Foam. You’ve heard much, probably even seen its benefits in action. Now the FDA has approved Varithena™ (polidocanol injectable foam), and this year it will finally be a reality. But what do you really know about the stuff?
BTG, the parent company of Varithena™, published the results of the VANISH-2 study in which patients with symptomatic and visible varicose veins caused by saphenofemoral junction (SFJ) incompetence were treated with Varithena™, formerly known as Varisolve, or polidocanol endovenous microfoam (PEM). This formulation has been in development for over a decade, and BTG has tried for many years to get the product licensed.
Sclerosants, as we know, are successful because of their damaging effects to the delicate lining of the vein, causing it to clot, seal and close itself off. The degree of the damage to the vein lining caused by the sclerosant is dependent upon the contact time of the chemical, along with the concentration of the drug. Because many sclerosants are detergents by nature, they form bubbles easily. Foaming the sclerosant enables it to push the blood out of larger veins and allows for longer contact time within the vein wall, enhancing the effect.
With the approval of Varithena™, BTG stands to gain quite a bit, claiming it to be one of the biggest developments in the vein procedure market in 40 years. Still, many say that while it is a significant accomplishment, it does have to compete in a market with many proven and highly effective, minimally invasive modalities available as alternatives. Nevertheless, BTG is ready for the fight.
Data from the published study indicate that Varithena™ “provides a clinically meaningful benefit in treating symptoms and appearance in patients with varicose veins caused by SFJ reflux.” BTG reported that the study achieved primary, secondary and tertiary efficacy endpoints in patients with vein diameters ranging from 3.1 to 19.4 mm.
Previously, the biggest concerns around the product came from reports of micro-emboli causing mini-strokes and chest pain after use. BTG, therefore, conducted extensive clinical studies to show that the risks of these side effects were minimal enough to warrant FDA approval.
Louise Makin, CEO at BTG, said: “We are delighted to receive US approval for Varithena™, which we believe sets a new standard for the treatment of both the symptoms and appearance of varicose veins. We look forward to the commercial US launch in the second quarter of 2014, and to continuing to advance our plans to expand use into other geographies and into non-symptomatic veins.”
What is important to know about the safety of Varithena™?
In clinical trials, the most common adverse events (occurring in ≥3% of patients treated with Varithena™) were pain/discomfort in extremity, infusion site thrombosis (retained coagulum), injection site hematoma or pain, thrombophlebitis superficial, and extravasation.1
The safety profile of Varithena was evaluated in 1,333 patients in 12 clinical trials, including three placebocontrolled, randomized trials.1
- No anaphylaxis or life-threatening hypersensitivity reactions were reported by any of the 1,333 patients treated with Varithena™.2
- No clinically important neurologic or visual adverse events suggestive of gas embolism were seen in any of the 1,333 patients treated with Varithena™.1 In the three placebo-controlled trials, the incidence of neurologic and visual adverse events within 1 day was 2.7% in patients treated with any dose of Varithena™ (n=437) and 4.0% in placebo-treated patients (n=151).1
What You May Not Know…
In an effort to better understand Varithena™, VEIN spoke with Ted King, MD, FACPh, a primary investigator of the drug, who currently serves as the Vice President of Medical Affairs of Vein Clinics of America and is also a National Director of the American College of Phlebology. We wanted to know the story behind the story…
VM: How did you come to be involved in the research of Varithena™?
TK: When I became a phlebologist more than 16 years ago, my training was heavily weighted toward ultrasound-guided sclerotherapy. Just a short time later, I was introduced to foam and saw the difference in efficacy that use of a foamed sclerosant makes. I had the opportunity to meet David Wright [Vice President of Medical Affairs at BTG] at a meeting in Brighton, England in 2004. There, we talked and I learned some details about Varisolve (now Varithena™). A more effective and safer foam? I was hooked.
VM: What was the most surprising data you discovered with this research process?
TK: One of the most amazing things to me was that the FDA wasn’t interested in the typical surrogate marker of treatment success: vein closure. They wanted to know that patients received benefit, both visually and symptomatically, from their treatment. This was assessed through use of the VVSymQ®, the first vein disease specific PROM (patient reported outcome measure) that has been created under FDA guidelines for PROMs. Patient improvement in appearance (as assessed by the patients and by a panel of experts examining photographs) and in their vein related symptoms (assessed by the VVSymQ®) was statistically significantly higher with Varithena™ than placebo. At the same time, the treated vein, as seen on ultrasound, closed more than 80% of the time with only one treatment–even with GSVs as large as 25.9 mm in diameter! As for its safety, what is surprising is what didn’t occur. No major neurologic events occurred with more than 1300 patients treated in clinical studies. No anaphylactic reactions occurred and there were no pulmonary emboli. The most typical side effects were what you would expect to see: bruising, discomfort, retained coagulum, and the like. And it is versatile. Varithena™ has FDA approval for the treatment of the GSV, saphenous accessories, and varicose tributaries above and below the knee.
VM: Now that Varithena™ has been researched and approved, what do you feel the benefits are versus physician-compounded foam?
TK: There are several. With the approved 1% dose concentration, the benefits are:
- Proven safety with high patient tolerance
- Proven efficacy with only one treatment
- FDA approval for a broad range of refluxing veins
- Product consistency–low nitrogen content with consistently uniform density, stability, and range of bubble size (median diameter of 500 μm)
- Varithena™ is the only standardized, low-nitrogen foam. You know what you are putting into your patient.
VM: How often do you think you will use Varithena™ in your practice in the treatment of varicose veins?
TK: When it is available some time later this year, it will be the only comprehensive therapy for the widest range of varicose veins—incompetent great saphenous veins, accessory saphenous veins and visible varicose tributaries GSV system above and below the knee. There are no special energy sources or other expensive equipment to buy and Varithena™ doesn’t require use of tumescence. I see the potential for me to use it a lot.
Varithena Study Specifics
Patients treated with Varithena™ demonstrated a statistically significant improvement in symptoms at week 8, the study primary endpoint as measured by the VVSymQ® score, compared with patients who received placebo (P<0.0001). The VVSymQ® score is a patient-reported outcome measure of varicose vein symptom burden. The study’s co-secondary endpoint, improvement of appearance as measured by both a patient-reported outcome (PA-V3) and by a blinded independent panel review of photographs (IPR-V3), was also met. Patients treated with Varithena™ achieved a statistically significant improvement in appearance in both the PA-V3 and IPR-V3 scores compared with patients who received placebo (P<0.0001 for both).
At week eight, eight out of 10 patients in the pooled Varithena™ group (composed of Varithena™ 0.5% and Varithena™ 1.0%) reported clinically meaningful improvements in symptoms compared to 20 percent in the placebo group. Additionally, treatment with Varithena™ was superior to placebo in improving symptoms when either a duration or intensity scale was used to measure patients’ symptoms. The improvement in symptoms was supported by statistically significant improvements in the Venous Clinical Severity Score (VCSS) and Venous Insufficiency Epidemiological and Economic Study−Quality of Life (VEINES-QOL) score compared to placebo. Elimination of SFJ reflux and/or complete occlusion of the target vein(s) at week eight, a tertiary endpoint, was achieved by 85 percent of patients in the pooled Varithena™ group (P=.0002, compared with the control group Varithena™ 0.125%). This endpoint was achieved in 83 percent and 86 percent of patients receiving Varithena™ 0.5% and Varithena™ 1.0%, respectively. There were no serious or unexpected adverse events associated with the use of Varithena™. No pulmonary emboli were detected and no clinically important neurologic or visual adverse events were reported. Of the 230 Varithena™-treated patients (including open-label patients), 60 percent had an adverse event compared with 39 percent of placebo; 95 percent were mild or moderate. The most common adverse events in patients treated with Varithena™ were retained coagulum, leg pain and superficial thrombophlebitis; most were related to treatment and resolved without sequelae.