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Data From Pivotal Phase III Trials Of Varisolve® PEM For Patients With Saphenofemoral Junction Incompetence And Varicose Veins

BTG plc (LSE: BTG), the specialist healthcare company, have announced that full data from VANISH-1 and VANISH-2, the two US pivotal Phase III trials of polidocanol endovenous microfoam (), were presented at the 26th Annual Congress of the American College of Phlebology in Hollywood, Florida, USA on 16 November 2012.

PEM is in development for patients with saphenofemoral junction incompetence and symptomatic and/or visible . VANISH-1 and VANISH-2 had the same endpoints and all primary (improvement in symptoms), secondary (improvement in appearance) and tertiary (duplex response, venous clinical severity score (VCSS) and VEINES-QOL questionnaire) endpoints were met with all therapeutic PEM concentrations compared to placebo with a high degree of statistical significance (p < 0.0001).

In the first presentation, Kenneth Todd, MD, a Principal Investigator for VANISH-2 and an American College of Phlebology Committee Member from the South East Vein and Laser Center, described the results of VANISH-2 in his talk entitled: ‘A Phase III study to investigate the efficacy and safety of PEM on the symptoms of varicose veins’.

Dr. Todd noted that 80% of patients treated with PEM 0.5% or 1.0% dose concentrations reported a much or moderate improvement of symptoms, as measured with the novel VVSymQ™ patient reported outcome (PRO) instrument compared to 20% in the placebo arm. In addition, 85% of patients demonstrated elimination of saphenofemoral junction reflux and/or occlusion of the great saphenous vein and all incompetent veins, as measured by duplex ultrasound compared with 2% in the placebo arm. Dr. Todd concluded that PEM treatment of the great saphenous vein (GSV) system has demonstrated efficacy in improving symptoms in patients with varicose veins.

Patients treated in this study were representative of a typical varicose veins population, with an age range of 21 to 73 and baseline GSV diameter range of 3 mm to 19 mm. In this trial, where patients could have received up to two blinded treatments to treat the entire GSV system and visible varicosities, patients treated with PEM 1.0% received an average of 1.4 blinded treatments.

Side effects were mostly mild or moderate. There were no serious adverse events or cerebrovascular events attributable to PEM treatment. No pulmonary emboli were reported. The most common adverse events were expected and included retained coagulum, pain and superficial thrombophlebitis.

Out of 230 PEM-treated patients, 6 experienced proximal and 7 distal deep vein thrombosis; other venous thrombi occurred as extensions from the GSV into the common femoral vein (9), and isolated calf vein thrombi (2). All thrombi were small and most (77%) were asymptomatic, and all resolved or stabilized in a median time of 29 days; half of the cases were treated with anticoagulation per the discretion of the physician.

In the second presentation, Ted King, MD, one of the Principal Investigators for VANISH-1 and the National Medical Director of the Vein Clinics of America, described the results of VANISH-1 in a talk entitled: ‘Phase III study of PEM on the appearance of varicose veins’.

Dr. King focused on the improvement in appearance as measured by the patient self-assessment PRO tool, PA-V3, and by an independent physician review of before and after photos in a blinded setting using a clinical reported instrument, IPR-V3. 64% of patients treated with active PEM dose concentrations (PEM 0.5%, 1.0% and 2.0%) reported a much or moderately improved appearance eight weeks after treatment compared to 4% in the placebo arm. 79% of treatments resulted in a much or moderately improved appearance as measured by physicians using the IPR-V3 tool compared to 9% in the placebo arm.

Dr. King concluded that PEM demonstrated efficacy in achieving a clinically meaningful improvement in the appearance of legs in patients with chronic venous insufficiency and superficial varicose veins in a single treatment session from both a patient perspective and independent physician review. He noted that a single treatment demonstrates increasing efficacy with increasing concentration and that efficacy was similar between PEM 1% and 2%. Patients treated in this study were representative of a typical varicose veins population. Only one blinded treatment per patient was permitted in the VANISH-1 trial.

The safety profile was consistent with that seen in VANISH-2: adverse events were mostly mild or moderate and there was a modest increase in side effects as dose concentration increased. The most common adverse events were pain, superficial thrombophlebitis, injection site haematoma and limb discomfort. Out of 275 PEM-treated patients 5 experienced proximal and 4 distal deep vein thrombosis; other venous thrombi occurred as extensions from the GSV into the common femoral vein (15) and isolated calf vein thrombi (3). All venous thrombi resolved or stabilized; there were no reported pulmonary emboli or recurrent thrombi.

Dr. Todd commented: “Current treatments for patients with medically-important, symptomatic varicose veins are time-consuming for both patients and physicians and do not offer a comprehensive treatment. The publication of the full results for VANISH-1 and VANISH-2 confirm the top-line results already reported and demonstrate that PEM, if approved, could offer an effective, comprehensive treatment option for patients with symptomatic varicose veins.”

PEM is a patent-protected experimental drug/device combination product which produces an engineered polidocanol endovenous microfoam manufactured in accordance with GMP standards. PEM is delivered from a canister through a syringe into the incompetent vein under ultrasound guidance. PEM first displaces blood and then the polidocanol chemically ablates the inner lining of the vein wall, causing the vein to close. A compression bandage is applied to the leg for a period of approximately two weeks.