and flu-like symptoms, based on patient self-reports using an Internet interface.

Through 36 weeks of treatment, mean HCV RNA decreases were similar in the 640 mcg and 480 mcg Locteron arms and in the pegylated interferon arm.
Patients receiving the 320 mcg Locteron dose eventually achieved a similar decrease, but viral decline was slower at earlier time points.
At week 12, rates of undetectable HCV RNA in the 640 mcg, 480 mcg, and 320 mcg Locteron arms and the pegylated interferon arm were 41%, 38%, 39%, and 40%, respectively (not a significant difference).
Undetectable rates were also similar at week 36, at 52%, 41%, 46%, and 50%, respectively.
After 36 weeks, participants in all 3 Locteron arms reported 65% fewer flu-like symptoms compared with those in the pegylated interferon arm.
Serious adverse events were uncommon in all arms.
Patients taking 480 mcg or 640 mcg Locteron reported higher rates of mild-to-moderate white blood cell and platelet loss, but this did not lead to more treatment discontinuations.

Finally, W. Long from Biolex and colleagues presented another poster describing findings from the EMPOWER study, which included 133 participants total from the 480 Study and the 480 mcg dose arm of SELECT-2. This provided a large enough group to test the hypothesis that Locteron would cause fewer flu-like symptoms than pegylated interferon; the analysis had 85% power to detect a 50% reduction in such symptoms.

Again, HCV RNA decreased somewhat more rapidly with Locteron, but comparable percentages achieved undetectable viral load by week 12.
Locteron recipients reported approximately half as many flu-like symptoms as those taking pegylated interferon.
Locteron recipients also reported missing fewer days of work.
Locteron recipients again experienced higher rates of mild-to-moderate white blood cell and platelet loss, while pegylated interferon recipients were more likely to experience mild-to-moderate anemia; however, no severe hematological side effects were observed with either drug.

Investigator affiliations:

Krastev study: Clinic of Gastroenterology, UMHAT St. Ivan Rilski, Sofia, Bulgaria; UMHAT St. Marina, Varna, Bulgaria; UMHAT Alexandrovska, Sofia, Bulgaria; Biolex Therapeutics, Pittsboro, NC; Medical Institute Ministry of Interior, UMHAT Queen Giovanna - ISUL EAD, Sofia, Bulgaria; Institute of Infectious Diseases, Prof. Dr. Matei Bals, Bucharest, Romania; Infectious Diseases, Victor Babes Clinical Hospital Craiova, Craiova, Romania; Internal Medicine, Nephrology Center, Fundeni Clinical Institute, Bucharest, Romania.

Long study: Biolex Therapeutics, Pittsboro, NC; Military Medical Academy, UMHAT Alexandrovska, Sofia, Bulgaria; UMHAT St. Marina, Varna, Bulgaria; UMHAT St. Ivan Rilski, Bulgaria; UMHAT Queen Giovanna - ISUL EAD, Bulgaria; Tokuda Hospital, Sofia, Bulgaria; Alamo Medical Research, San Antonio, TX; Inova Health Systems, Falls Church, VA; The Liver Institute at Methodist Dallas, Dallas, TX; Carmel Medical Center, Haifa, Israel; Holy Family Hospital Nazareth, Israel; Rabin Medical Center, Petah-Tikva, Israel; Rebekah Ziv Medical Center, Zefat, Israel; Sourasky Medical Center, Tel Aviv, Israel.

Lawitz study: Alamo Medical Research, San Antonio, TX; Inova Health Systems, Falls Church, VA; Study Site, Chula Vista, CA; Biolex Therapeutics, Pittsboro, NC; UMHAT St. Ivan Rilski, Bulgaria; UMHAT Alexandrovska; Sofia, Bulgaria; Military Medical Academy, Sofia, Bulgaria.

5/18/10

References

Z Krastev, I Kotzev, K Tchernev, and others. Randomized, open-label, 12-week comparison of controlled-release interferon alpha2b + ribavirin vs pegylated-interferon alpha2b + ribavirin in treatment-naive genotype 1 hepatitis C: 4 week results from 480 Study (Panel A). 45th Annual Meeting of the European Association for the Study of the Liver (EASL 2010). Vienna, Austria. April 14-18, 2010. (Abstract 58).

WA Long, D Takov, K Tchernev, and others. Q2week controlled-release-interferon-alpha2b + ribavrin reduces flu-like symptoms >50% and provides equivalent efficacy in comparison to weekly pegylated-interferon-alpha2b + ribavirin in treatment-naive-genotype-1-chronic-hepatitis-C: results from EMPOWER, a randomized-open-label-12-week-comparison in 133 patients. 45th Annual Meeting of the European Association for the Study of the Liver (EASL 2010). Vienna, Austria. April 14-18, 2010. (Abstract).

E Lawitz, Z Younoss, P Mehra, and others. Early viral response of controlled-release interferon alpha2b and ribavirin vs. pegylated-interferon alpha2b and ribavirin in treatment-naive genotype1 hepatitis C: 12 week results (SELECT-2 trial). 45th Annual Meeting of the European Association for the Study of the Liver (EASL 2010). Vienna, Austria. April 14-18, 2010. (Abstract).

Other Sources

Biolex Announces Presentation at EASL of Interim Results from SELECT-2 Phase 2b trial of Locteron in Chronic Hepatitis C. Press release. April 15, 2010.

Biolex Announces Presentation at EASL of Interim Results from EMPOWER Phase 2b trial of Locteron in Chronic Hepatitis C. Press release. April 16, 2010.

OctoPlus N.V. OctoPlus Announces Publication of Positive Locteron Interim Phase IIb Data. Press release. March 16, 2010.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 



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