Showing posts with label Locteron. Show all posts
Showing posts with label Locteron. Show all posts
Wednesday, July 11, 2012
Biolex Therapeutics files for $38M bankruptcy
Posted 7-6-2012 on Bizjournals.com. Biolex Therapeutics has filed for bankruptcy, which effectively terminates the development of it's controlled release alpha interferon-2b and presumably it's relationship with OctoPlus as a result. Boo.
Biolex Therapeutics files for $38M bankruptcy
Triangle Business Journal by Chris Bagley, Staff Writer
Date: Friday, July 6, 2012, 8:07am EDT
Chris Bagley
Staff Writer- Triangle Business Journal
Biolex Therapeutics Inc. has filed for bankruptcy liquidation, marking an inauspicious end to $190 million that investors had poured into the Pittsboro-based company since its founding in 1997.
The company's Chapter 7 filing on July 3 cited $38 million in liabilities, including nearly $5 million owed to Intersouth Partners of Durham. Other large creditors include Clarus Lifesciences, a venture capital firm with offices in the San Francisco and Boston areas, which is owed $8.4 million, and an investment arm of the pharmaceutical giant Johnson & Johnson, which has a $3.8 million claim, according to Biolex's filing.
Clarus, Intersouth and the J&J fund are also listed as the company's largest, second-largest and third-largest shareholders, with 27 percent, 13 percent and 11 percent stakes, respectively.
Biolex's filing showed just $803,000 in assets.
Biolex recently had faced an increasingly daunting task of raising money to develop its Locteron drug for hepatitis C. The company had touted the drug as likely to have milder side effects and more convenient dosing than existing hepatitis C treatments.
Biolex shrank from 70 employees at its peak to about 13 in February. CFO Dale Sander told Triangle Business Journal that month that the company was considering a sale as one of several alternatives to continue Locteron's development.
Like other varieties of hepatitis, hep C can cause fatigue and loss of appetite or no symptoms at all and can ultimately lead to cirrhosis. The lettered varieties of hepatitis are all brought about by different viruses, and the drugs for treating them also vary.
Chris Bagley covers the legal-services industry, transportation and utilities. Follow him on Twitter @cbagley.
Thursday, March 31, 2011
Locteron beats it's pegylated cousin in 72 week SELECT 2 results at EASL...
I know the Pharmasset folks are bullish about a interferon-free drug combo to treat HCV - actually, we ALL are, but until we have SVR data from that particular combination and others like it in development, interferon is here to stay. Biolex (who features ex-Vertex CCO Kurt Graves as it's Executive Chairman of the Board) is the entity here in the States that is developing Locteron. The deal with Locteron is that it's a Peg-less PegIntron with a sexy new controlled release technology that allows it to be dosed every other week. Added benefits are a nice reduction in flu-like side-effects and interferon-related depression. Results of it's Phase IIb study, SELECT-2, comparing it to Pegintron look pretty good. Locteron maintains and/or beats it's pegylated cousin in the SVR department (SVR 41% (640 μg); 34% (480 μg); 36% (320 μg); 33% (Pegintron))while chopping the number of shots in half and reducing AE's. The big problem at this point isn't the threat of an interferon-free HCV drug combo, but lack of data with a DAA. I'm not schooled in Biolex, but I'm sure that's the company's hope going forward. Or it may just file with a DAA-less indication if the Phase III data and competitive environment look promising enough. Either way, the thought of a more user-friendly interferon is pretty enticing. Hopefully, investors will feel the same way.
OctoPlus N.V. ("OctoPlus" or the "Company") (Euronext: OCTO) announces that its licensee Biolex Therapeutics will present today final results from the Locteron® Phase IIb clinical study at the 46th Annual Meeting of the European Association for the Study of the Liver (EASL) in Berlin, Germany. These data highlight important tolerability advantages of Locteron versus current HCV treatments.
Jan Egberts, CEO of OctoPlus, comments: "These positive final results from the Phase IIb clinical study with Locteron further confirm the long term benefits of Locteron's controlled release mechanism. Our PolyActive technology has enabled the development of an interferon alpha with a significantly improved side effect profile, achieving both a 50% reduction in flu-like adverse events and substantially lower rates of depression compared to conventional interferon treatments. In combination with its reduced injection frequency, these benefits clearly position Locteron as the interferon of choice for future hepatitis C treatments."
The following information was taken directly from Biolex' press release (see www.biolex.com).
Biolex announces that final 72-week results from its SELECT-2 Phase 2b trial of Locteron® for the treatment of hepatitis C are being presented today at the 46th Annual Meeting of the European Association for the Study of the Liver (EASL) in Berlin, Germany. Data presented today show that Locteron achieved the SELECT-2 study objectives by demonstrating viral kinetics and response rates that were comparable with or exceeded the PEG-Intron® control while also achieving a statistically significant reduction in flu-like adverse events, reduced rates of depression, lower use of concomitant medications and a reduced rate of discontinuation due to adverse events. Locteron, the only controlled-release interferon alpha, is designed to offer key tolerability and dosing advantages over currently marketed interferons and serve as a core component of new combination therapies as the treatment of hepatitis C evolves to triple- and quad-drug regimens.
Locteron dosing convenience and efficacy
Locteron is administered once every other week and requires half as many injections as the currently marketed interferons, each of which are injected once per week. In SELECT-2, the sustained virologic response rate (SVR) for each of the three Locteron doses studied was comparable with or exceeded the response rate for the PEG-Intron control as outlined in the table below.
Click on the link for the press release including tables.
OctoPlus N.V. ("OctoPlus" or the "Company") (Euronext: OCTO) announces that its licensee Biolex Therapeutics will present today final results from the Locteron® Phase IIb clinical study at the 46th Annual Meeting of the European Association for the Study of the Liver (EASL) in Berlin, Germany. These data highlight important tolerability advantages of Locteron versus current HCV treatments.
Jan Egberts, CEO of OctoPlus, comments: "These positive final results from the Phase IIb clinical study with Locteron further confirm the long term benefits of Locteron's controlled release mechanism. Our PolyActive technology has enabled the development of an interferon alpha with a significantly improved side effect profile, achieving both a 50% reduction in flu-like adverse events and substantially lower rates of depression compared to conventional interferon treatments. In combination with its reduced injection frequency, these benefits clearly position Locteron as the interferon of choice for future hepatitis C treatments."
The following information was taken directly from Biolex' press release (see www.biolex.com).
Biolex announces that final 72-week results from its SELECT-2 Phase 2b trial of Locteron® for the treatment of hepatitis C are being presented today at the 46th Annual Meeting of the European Association for the Study of the Liver (EASL) in Berlin, Germany. Data presented today show that Locteron achieved the SELECT-2 study objectives by demonstrating viral kinetics and response rates that were comparable with or exceeded the PEG-Intron® control while also achieving a statistically significant reduction in flu-like adverse events, reduced rates of depression, lower use of concomitant medications and a reduced rate of discontinuation due to adverse events. Locteron, the only controlled-release interferon alpha, is designed to offer key tolerability and dosing advantages over currently marketed interferons and serve as a core component of new combination therapies as the treatment of hepatitis C evolves to triple- and quad-drug regimens.
Locteron dosing convenience and efficacy
Locteron is administered once every other week and requires half as many injections as the currently marketed interferons, each of which are injected once per week. In SELECT-2, the sustained virologic response rate (SVR) for each of the three Locteron doses studied was comparable with or exceeded the response rate for the PEG-Intron control as outlined in the table below.
Click on the link for the press release including tables.
Monday, November 22, 2010
Electronic patient diaries vs on-site side-effect reports: A case study featuring Locteron
Very nice article here on the power of ePRO (Electronic patient diaries) vs on-site patient reports to the physician on adverse events. It appears that evolving technology is helping to undermine the incidence of under-reporting of adverse events. This particular example adds credibility to Biolex's Locteron (Interferon Lambda) Phase IIb trial.
Biolex reveals ePRO surprise; selection process
By George Miller
Created Nov 22 2010 - 1:32am
Biolex CEO Jan Turek notes something unforeseen in the ePRO element of the company's recent trial of a hepatitis C treatment: The degree of difference in reports of side-effect severity in the weekly case report forms completed by clinicians versus the daily ePRO accounts of trial volunteers. Some 85 percent of reports by doctors describe mild side-effects, whereas the volunteers reporting electronically most often rated the severity as moderate or severe.
It was "a surprise to us and our key opinion leaders," Turek says in a phone interview. "It brought home the need for patient reports to be taken more seriously."
Findings from the trial do, however, reflect commonality between the reporting media types in the trial's side-effect result--a statistically significant 40 to 50 percent drop in the frequency and severity of flu-like symptoms for the 480-microgram dose of Biolex's Locteron compared with the PEG-Intron control.
Researchers were tracking the flu-like symptoms as a means of comparing the treatments in the Phase IIb trial. "What you measure drives how you gather data," explains Biolex CFO Dale Sander in the interview. Investigators as well as the key opinion leaders thought ePRO fit the bill. The side-effect data collected through the ePRO system are considered supplemental to the reports taken during weekly clinic visits.
Biolex used an ePRO system from Unithink [1] in the global trial. Among the key factors in its choice was the system's ability to instantaneously receive reports and capture them in the EDC system, rather than a set-up that involves reporting and later docking and uploading, says Amy Rigney, clinical ops director. "That was a differentiator."
Another was ease of patient use. "We wanted to be sure the ePRO system was programmed for several languages." Also, ePRO/EDC set-up allowed trial volunteers to report side effects via cellphone or laptop. "It didn't force the issue one way or the other," she says.
Biolex evaluated available ePRO systems in 2008 and had several months of discussions involving investigators, the data management group, and the clinical group. The company's IT team participated throughout the process to ensure overall systems compatibility, says Rigney, including the final selection of Unithink.
"Volunteers' recall and ability to assess a side effect is better when they are entering the data simultaneous with the event," she says. "You're getting it unfiltered."
Biolex reveals ePRO surprise; selection process
By George Miller
Created Nov 22 2010 - 1:32am
Biolex CEO Jan Turek notes something unforeseen in the ePRO element of the company's recent trial of a hepatitis C treatment: The degree of difference in reports of side-effect severity in the weekly case report forms completed by clinicians versus the daily ePRO accounts of trial volunteers. Some 85 percent of reports by doctors describe mild side-effects, whereas the volunteers reporting electronically most often rated the severity as moderate or severe.
It was "a surprise to us and our key opinion leaders," Turek says in a phone interview. "It brought home the need for patient reports to be taken more seriously."
Findings from the trial do, however, reflect commonality between the reporting media types in the trial's side-effect result--a statistically significant 40 to 50 percent drop in the frequency and severity of flu-like symptoms for the 480-microgram dose of Biolex's Locteron compared with the PEG-Intron control.
Researchers were tracking the flu-like symptoms as a means of comparing the treatments in the Phase IIb trial. "What you measure drives how you gather data," explains Biolex CFO Dale Sander in the interview. Investigators as well as the key opinion leaders thought ePRO fit the bill. The side-effect data collected through the ePRO system are considered supplemental to the reports taken during weekly clinic visits.
Biolex used an ePRO system from Unithink [1] in the global trial. Among the key factors in its choice was the system's ability to instantaneously receive reports and capture them in the EDC system, rather than a set-up that involves reporting and later docking and uploading, says Amy Rigney, clinical ops director. "That was a differentiator."
Another was ease of patient use. "We wanted to be sure the ePRO system was programmed for several languages." Also, ePRO/EDC set-up allowed trial volunteers to report side effects via cellphone or laptop. "It didn't force the issue one way or the other," she says.
Biolex evaluated available ePRO systems in 2008 and had several months of discussions involving investigators, the data management group, and the clinical group. The company's IT team participated throughout the process to ensure overall systems compatibility, says Rigney, including the final selection of Unithink.
"Volunteers' recall and ability to assess a side effect is better when they are entering the data simultaneous with the event," she says. "You're getting it unfiltered."
Tuesday, November 2, 2010
Biolex presents positive tolerability data of Locteron vs Peg-Intron at AASLD...
Market Wire - Nov. 01, 2010
PITTSBORO, NC -- (MARKET WIRE) -- 11/01/10 -- Biolex Therapeutics, Inc. today announced positive results from two Phase 2b trials further demonstrating the strong anti-viral response and tolerability advantages of the 480 µg dose of Locteron® in the treatment of hepatitis C. In the Phase 2b trials, patients directly reported flu-like adverse events on a daily basis through an electronic patient-reported outcome (ePRO) system, and the results demonstrated a statistically significant reduction in the frequency and severity of flu-like adverse events and reduced use of concomitant (analgesic/antipyretic) medications for patients treated with Locteron compared to patients treated with the PEG-Intron® control. Locteron, controlled-release interferon alpha 2b, is designed to offer key advantages compared to currently marketed interferons as a core component of combination therapies for the treatment of hepatitis C. These advantages include reduced flu-like symptoms, reduced rates of depression, and a less frequent dosing regimen with half the number of injections. The "EMPOWER" Phase 2b ePRO results will be presented today in a late-breaker session at the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston.
EMPOWER is a prospectively designed analysis of the combined results from two Phase 2b hepatitis C trials focusing on the 480 µg dose of Locteron (the middle dose of three Locteron doses evaluated in the two trials). Through 12 weeks of treatment, 50% of the patients in the Locteron 480 µg group achieved cEVR (undetectable HCV RNA) compared to 46% of the patients in the PEG-Intron group. As a result of its controlled-release mechanism, Locteron achieved strong efficacy results while being dosed half as frequently as PEG-Intron.
The AASLD presentation today includes for the first time results from the ePRO adverse-event reporting system where patients directly recorded their flu-like adverse events on a daily basis, providing greater insight into the patients' real world experiences with these side effects and the impact on their daily activities. In addition to the self-reporting by patients with the ePRO system, flu-like adverse events were also recorded using traditional weekly adverse event assessments performed by the clinical sites. Flu-like adverse events were predefined to include arthralgia, chills, fever, headache, and myalgia.
A substantial reduction in flu-like adverse events for patients treated with Locteron compared to PEG-Intron was evident even in the first week after initiation of treatment and continued through the 12-week time point through which the ePRO system was utilized. The reduction in flu-like adverse events during the week after the first injection supports the hypothesis that the slower rise to Cmax provided by the controlled-release mechanism of Locteron contributes to the tolerability advantages seen in multiple clinical trials. A comparison of the flu-like adverse event reporting by the clinical sites and by ePRO provide independent confirmation of the substantial benefits Locteron provided in reducing these side effects as outlined in the table below:
Locteron Reduction in Flu-Like Adverse Events (Week 1)
---------------------------------------------------------
Total Events Moderate and Severe Events
---------------------------- ----------------------------
Clinical Site Patient (ePRO) Clinical Site Patient (ePRO)
Reporting Self-Reporting Reporting Self-Reporting
------------- -------------- ------------- --------------
Locteron Reduction 50% 51% 70% 39%
In Flu-Like Adverse Reduction Reduction Reduction Reduction
Events Compared to
PEG-Intron
"The ePRO results being presented for the first time today are robust and provide important insight into the impact that flu-like adverse events have on patients' daily lives," said Patrick Marcellin, MD, PhD, Professor of Hepatology at the University of Paris and Head of the Viral Hepatitis Research Unit in Hôpital Beaujon, Clichy. "Treatment of hepatitis C is likely to progress to triple and quad therapies in which interferons are combined with one or more direct-acting anti-viral drugs. Locteron's advantages with regards to flu-like adverse events, depression and dosing frequency have the potential to enhance the overall tolerability of, and patient adherence to, these future combinations."
Consistent with the reduction in flu-like adverse events, less than half as many Locteron patients used concomitant medications (analgesics and antipyretics) compared to the usage of these medications by PEG-Intron patients during the study period as detailed below.
Percentage of Patients Using
Concomitant Medications
-----------------------------------------
Locteron
480 µg PEG-Intron
-------------------- --------------------
Patients Using Analgesics 27% 59%
Patients Using Antipyretics 23% 49%
A comparison of the ePRO and clinic site reporting highlights the fact that flu-like adverse events may even be more important to patients than historically believed. The total flu-like adverse events reported directly by the patients using the ePRO system during the first 12 weeks of EMPOWER was more than four times greater than the total flu-like adverse events recorded by the clinical sites. Also of importance, patients rated 80% of their flu-like adverse events as moderate or severe in their ePRO reports, compared to the clinical site reporting in which only 13% of flu-like adverse events were rated as moderate or severe. Despite the apparent differences in sensitivity in the two adverse event reporting methods, the results from both the ePRO and weekly clinic visits independently confirm the reduction in flu-like adverse events for patients treated with Locteron compared to patients treated with PEG-Intron. Through the 12-weeks, the difference in flu-like adverse event counts was statistically significant when measured by both the ePRO and clinical site reporting methods (p < 0.001 for each).
The relevance of flu-like adverse events was highlighted in a survey of hepatitis C patients published in the Journal of Viral Hepatitis in June 2010 in which depression and flu-like symptoms were cited as the two most important adverse events impacting patient adherence to treatment. Last week Biolex reported 48-week results from its SELECT-2 Phase 2b trial of Locteron demonstrating substantial reductions in depression compared to PEG-Intron.
AASLD Presentation
The EMPOWER ePRO and clinical-site tolerability results will be presented today by the lead author, Walker Long, MD, Chief Medical Officer and Vice President, Drug Development, Biolex Therapeutics, in the form of a poster titled "Adverse Event Reporting During HCV Treatment Via Weekly Clinic Visits Substantially Underestimates Flu Frequency & Severity Compared to Daily ePRO: Results From 133 Patients in EMPOWER."
"The EMPOWER results are notable in that they show a statistically significant reduction of flu-like adverse events for Locteron confirmed by two sources, the clinical site assessments and the daily patient reporting of side effects through the ePRO System. The reductions in the percent of patients using analgesics and in overall analgesic use observed in the Locteron group provide additional support for improved tolerability on Locteron," said Dr. Long. "These results complement the positive results released last week from our SELECT-2 Phase 2b trial in which we showed statistically significant reductions in flu-like adverse events for three different Locteron doses, and substantial reductions in depression for the Locteron 480 and 320 µg doses."
About EMPOWER Study
The objective of the EMPOWER study was to test the hypothesis that the 480 µg dose of Locteron dosed once every two weeks reduces flu-like symptoms but retains equivalent efficacy compared to PEG-Intron (1.5 µg/kg, administered every week). The 133 patients in the EMPOWER study were enrolled in two contributing Phase 2b trials:
* SELECT-2, a Phase 2b dose-finding trial evaluating the 320, 480 or 640 µg doses of Locteron versus PEG-Intron.
* The 480 STUDY, a Phase 2b trial evaluating the 480 µg dose of Locteron versus PEG-Intron.
All patients in both trials were treatment-naïve-genotype-1 subjects with chronic hepatitis C, and all patients were also treated with weight-based ribavirin. A total of 30 sites participated in the two trials (14 sites in the US, 11 in Europe, and five in Israel).
Locteron Overview
Locteron, controlled-release interferon alpha 2b, is designed to offer key advantages compared to currently approved products, including reduced flu-like symptoms and rates of depression, and cutting in half the number of injections required. In contrast to Locteron, the currently approved products, Pegasys® and PEG-Intron, are immediate-release products that lack a controlled-release mechanism. The two-drug combination of interferon alpha and ribavirin serves as the current standard of care for the treatment of hepatitis C. The launch of the first direct-acting anti-viral (DAA) product, projected for 2011, will transform treatment of genotype-1 patients to a triple-drug therapy (interferon plus ribavirin plus DAA) and substantially raise cure rates. Other recent triple or quad drug combinations with interferon (including interferon plus ribavirin plus two DAA agents) have shown promise in early clinical testing, further solidifying the continued role of interferon in the treatment of hepatitis C. It is estimated that worldwide sales of interferon products for the treatment of hepatitis C will approach $6 billion by 2016.
Locteron incorporates an advanced controlled-release drug delivery technology that allows dosing once every two weeks, more convenient than Pegasys and PEG-Intron, each of which require dosing every week. More importantly, Locteron's controlled-release mechanism results in the gradual release of interferon alpha 2b to patients over the duration of two weeks and avoids the early peak plasma levels of the active interferon that characterize the pegylated interferons. This controlled-release mechanism is designed to reduce the frequency and severity of flu-like symptoms and depression commonly experienced by patients treated with pegylated interferons.
Locteron is an investigational therapeutic candidate and has not been approved for sale by the United States Food and Drug Administration or by any international regulatory agency.
PITTSBORO, NC -- (MARKET WIRE) -- 11/01/10 -- Biolex Therapeutics, Inc. today announced positive results from two Phase 2b trials further demonstrating the strong anti-viral response and tolerability advantages of the 480 µg dose of Locteron® in the treatment of hepatitis C. In the Phase 2b trials, patients directly reported flu-like adverse events on a daily basis through an electronic patient-reported outcome (ePRO) system, and the results demonstrated a statistically significant reduction in the frequency and severity of flu-like adverse events and reduced use of concomitant (analgesic/antipyretic) medications for patients treated with Locteron compared to patients treated with the PEG-Intron® control. Locteron, controlled-release interferon alpha 2b, is designed to offer key advantages compared to currently marketed interferons as a core component of combination therapies for the treatment of hepatitis C. These advantages include reduced flu-like symptoms, reduced rates of depression, and a less frequent dosing regimen with half the number of injections. The "EMPOWER" Phase 2b ePRO results will be presented today in a late-breaker session at the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston.
EMPOWER is a prospectively designed analysis of the combined results from two Phase 2b hepatitis C trials focusing on the 480 µg dose of Locteron (the middle dose of three Locteron doses evaluated in the two trials). Through 12 weeks of treatment, 50% of the patients in the Locteron 480 µg group achieved cEVR (undetectable HCV RNA) compared to 46% of the patients in the PEG-Intron group. As a result of its controlled-release mechanism, Locteron achieved strong efficacy results while being dosed half as frequently as PEG-Intron.
The AASLD presentation today includes for the first time results from the ePRO adverse-event reporting system where patients directly recorded their flu-like adverse events on a daily basis, providing greater insight into the patients' real world experiences with these side effects and the impact on their daily activities. In addition to the self-reporting by patients with the ePRO system, flu-like adverse events were also recorded using traditional weekly adverse event assessments performed by the clinical sites. Flu-like adverse events were predefined to include arthralgia, chills, fever, headache, and myalgia.
A substantial reduction in flu-like adverse events for patients treated with Locteron compared to PEG-Intron was evident even in the first week after initiation of treatment and continued through the 12-week time point through which the ePRO system was utilized. The reduction in flu-like adverse events during the week after the first injection supports the hypothesis that the slower rise to Cmax provided by the controlled-release mechanism of Locteron contributes to the tolerability advantages seen in multiple clinical trials. A comparison of the flu-like adverse event reporting by the clinical sites and by ePRO provide independent confirmation of the substantial benefits Locteron provided in reducing these side effects as outlined in the table below:
Locteron Reduction in Flu-Like Adverse Events (Week 1)
---------------------------------------------------------
Total Events Moderate and Severe Events
---------------------------- ----------------------------
Clinical Site Patient (ePRO) Clinical Site Patient (ePRO)
Reporting Self-Reporting Reporting Self-Reporting
------------- -------------- ------------- --------------
Locteron Reduction 50% 51% 70% 39%
In Flu-Like Adverse Reduction Reduction Reduction Reduction
Events Compared to
PEG-Intron
"The ePRO results being presented for the first time today are robust and provide important insight into the impact that flu-like adverse events have on patients' daily lives," said Patrick Marcellin, MD, PhD, Professor of Hepatology at the University of Paris and Head of the Viral Hepatitis Research Unit in Hôpital Beaujon, Clichy. "Treatment of hepatitis C is likely to progress to triple and quad therapies in which interferons are combined with one or more direct-acting anti-viral drugs. Locteron's advantages with regards to flu-like adverse events, depression and dosing frequency have the potential to enhance the overall tolerability of, and patient adherence to, these future combinations."
Consistent with the reduction in flu-like adverse events, less than half as many Locteron patients used concomitant medications (analgesics and antipyretics) compared to the usage of these medications by PEG-Intron patients during the study period as detailed below.
Percentage of Patients Using
Concomitant Medications
-----------------------------------------
Locteron
480 µg PEG-Intron
-------------------- --------------------
Patients Using Analgesics 27% 59%
Patients Using Antipyretics 23% 49%
A comparison of the ePRO and clinic site reporting highlights the fact that flu-like adverse events may even be more important to patients than historically believed. The total flu-like adverse events reported directly by the patients using the ePRO system during the first 12 weeks of EMPOWER was more than four times greater than the total flu-like adverse events recorded by the clinical sites. Also of importance, patients rated 80% of their flu-like adverse events as moderate or severe in their ePRO reports, compared to the clinical site reporting in which only 13% of flu-like adverse events were rated as moderate or severe. Despite the apparent differences in sensitivity in the two adverse event reporting methods, the results from both the ePRO and weekly clinic visits independently confirm the reduction in flu-like adverse events for patients treated with Locteron compared to patients treated with PEG-Intron. Through the 12-weeks, the difference in flu-like adverse event counts was statistically significant when measured by both the ePRO and clinical site reporting methods (p < 0.001 for each).
The relevance of flu-like adverse events was highlighted in a survey of hepatitis C patients published in the Journal of Viral Hepatitis in June 2010 in which depression and flu-like symptoms were cited as the two most important adverse events impacting patient adherence to treatment. Last week Biolex reported 48-week results from its SELECT-2 Phase 2b trial of Locteron demonstrating substantial reductions in depression compared to PEG-Intron.
AASLD Presentation
The EMPOWER ePRO and clinical-site tolerability results will be presented today by the lead author, Walker Long, MD, Chief Medical Officer and Vice President, Drug Development, Biolex Therapeutics, in the form of a poster titled "Adverse Event Reporting During HCV Treatment Via Weekly Clinic Visits Substantially Underestimates Flu Frequency & Severity Compared to Daily ePRO: Results From 133 Patients in EMPOWER."
"The EMPOWER results are notable in that they show a statistically significant reduction of flu-like adverse events for Locteron confirmed by two sources, the clinical site assessments and the daily patient reporting of side effects through the ePRO System. The reductions in the percent of patients using analgesics and in overall analgesic use observed in the Locteron group provide additional support for improved tolerability on Locteron," said Dr. Long. "These results complement the positive results released last week from our SELECT-2 Phase 2b trial in which we showed statistically significant reductions in flu-like adverse events for three different Locteron doses, and substantial reductions in depression for the Locteron 480 and 320 µg doses."
About EMPOWER Study
The objective of the EMPOWER study was to test the hypothesis that the 480 µg dose of Locteron dosed once every two weeks reduces flu-like symptoms but retains equivalent efficacy compared to PEG-Intron (1.5 µg/kg, administered every week). The 133 patients in the EMPOWER study were enrolled in two contributing Phase 2b trials:
* SELECT-2, a Phase 2b dose-finding trial evaluating the 320, 480 or 640 µg doses of Locteron versus PEG-Intron.
* The 480 STUDY, a Phase 2b trial evaluating the 480 µg dose of Locteron versus PEG-Intron.
All patients in both trials were treatment-naïve-genotype-1 subjects with chronic hepatitis C, and all patients were also treated with weight-based ribavirin. A total of 30 sites participated in the two trials (14 sites in the US, 11 in Europe, and five in Israel).
Locteron Overview
Locteron, controlled-release interferon alpha 2b, is designed to offer key advantages compared to currently approved products, including reduced flu-like symptoms and rates of depression, and cutting in half the number of injections required. In contrast to Locteron, the currently approved products, Pegasys® and PEG-Intron, are immediate-release products that lack a controlled-release mechanism. The two-drug combination of interferon alpha and ribavirin serves as the current standard of care for the treatment of hepatitis C. The launch of the first direct-acting anti-viral (DAA) product, projected for 2011, will transform treatment of genotype-1 patients to a triple-drug therapy (interferon plus ribavirin plus DAA) and substantially raise cure rates. Other recent triple or quad drug combinations with interferon (including interferon plus ribavirin plus two DAA agents) have shown promise in early clinical testing, further solidifying the continued role of interferon in the treatment of hepatitis C. It is estimated that worldwide sales of interferon products for the treatment of hepatitis C will approach $6 billion by 2016.
Locteron incorporates an advanced controlled-release drug delivery technology that allows dosing once every two weeks, more convenient than Pegasys and PEG-Intron, each of which require dosing every week. More importantly, Locteron's controlled-release mechanism results in the gradual release of interferon alpha 2b to patients over the duration of two weeks and avoids the early peak plasma levels of the active interferon that characterize the pegylated interferons. This controlled-release mechanism is designed to reduce the frequency and severity of flu-like symptoms and depression commonly experienced by patients treated with pegylated interferons.
Locteron is an investigational therapeutic candidate and has not been approved for sale by the United States Food and Drug Administration or by any international regulatory agency.
Thursday, October 28, 2010
Biolex announces Locteron SVR12 & safety/tolerability advantages in SELECT-2 trial..
Market Wire - Oct. 28, 2010
PITTSBORO, NC -- (MARKET WIRE) -- 10/28/10 -- Biolex Therapeutics, Inc. announced positive efficacy, safety and tolerability results from its 72-week SELECT-2 Phase 2b dose-finding Phase 2b trial of Locteron®, the Company's lead product candidate for the treatment of hepatitis C. For each of the three Locteron doses tested in SELECT-2, the percentage of patients who maintained undetectable levels of virus at week 60 of the trial, 12 weeks after completion of 48 weeks of treatment (SVR12), were comparable with or exceeded the response rate for the PEG-Intron® control. As a result of its controlled-release mechanism, Locteron was dosed half as frequently as PEG-Intron. PEG-Intron is one of two currently marketed pegylated interferon products for the treatment of hepatitis C, a market that currently exceeds $2.5 billion in worldwide sales.
Additional results from SELECT-2 demonstrated the substantial tolerability advantages of Locteron. Patients treated with each of the three Locteron doses in SELECT-2 reported a statistically significant reduction in flu-like adverse events (p < 0.001) compared to the PEG-Intron group. Accordingly, Locteron patients in all three dose groups used less concomitant medications (analgesics and antipyretics) than the PEG-Intron patients during the study period. Lastly, patients receiving the two lower doses of Locteron experienced lower rates of depression and discontinuations due to adverse events than patients receiving PEG-Intron.
Response rates and tolerability results for SELECT-2 are outlined in the table below:
"The strong viral response of Locteron achieved with once-every-two-week dosing is an improvement over current interferons, and I am impressed by the consistency of the flu-like effect across trials and different reporting methodologies," said Nezam Afdhal, M.D., Chief of Hepatology at Beth Deaconess Medical Center, Harvard Medical School. "The reduction in symptoms of depression is quite promising and needs to be followed up in additional clinical evaluation. The Locteron safety and tolerability results are clearly important as recent clinical results demonstrate that interferon is likely to remain a core component of future treatment regimens that incorporate the new direct-acting anti-virals, highlighting the need for a more tolerable interferon to reduce the side-effect burden on patients from these multi-drug combinations and maximize their adherence to treatment."
SELECT-2 Depression Results
In SELECT-2, depression was measured in both patient-reported and clinic-reported methods and showed an advantage for Locteron for the dose groups encompassing the expected commercial dose range, the 320 and 480 µg doses. Throughout the 48 weeks of treatment in SELECT-2, patients self-reported their status using the Beck's Depression Inventory (BDI), one of the most widely used instruments for measuring the severity of depression. 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.
In SELECT-2, depression was measured in both patient-reported and clinic-reported methods and showed an advantage for Locteron for the dose groups encompassing the expected commercial dose range, the 320 and 480 µg doses. Throughout the 48 weeks of treatment in SELECT-2, patients self-reported their status using the Beck's Depression Inventory (BDI), one of the most widely used instruments for measuring the severity of depression. 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.
These findings from SELECT-2 are of particular importance as a survey of hepatitis C patients published in the Journal of Viral Hepatitis in 2010, showed that depression and flu-like symptoms were cited as the two most important adverse events impacting patient adherence to treatment.
AASLD Presentation
Biolex also announced today that new tolerability data from two Phase 2b trials of Locteron have been accepted for a late-breaker presentation on November 1, 2010 at the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston. These latest tolerability results include daily patient self-reporting of flu-like adverse events using an electronic patient reported outcome system (ePRO).
Biolex also announced today that new tolerability data from two Phase 2b trials of Locteron have been accepted for a late-breaker presentation on November 1, 2010 at the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston. These latest tolerability results include daily patient self-reporting of flu-like adverse events using an electronic patient reported outcome system (ePRO).
"We believe that the efficacy, safety and tolerability results from SELECT-2 support the profile of Locteron as the most combinable interferon for use with direct-acting anti-viral drugs in emerging combination regimens," said Mr. Jan Turek, Biolex's President and Chief Executive Officer. "We are pleased that the ePRO results, the newest data supporting the tolerability advantages of Locteron, have been accepted for presentation at the AASLD conference."
Locteron is an investigational therapeutic candidate and has not been approved for sale by the United States Food and Drug Administration or by any international regulatory agency.
About SELECT-2 Study
Biolex's SELECT-2 Phase 2b trial was designed to identify one or more doses of Locteron that demonstrated viral kinetics and response rates comparable to the PEG-Intron® control while also achieving at least a 50% reduction in flu-like adverse events. SELECT-2 is being conducted in the United States and Europe in 116 treatment-naïve, genotype-1, chronic hepatitis C patients. Patients were randomized into one of four dosing cohorts, the 320, 480 or 640 µg dose of Locteron (administered once every two weeks) or a control arm consisting of PEG-Intron (1.5 µg/kg, administered every week), with all patients receiving weight-based ribavirin. Patients were treated for 48 weeks and are being followed for an additional 24 weeks to determine the sustained virologic response (SVR) rate. All patients in the trial have reached at least the 60-week time point of the study, or 12 weeks of follow-up after completion of the scheduled 48 weeks treatment.
Biolex's SELECT-2 Phase 2b trial was designed to identify one or more doses of Locteron that demonstrated viral kinetics and response rates comparable to the PEG-Intron® control while also achieving at least a 50% reduction in flu-like adverse events. SELECT-2 is being conducted in the United States and Europe in 116 treatment-naïve, genotype-1, chronic hepatitis C patients. Patients were randomized into one of four dosing cohorts, the 320, 480 or 640 µg dose of Locteron (administered once every two weeks) or a control arm consisting of PEG-Intron (1.5 µg/kg, administered every week), with all patients receiving weight-based ribavirin. Patients were treated for 48 weeks and are being followed for an additional 24 weeks to determine the sustained virologic response (SVR) rate. All patients in the trial have reached at least the 60-week time point of the study, or 12 weeks of follow-up after completion of the scheduled 48 weeks treatment.
In SELECT-2, all adverse events were recorded during weekly clinic visits by the clinical site personnel. Flu-like adverse events were predefined to include arthralgia, chills, fever, headache, and myalgia. Under the statistical analysis plan for the trial, the reductions in flu-like adverse events were tested after four and 12 weeks of treatment and were statistically significant for all three Locteron doses (p < 0.001 at 12 weeks for each of the 320, 480 or 640 µg doses of Locteron). In addition to the weekly clinic reporting, flu-like adverse events were self reported daily by patients through an electronic patient reported outcome system (ePRO). The ePRO results will be reported at the upcoming AASLD meeting as detailed above.
Locteron Overview
Locteron, controlled-release interferon alpha 2b, is designed to offer key advantages compared to currently approved products, including reduced flu-like symptoms and rates of depression, and cutting in half the number of injections required. In contrast to Locteron, the currently approved products, Pegasys® and PEG-Intron, are immediate-release products that lack a controlled-release mechanism. The two-drug combination of interferon alpha and ribavirin serves as the current standard of care for the treatment of hepatitis C. The launch of the first direct-acting anti-viral (DAA) product, projected for 2011, will transform treatment of genotype-1 patients to a triple-drug therapy (interferon plus ribavirin plus DAA) and substantially raise cure rates. Other recent triple or quad drug combinations (including interferon plus ribavirin plus two DAA agents) have shown promise in early clinical testing, further solidifying the continued role of interferon in the treatment of hepatitis C. It is estimated that worldwide sales of interferon products for the treatment of hepatitis C will approach $6 billion by 2016.
Locteron, controlled-release interferon alpha 2b, is designed to offer key advantages compared to currently approved products, including reduced flu-like symptoms and rates of depression, and cutting in half the number of injections required. In contrast to Locteron, the currently approved products, Pegasys® and PEG-Intron, are immediate-release products that lack a controlled-release mechanism. The two-drug combination of interferon alpha and ribavirin serves as the current standard of care for the treatment of hepatitis C. The launch of the first direct-acting anti-viral (DAA) product, projected for 2011, will transform treatment of genotype-1 patients to a triple-drug therapy (interferon plus ribavirin plus DAA) and substantially raise cure rates. Other recent triple or quad drug combinations (including interferon plus ribavirin plus two DAA agents) have shown promise in early clinical testing, further solidifying the continued role of interferon in the treatment of hepatitis C. It is estimated that worldwide sales of interferon products for the treatment of hepatitis C will approach $6 billion by 2016.
Locteron incorporates an advanced controlled-release drug delivery technology that allows dosing once every two weeks, more convenient than Pegasys and PEG-Intron, each of which require dosing every week. More importantly, Locteron's controlled-release mechanism results in the gradual release of interferon alpha 2b to patients over the duration of two weeks and avoids the early peak plasma levels of the active interferon that characterize the pegylated interferons. This controlled-release mechanism is designed to reduce the frequency and severity of flu-like symptoms and depression commonly experienced by patients treated with pegylated interferons.
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