OctoPlus announces promising results for Locteron Phase IIa clinical studyAMSTERDAM, July 26, 2007-OctoPlus N.V. ("OctoPlus" or the "Company") (Euronext: OCTO), the drug delivery and development company, announces today positive initial results of the ongoing SELECT-1 Phase IIa study with its lead product Locteron(TM) , a controlled release interferon alfa for the treatment of chronic hepatitis C (HCV). In the 12-week Phase IIa study, the combination of the highest dose of Locteron evaluated until now, and the antiviral drug ribavirin, achieved an early virologic response (EVR) in 100% of the hepatitis C patients treated. The study reported an overall strong antiviral response at twelve weeks and an adverse event profile that shows substantial tolerability improvement compared to other interferons, either on the market or in development. OctoPlus is co-developing Locteron with its partner Biolex Therapeutics.
These initial results are from the first three cohorts (160, 320 and 480 ug); treatment of the fourth and last cohort (640ug) is ongoing. Complete and final study results will be reported in the fourth quarter of this year.
Professor Peter Jansen, head of the AMC Liver Center at the department of Gastroenterology and Hepatology of the Academic Medical Center in Amsterdam, the Netherlands, comments:
"These results are very encouraging: Locteron´s adverse event profile shows potential to significantly improve hepatitis C therapy. The results pave the way for the commencement of the Phase IIb study, in which I am excited to be involved."
Design of the Phase IIa study
The SELECT-1 (Safety and Efficacy of Locteron: European Clinical Trial 1) Phase IIa study is a European multi-center, randomized, open-label trial designed to evaluate Locteron in combination with the anti-viral drug ribavirin in previously untreated chronic hepatitis C patients. A total of 32 patients in 4 dose cohorts have been enrolled in the study. The study assesses safety and tolerability and explores viral response of a 12-week treatment with Locteron, administered once every two weeks in subcutaneous doses of 160, 320, 480 and 640 ug, and combined with oral ribavirin treatment. Dosing of the first three eight-patient cohorts commenced in January 2007. Based on a favorable safety review of the results from the first three cohorts, dosing of patients in the 640 ug cohort commenced in May 2007.
Antiviral response in doses 160, 320 and 480 ug
At the conclusion of the study, 12 weeks of treatment, the results for the 160, 320 and 480 ug cohorts were as follows:
- A dose response was observed in the study, with patients treated with the 320 and 480 ug doses of Locteron demonstrating a greater reduction in hepatitis C virus than the patients treated with the 160 ug dose at all measurement times. Average viral reduction after 12 weeks of treatment for the 320 and 480 ug doses was 4.5 and 4.2 logs, respectively, compared to 1.8 logs in the lowest dose of 160 ug.
- After 12 weeks of treatment, 63% (5/8) of the patients had undetectable levels of hepatitis C virus, measured by plasma RNA < 28 IU/ml, in both the 320 and 480 ug dose cohorts, compared to 13% (1/8) of the patients in the lowest-dose group of 160 ug.
- The percentage of patients who achieved early virologic response (EVR), defined as at least a two-log reduction in hepatitis C virus after 12 weeks of treatment, was 88% (7/8) and 100% (8/8) in the 320 and 480 ug dose Locteron cohorts, respectively, compared to 38% (3/8) of the patients in the lowest-dose group of 160 ug. Achievement of EVR has been broadly established to be a pre-requisite for long-term response.
Safety and tolerability in doses 160, 320 and 480 ug
The following Locteron side effect and patient tolerability results were observed during the 12 weeks of treatment for the 160, 320 and 480 µg cohorts:
- Locteron was safe and well tolerated.
- There were no serious adverse events.
- The vast majority (over 90%) of the adverse events that were experienced were rated as mild.
- Dose reductions were limited to one patient each in the 320 and 480 ug cohorts with none in the 160 ug cohort.
- No patients discontinued treatment.
Side effects were confined to the regular flu-like symptoms and other side effects that are associated with interferon treatment. All adverse events, including flu-like symptoms, were less frequent and less severe than the side effects reported for other interferons. For example, only one patient in the SELECT-1 study receiving Locteron experienced an adverse event rated as severe, a substantial improvement over reported results for Pegasys® and Albuferon(TM) as illustrated below.
Another objective point of comparison for evaluating the tolerability of Locteron and other interferon products across clinical studies is fever, a marker for the family of adverse events characterized as flu-like symptoms. Fever occurred in only one (4%) of the Locteron patients in SELECT-1, notably lower than other interferon products, as illustrated below.
Furthermore, the rates of other side effects reported for pegylated interferons and Albuferon, such as chills, nausea, diarrhea and dizziness, were also markedly lower in patients treated with Locteron in SELECT-1. All other side effects were predominantly mild and were comparable with other interferon products.
Joost Holthuis, CEO of OctoPlus, says: "We are very excited to be able to present these promising results, which show the potential of Locteron to be a convenient and effective hepatitis C therapy with less side effects than its competitor products. We look forward to starting the next development phase, a Phase IIb study with Locteron, in 2008".
Biolex and OctoPlus plan to commence SELECT-2, a Phase IIb study of Locteron in 2008 after assessment of the final results from the SELECT-1 Phase IIa study in the fourth quarter of 2007. The 12-week results of the Phase IIb trial will be used as the basis for dose selection for the commencement of the Phase III development program.
OctoPlus will hold a conference call today at 10 AM CET. If you would like to participate in the conference call, please request the details from Ms. Rianne Roukema at OctoPlus, telephone number +31 (71) 524 1071. During the conference call Joost Holthuis, CEO of OctoPlus, will comment on the results of the Phase IIa study and will be available to answer questions.
For further information, please contact:
Rianne Roukema, Corporate Communications: +31 (71) 524 1071
Notes to editors:
Locteron is designed to be a best-in-class therapeutic for patients with chronic hepatitis C, with the potential to induce less side effects, improve patient compliance and provide a more convenient once every two week dosing schedule compared with current therapies. The need for improved patient tolerability will become even greater with the emergence of new oral anti-viral products. These emerging antiviral products are associated with additional side effects, further adding to the opportunity for Locteron to be the interferon of choice for future combination therapy as a result of its potential for improved tolerability.
Locteron combines OctoPlus´ proprietary PolyActive(TM) drug delivery technology with BLX-883, a recombinant alfa interferon produced by OctoPlus´ co-development partner Biolex Therapeutics in its patented LEX System(SM). Locteron is produced in OctoPlus´ cGMP manufacturing facilities in Leiden, the Netherlands.
About hepatitis C
More than four million people in the United States, and more than 200 million people worldwide, are currently infected with hepatitis C. The standard treatment for patients with chronic hepatitis C is pegylated interferon alfa administered in combination with the anti-viral drug ribavirin. The currently available pegylated alfa interferon products require administration once per week for up to 48 weeks and are associated with substantial side effects, particularly during the period following each administration. Independent market research predicts that modified interferons will continue to be a key component of combination therapy for hepatitis C patients and is expected to be complementary with new agents under development. These sources estimate that total interferon sales for the treatment of hepatitis C will exceed $5 billion by 2014.
OctoPlus N.V. is a product-oriented biopharmaceutical company committed to the creation of improved pharmaceutical products that are based on OctoPlus´ proprietary drug delivery technologies and have fewer side effects, improved patient convenience and a better efficacy/safety balance than existing therapies. Rather than seeking to discover novel drug candidates through early stage research activities, OctoPlus focuses on the development of long-acting, controlled release versions of known protein therapeutics, other drugs, and vaccines. Our pipeline consists of 5 products in preclinical and clinical development. Our lead product is Locteron, a sustained-release formulation of interferon alfa for the treatment of chronic hepatitis C, which we are co-developing with Biolex Therapeutics. Locteron is in Phase IIa clinical development. Furthermore, our pipeline comprises a product for the treatment of chronic middle ear infection also in Phase II development, a sustained-release formulation of growth hormone in Phase I and two preclinical single-shot vaccines.
In addition, OctoPlus is a leading provider of advanced drug formulation and clinical scale manufacturing services to the pharmaceutical and biotechnology industry, with a focus on difficult to formulate active pharmaceutical ingredients in injectable formulations. The earnings and expertise that we derive from rendering formulation and manufacturing services help to support our own drug development programs.
This document may contain certain forward-looking statements relating to the business, financial performance and results of OctoPlus N.V. and the industry in which it operates. These statements are based on OctoPlus N.V.´s current plans, estimates and projections, as well as its expectations of external conditions and events. In particular the words "expect", "anticipate", "predict", "estimate", "project", "plan", "may", "should", "would", "will", "intend", "believe" and similar expressions are intended to identify forward-looking statements. We caution investors that a number of important factors, and the inherent risks and uncertainties that such statements involve, could cause actual results or outcomes to differ materially from those expressed in any forward-looking statements. In the event of any inconsistency between an English version and a Dutch version of this document, the English version will prevail over the Dutch version.
Posted: July 2007