ORLANDO – One number keeps coming up with the new autologous fibroblast biologic product that enhances a patient’s nasolabial wrinkles: three.
"There are a lot of threes: three biopsies 3 mm in size, a 3 month’s wait, and three treatment sessions," Dr. Robert Weiss said at the annual meeting of the Florida Society of Dermatology Surgeons.
Dr. Robert Weiss
The Food and Drug Administration cleared the marketing of Fibrocell Science’s azficel-T (LaVív) in June 2011, and the product is now reaching the market. "It’s very exciting to be right at the launch of this," said Dr .Weiss, a dermatologist in private practice in Hunt Valley, Md., and with the dermatology department at Johns Hopkins University, Baltimore. "I’ve been working on this for close to a decade, so it was a personal triumph to see this finally cleared by the FDA."
The FDA based its clearance on two identically designed, multicenter, double-blind, vehicle-controlled studies. A total of 421 patients with moderate to severe nasolabial fold wrinkles were assessed, with 210 being randomized to azficel-T and 211 to vehicle injections. The average age was 55 years, and 90% were women.
A 2-point improvement in the appearance of the nasolabial fold wrinkles was the primary outcome. Physicians at the study sites who were not injectors blindly rated results.
At the 6-month follow-up, doctors observed the 2-point improvement in 33% of the azficel-T group, compared with 7% of controls in the first study. In the second study, 19% of the azficel-T group had at least a 2-point improvement, compared with 7% of controls. These differences were on the borderline of statistical significance, Dr. Weiss said.
"The FDA was convinced that this was effective. We were certainly very convinced by what we observed with the patients," Dr. Weiss said.
Patient reported outcomes were more statistically significant, with 57% reporting a 2-point improvement, compared with 30% in the vehicle group in an intent-to-treat analysis of the first study. In the second study, 45% of the treated patients reported this outcome, compared with 18% of the vehicle group.
The most common adverse effects were injection site reactions lasting approximately 2 hours, Dr. Weiss said. These events included erythema, bruising, and swelling. Facial or eyelid edema, hypersensitivity or decreased skin sensation at the injection site, and postprocedural discomfort were among the adverse events reported by 1% of patients or fewer.
"One of the first questions patients ask me is: ‘How are you going to make sure I’m getting my own cells?’ " Dr. Weiss explained there are strict controls. Each patient is assigned a lot number. Vials for injection are labeled with each patient’s initials, date of birth, and a unique identification number. "All the critical steps are verified twice."
The treatment protocol involves extraction, purification, culturing, and injection. Dr. Weiss said he injects 1 cc to 2 cc of lidocaine in the postauricular area before taking the biopsies. The tissue is sent to Fibrocell for purification and culturing of the fibroblasts.
After 3 months, a vial containing 15 million to 20 million fibroblasts is shipped back to arrive just prior to the patient appointment. "Advise your patients that advance notice of at least 2 business days is required to reschedule treatment. By the FDA guidelines, you cannot inject the cells the next day because the viability count goes down." Treatment at 3- to 6-week intervals is recommended.
Because the product is a biologic, the FDA requires physician certification prior to use of azficel-T. "If you are interested in offering this to your patients, the company will train your staff. There are webinars," Dr. Weiss said. Staff training reinforces proper packing, handling, and shipping.
The product has to be handled gingerly and injected superficially in the papillary dermis, he said. "This is for superficial rhytids; this is not a deep volume filler." The needle will be visible under the skin if you are injecting in the right plane.
Resuspend the cells by inverting the vial slowly a few times. Be careful putting the vial on the tray because it can fall over. Apply light pressure to the plunger and inject slowly along the wrinkle line.
Instruct the patient not to wash the site for 24 hours and not to scrub, rub, massage, or apply any pressure for 72 hours. An NSAID can be taken for pain.
Also, instruct patients to call if they experience any adverse reactions. Fibrocell plans to launch a patient registry in July 2012 that will track hypersensitivity reactions.
Dr. Weiss participated in one of the clinical trials as early as 2003. "What we’ve noted on long-term follow-up is that patients maintain this improvement, often for many, many years, which is interesting."