FDA Panel Backs Radiesse Approval, With Conditions

More documents

Recommendations

Info

20 Dermatologic Surgery S KIN & ALLERGY N EWS • October 2006 Two Indications Green Lighted Radiesse from page 1 in how to use the product received unanimous endorsement from the panel. Bio- Form is planning a training program and will incorporate some of the panel’s recommendations, Stephen L. Basta, president and CEO of the company, said at the meeting. Another condition recommended for the HIV-associated lipoatrophy indication was completion of the 18-month followup study being conducted by BioForm, which panelists said should include data on the texture of the implant, ease of injection, events that require further evaluation, and time needed to reinjection. The label should also state that Radiesse was studied specifically in patients with HIVrelated lipoatrophy and that use for other indications was unproved. Nasolabial Fold Indication For the nasolabial fold indication, the panel agreed that Radiesse was effective for up to 6 months, the length of the study submitted for approval. But as a condition for approval, the panel recommended that the company conduct a postapproval study specifically looking at the duration of the cosmetic effects beyond 6 months, the effect of repeated injections, and safety. Other conditions were that the company conduct a study of Radiesse in “people of color”—who tend toward hypertrophic scarring and keloid formation and were underrepresented in the study submitted to the FDA for approval of this use—and that a statement be added to the product’s label cautioning that safety and efficacy of the product in black patients was not known. In this study, there were 2 African Americans, 11 Hispanic patients, and 2 patients whose race was described as “other.” (In the lipoatrophy study, about half the patients were Fitzpatrick skin type IV-VI, which was not associated with a greater rate of adverse events; the company cited these to address the issue of safety for treating nasolabial folds. But the FDA executive summary noted that the two patient populations are not homogeneous and that the HIV-positive patients in the lipoatrophy study may have had a “diminished capacity to mount a hypersensitivity reaction.”) According to the company, the proposed label already includes a statement that the product has not been studied for use in lip augmentation and that adverse events have been reported, so the panel did not include this as a condition. The use of Radiesse for lip augmentation has not been studied, and based on reports the company has received, lips are the most common site of nodular formation associated with use of Radiesse, Mr. Basta said. Register now for this archived webcast at www.viralskindiseases.com Introduction Stephen K. Tyring, MD, PhD, MBA Professor of Dermatology Department of Dermatology University of Texas Health Science Center Houston, Tex. Human Papillomaviruses: Basic Virology to Clinical Management Stephen K. Tyring, MD, PhD, MBA Molluscum Contagiosum and Treatment Options Douglas W. Kress, MD Chief of Pediatric Dermatology Children’s Hospital of Pittsburgh Pittsburgh, Penn. Treatment of Cutaneous Warts: An Updated Inventory of Therapeutic Options Robert B. Skinner, MD Professor of Medicine Department of Dermatology University of Tennessee Health Science Center Memphis, Tenn. PROGRAM DESCRIPTION Viral skin diseases represent a major component in the busy practices of dermatologists. In this activity, the focus is on the most common cutaneous viral diseases, genital/anal warts (condylomata acuminatum) and common warts, caused by human papillomaviruses (HPV), and molluscum contagiosum, caused by Poxviruses. The manifestations of cutaneous viral infections range from simple erythematous, macular presentations to papules, vesicles, pustules, ulcers, and crusting that may represent any of a long list of possible etiologies. Clinicians must be able to accurately assess and differentiate among these manifestations and presentations, particularly now because of the emerging possibility that the causative organisms may be the etiologic agents responsible for smallpox infections or disseminated vaccinia. The poxviruses, especially, may mimic or be mimicked by vaccinia, and clinicians should know the differences in the morphology of the lesions as well as in the presentation, timing, and progression of these lesions. Advances in the understanding of the natural history and treatment of common viral skin diseases highlight the need for a continuing educational process that guides the clinician in patient management, including the latest treatment options, such as topical immune response modifier therapy. This activity will provide dermatologists with current information regarding the nature of viral skin diseases caused by HPV and poxviruses and will help clinicians remain up-to-date on patient applied and physician applied therapies in the treatment of genital warts, common warts, and molluscum contagiosum. INTENDED AUDIENCE This activity has been developed for dermatologists, primary care physicians, and other clinicians who are involved in the diagnosis and treatment of viral skin diseases. EDUCATIONAL OBJECTIVES After reading this supplement and taking the test, participants should be able to: • Summarize the current understanding of the pathogenesis of human papillomavirus (HPV) infections of the skin—as manifested by genital/anal and common warts—and the role of local immune responses in the clearing of infection. • Discuss the HPV types that are associated with external genital/anal warts and with cervical malignancies, and explain the role of diagnostic testing in the management of patients with external genital/anal warts. • Recognize the most common presentations of human papillomavirus (HPV) and poxvirus infections, as well as the atypical morphologic characteristics that must be considered in diagnosing various types of warts and molluscum contagiosum. • Describe the methods that may be used to confirm a clinical diagnosis of molluscum contagiosum, and explain when such methods should be used. • List and explain the destructive/ablative methodologies and the pharmacologic treatments that are currently available for treating genital/anal and common warts and molluscum contagiosum. • Name and describe the factors that should be considered in choosing a specific therapeutic regimen for individual patients. ACCREDITATION STATEMENT This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the Elsevier Office of Continuing Medical Education (EOCME) and Skin & Allergy News. The EOCME is accredited by the ACCME to provide continuing medical education (CME) for physicians. CME CREDIT STATEMENT The EOCME designates this educational activity for a maximum of 1 AMA PRA Category 1 Credit . Physicians should only claim credit commensurate with the extent of their participation in the activity. Financial Support: This CME activity is supported by an educational grant from Panel Members’ Concerns Like others on the panel, Dr. Michael Miller, professor and deputy chairman in the department of plastic surgery at the University of Texas M.D. Anderson Cancer Center, Houston, agreed that there was reasonable assurance that Radiesse was safe and effective for the lipoatrophy indication. The benefits for this population were “enormous,” and although the cosmetic effect of Radiesse was not permanent, its effect was “good, if not better than anything else” used for HIV-associated lipoatrophy. He cautioned, however, that Radiesse works by creating a volume-filling scar, which is acceptable only if it achieves the desired effect. Several panelists agreed with Dr. Miller, who said that the study convincingly showed efficacy and that its long history of use for various indications helped mitigate the unknowns. Dr. Michael Olding, chief of the division of plastic surgery, George Washington University, Washington, said that while he had concerns about the lack of information in histology and the length of durability, he pointed out that no significant complications were observed in the study and the quality of improvements seen in the patient photographs, in his view, “surpassed” the results of other treatments, at least photographically. The dermatologist on the panel, Dr. Amy E. Newburger of Scarsdale, N.Y., who voted against approval for both indications, expressed concern about the extensive off-label cosmetic use of Radiesse that has already occurred and is expected post approval, and about the lack of human histologic data for the product. She said the study in HIV-associated lipoatrophy was not large or rigorous enough to make her feel comfortable about effectiveness and safety, referring to reports of serious adverse reactions associated with Radiesse reported to the FDA’s adverse event reporting database, including reports resulting from unapproved use in lips. And while the study on the nasolabial folds indication was a better study than the lipoatrophy study, she said there were “too many unknowns remaining” to vote for approval for this indication. Radiesse Continued on following page
October 2006 • www.skinandallergynews.com Dermatologic Surgery 21 Continued from previous page lasts longer than hyaluronic acid fillers, so a more rigorous study is needed to achieve “any level of comfort regarding safety,” she said. Stephen Li, Ph.D., president of Medical Device Testing and Innovations, Sarasota, Fla., who also voted against approval for both indications, echoed the concern about the lack of human histologic data, pointing out that Radiesse’s migration and dissipation patterns and its reaction with other fillers in patients were unknown. The FDA usually follows the recommendations of its advisory panels, which are not binding. The safety profile of both products was comparable, with the typical injection-related side effects seen with other dermal fillers, including ecchymoses and a significant amount of erythema. Only 2 African American patients were enrolled, which was one of the main concerns raised in the FDA review, although the company reported no scarring, hyperpigmentation, or keloid formation among the 15 patients of color in the study, including the 2 African Americans. The FDA review also raised concerns that Radiesse implants could mimic a tumor in the soft tissue or interfere with x- ray evaluations, because CaHA is visible radiographically, and that nodules were not better identified. (Although the company did not report any evidence of nodules, there were adverse event reports that could have been interpreted to be nodules.) To determine whether Radiesse implants could mimic or obscure tumors, the company performed a study of x-rays and CT scans of 58 patients who had received Radiesse injections for correction of nasolabial folds or HIV lipoatrophy, including patients who had received the first injections at least 12 months earlier. In that study, there was no evidence on CT scans that Radiesse migrates from the point of injection. Neither was there a significant risk that Radiesse would mask or mistakenly be interpreted as a benign or malignant tumor, or that the implants would prompt biopsies or further work-ups—even by radiologists who don’t know the patient has had them—because of the benign appearance and bilateral placement, according to the company. The implants are not always seen on x-rays, as with CT scans. The panel had some concerns about this issue and that the presence of Radiesse could be potentially confusing on an x-ray or CT scan and would require more follow-up. The panel also agreed that the question of migration had not been completely answered. ■ Radiesse lasts longer than hyaluronic acid fillers, so a more rigorous study is needed to achieve ‘any level of comfort regarding safety.’ Lipoatrophy Indication For approval of the lipoatrophy indication, the company presented the results of an open-label, nonrandomized, noncomparative multicenter study using Radiesse in 100 HIV-positive patients, whose mean age was 48 years and who had been receiving highly active antiretroviral therapy for at least 3 years. Three months after the final treatment, 98% of the patients were very much improved or much improved from baseline on the Global Aesthetic Improvement Scale (GAIS), the primary end point of the study (the remaining 2% were improved). GAIS ratings remained improved at 6 and 12 months, with increased skin thickness that was maintained until about 12 months. The majority of patients said they were satisfied and would recommend the treatment at all three time points. There were no unanticipated adverse events, with injection-related adverse events typical of dermal fillers, such as ecchymoses, pain, erythema, and pruritus, the most commonly observed. They were mostly mild and occurred at the time of injection or shortly afterward, and they did not last long, according to Dr. Stacey Silvers of the New York Eye and Ear Infirmary, who presented these results on behalf of BioForm. Contour irregularities occurred but were transient and quickly resolved, said Dr. Silvers, who reported no financial ties to BioForm. The nasolabial fold, split-face study compared Radiesse to Cosmoplast in the correction of nasolabial folds in 117 patients aged 31-72 years, with nasolabial folds rated 3 (a moderately deep wrinkle) or 4 (a deep wrinkle with well-defined edges) on the Lemperle Rating Scale (LRS), with 12-month safety data on 47 patients. At 3 months, nearly 85% of Radiesse-treated folds were rated as superior, based on the LRS, to the Cosmoplasttreated folds, the primary effectiveness end point. At 6 months, nearly 79% of Radiesse-treated folds were considered superior to the Cosmoplast-treated folds, 16% were equivalent, and 5% were inferior, a secondary effectiveness end point. www.finacea-us.com FINACEA is indicated for topical treatment of inflammatory papules and pustules of mild to moderate rosacea. Although some reduction of erythema which was present in patients with papules and pustules of rosacea occurred in clinical studies, efficacy for treatment of erythema in rosacea in the absence of papules and pustules has not been evaluated. FINACEA is for dermatologic use only, and not for ophthalmic, oral, or intravaginal use. FINACEA is contraindicated in individuals with a history of hypersensitivity to propylene glycol or any other component of the formulation. In clinical trials, sensations of burning/stinging/tingling occurred in 29% of patients, and itching in 11%, regardless of the relationship to therapy. Post-marketing safety—Skin: facial burning and irritation; Eyes: iridocyclitis on accidental exposure to the eye. There have been isolated reports of hypopigmentation after use of azelaic acid. Since azelaic acid has not been well studied in patients with dark complexion, these patients should be monitored for early signs of hypopigmentation. Please see brief summary of Prescribing Information on following page. Results shown are the results for one patient. Not all patients may have the same results. *FINACEA was only studied in clinical trials for 12 weeks. In the treatment of mild to moderate rosacea RESULTS MATTER Baseline Week after week after week, dermatologists and patients see the benefits of FINACEA* After 4 weeks of FINACEA bid Seeing is Believing
Page 1: COSMECEUTICAL CRITIQUE: GINSENG, PA

FDA Panel Backs Radiesse Approval, With Conditions

Create successful ePaper yourself

Delete template?

Save as template?