BTG Regulatory News (BTG)

BTG Announces Positive Results from Second US Pivotal Phase III Trial of Varisolve®

Study meets all primary, secondary and tertiary endpoints with a high degree of statistical significance

Data from study VV017 also reported

On track to submit US NDA by end of 2012

London, UK, 23 April 2012: BTG plc (LSE: BGC), the specialist healthcare company, today announces the successful outcome of VANISH-1, the second and final US pivotal Phase III trial of Varisolve® (polidocanol endovenous microfoam (PEM)) as a potential treatment for patients with saphenofemoral junction incompetence and symptomatic and/or visible varicose veins. All end points were met with all active PEM concentrations with a high degree of statistical significance.

Patients treated with PEM (0.5%, 1.0% or 2.0% dose concentrations) demonstrated a statistically significant improvement in symptoms, the primary endpoint, compared with patients who received placebo (p < 0.0001). The co-secondary endpoints of improvement in appearance in PEM-treated patients (0.5%, 1.0% or 2.0% dose concentrations) compared with patients who received placebo, as measured by both a patient-reported outcome and by a blinded independent panel review of photographs, were also met (p < 0.0001 and p < 0.0001, respectively).

The three tertiary endpoints, response to treatment as determined by duplex ultrasound, change in the Venous Clinical Severity Score and Quality of Life as measured by the modified VEINES-QOL/Sym questionnaire, were all statistically significantly better for patients treated with PEM (0.5%, 1.0% or 2.0% dose concentrations) compared to patients who received placebo (all at p < 0.0001).

These results confirm the positive results announced on 30 January 2012 from VANISH-2, the first US pivotal Phase III trial. Based on the successful outcome of these two pivotal Phase III trials, BTG intends to submit a New Drug Application in the US, seeking approval of PEM as a comprehensive treatment for symptoms and appearance of varicose veins by the end of 2012.

VANISH-1 investigator Ted King, MD, National Medical Director of Vein Clinics of America, said: "VANISH-1 and VANISH-2 are extremely rigorous trials that have both shown clear benefits of treatment with PEM in patients with symptomatic varicose veins, as assessed by the patients and their treating physicians and in a randomized, controlled manner. With these strong efficacy results and the demonstrated safety profile, PEM should become an important new treatment option."

A smaller study (VV017) evaluated patients treated first with heat ablation of the great saphenous vein (GSV) followed by treatment with PEM (0.5% and 1.0% dose concentrations) or placebo for the remaining visible varicosities. In this study, appearance was measured by co-primary endpoints, a blinded independent panel review of photographs and a patient-reported measure of appearance. Relative to baseline, all PEM treatment groups demonstrated a greater improvement in appearance than placebo by both measures. Statistical significance was achieved for the blinded independent panel review of photographs (p = 0.001) but not for the patient-reported measure of appearance, hence the primary objective of the study was not achieved.

The safety profile of PEM in VANISH-1 and VV017 was consistent with previous clinical studies and, as previously reported, there were no serious or unexpected adverse events associated with the use of PEM across the whole Phase III programme, in which 590 patients received PEM and there were 984 PEM treatments in total. There were no cerebrovascular events or pulmonary emboli reported in any study.

Louise Makin, BTG's CEO, commented: "Based on the successful outcome of our two pivotal trials, VANISH-1 and VANISH-2, which met all their endpoints with a high degree of statistical significance, we are on track to submit our US regulatory application by the end of 2012. We will be seeking the approval of PEM as a comprehensive treatment to improve both the symptoms and appearance of varicose veins. This is the first time patient benefit has been shown using patient-reported outcome measures in pivotal Phase III trials in patients with varicose veins."

VANISH-1 included 284 patients who were randomised to receive treatment with one of four dose concentrations (0.125%, 0.5%, 1.0% or 2.0%) of PEM (n = 227) or "vehicle", effectively a placebo comparator (n = 57). The primary endpoint of the study was an improvement in symptoms recorded by patients using a validated patient-reported outcomes instrument, VVSymQ™. Patients scored a variety of symptoms such as swelling and aching using a daily electronic diary for 10 days prior to treatment (baseline) and for an additional 10 days prior to the primary endpoint at eight weeks following treatment. The secondary endpoint was the improvement in appearance and was measured both by patients, who used another validated patient-reported outcome instrument, PA-V3 and by an independent panel review of photographs in a blinded setting using a validated clinician-reported instrument, IPR-V3.

VV017 included 118 patients who were randomised to receive heat ablation treatment of the great saphenous vein followed by one of two dose concentrations (0.5% or 1.0%) of PEM (n = 80) or "vehicle", effectively a placebo comparator (n = 38) to treat the remaining veins. The primary endpoint was the improvement in appearance of the visible varicosities and was measured both by patients, using PA-V3, and by an independent panel review of photographs, using IPR-V3.

PEM is generated by a unique patent-protected drug/device combination. It is a highly uniform CO2/O2 polidocanol endovenous microfoam, engineered to improve safety and efficacy in the treatment of varicose veins. PEM is injected directly into the incompetent vein under ultrasound guidance, where it first displaces blood thereby enabling the polidocanol to chemically ablate the inner lining of the vein wall, causing the vein to close. A compression bandage is applied to the treated leg for a period of approximately two weeks. If approved, PEM would be the first non-surgical, comprehensive treatment for varicose veins.

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About BTG

BTG is an international specialist healthcare company that is developing and commercialising products targeting critical care, cancer and other disorders. The Group is seeking to acquire new products to develop and market to specialist physicians, and is building a sustainable business financed by revenues from sales of its own marketed products and from royalties and milestone payments on partnered products. For further information about BTG please visit our website at www.btgplc.com.