FDA panel supports injectable midface filler

GAITHERSBURG, MD. – A Food and Drug Administration advisory panel unanimously recommended approval of an injectable filler specifically for use in the midface.

At a May 2 meeting, the members of the FDA’s General and Plastic Surgery Devices Panel supported approval of Allergan’s Juvéderm Voluma XC (Voluma) for the correction of age-related volume loss in the midface. The FDA usually follows the recommendations of its advisory panels, which are not binding.

The meeting was held for the panel to discuss, make recommendations, and vote on information related to the premarket approval application for Voluma. Voluma is a biodegradable dermal filler that combines low- and high-molecular-weight hyaluronic acid (20 mg/mL) and 0.3% lidocaine in phosphate-buffered saline.

This new formulation distinguishes Voluma from other injectable products, noted Joseph Nielsen, Ph.D., a biologist with the FDA’s Center for Drug Evaluation and Research.

Voluma’s combination of high- and low-molecular-weight hyaluronic acid creates a thicker product with a jamlike consistency that is designed for deeper injections, said Dr. Rui Avelar, chief medical officer for Allergan. Voluma is indicated specifically for deep injections (subcutaneous and/or supraperiosteal) to correct age-related volume loss in the midface. No products are currently approved in the United States for this indication, although Voluma is approved in 65 countries, including Canada and Australia.

The approval was based on data from a randomized clinical trial. The study population included adults aged 35-65 years (mean age, 55 years). Approximately 80% of the patients were women, more than half were white, and 44% were Fitzpatrick skin types IV, V, and VI. A total of 235 patients were randomized to immediate treatment with Voluma, and 47 served as nontreatment controls to receive injections 6 months later; 208 treatment patients and 36 nontreatment controls had complete data for evaluation at 6 months.

Primary effectiveness was based on the blinded live evaluation of two investigators using the Mid-Face Volume Deficit Scale (MFVDS), a 0-5 point scale approved and validated for the study. Significant response was defined as at least a 1-point change in the MFVDS. In addition, three-dimensional imaging was used to assess changes in volume. Imaging data were not collected from nonresponders.

At 6 months, 86% of the treatment patients and 35% of the untreated controls met the response criteria. In addition, the evaluators rated 82% of treatment patients and 22% of controls as "improved" or "much improved," compared with pretreatment photos using the Global Aesthetic Improvement Scale, and 93% of treated patients rated themselves as improved or much improved, compared with pretreatment photos.

The average initial treatment was 5.2 mL, and 82% of treated patients received an optional touch-up injection of an average of 2 mL 30 days after the first treatment. The injection techniques were consistent with the methods used for other currently available fillers.

Individuals were excluded from the study if they had permanent or semipermanent facial aesthetic procedures, temporary facial aesthetic procedures within the washout period, midface volume loss unrelated to age, or very thin skin in the midface.

Greater baseline volume deficit was a stronger predictor than age of the volume of filler injected, although both factors were associated with a greater volume injected, said Todd Gross, Ph.D., a biostatistician for Allergan.

However, age, volume of product injected, and tunneling technique were associated with an increased risk of adverse events, said Dr. Janette Alexander, an FDA medical officer.

A total of 33% of the participants reported treatment-related adverse events. Five patients had late-onset adverse events; three of these were deemed severe and device related. The three severe treatment-related events involved lumps at the injection sites, all of which were treated with hyaluronidase, Dr. Alexander said.

The other two serious events included a death caused by stroke 1 year after treatment, and an ischemic optic neuropathy that the FDA could not definitely deem device related.

Approximately 78% of subjects reported an injection site response, but the majority of these resolved within 30 days. Injection site responses included firmness, lumps or bumps, tenderness, swelling, pain, bruising, redness, and discoloration. Approximately 20% of treated patients reported firmness or lumps/bumps persisting longer than 30 days.

The safety profile appears similar to that of other hyaluronic acid fillers except for the duration of firmness and lumps/bumps, and the occurrence of late adverse events, Dr. Alexander said.

No increase in risk of adverse events was observed in darker skin types, said Alvin Van Orden, of the FDA’s division of biostatistics.

The panel agreed that the postapproval study of 12 months’ follow-up proposed by Allergan is adequate, but extra attention should be paid to the subset of patients with darker skin, who might respond differently to the treatment, said panel chair Dr. Joseph LoCicero III, of the State University of New York, Brooklyn.

The panelists’ comments in support of their votes included acknowledgment of the safety profile and the reversibility of the product if needed, and the benefits of having an FDA-approved product for volume enhancement.

During their discussion, the panel members also agreed that setting upper limits on filler volume, age, and relative skin thickness should be left to clinical judgment, and not contraindicated.

Members of FDA advisory panels have been cleared of potential conflicts of interest related to the products under discussion prior to the meeting.

[email protected]

GAITHERSBURG, MD. – A Food and Drug Administration advisory panel unanimously recommended approval of an injectable filler specifically for use in the midface.

At a May 2 meeting, the members of the FDA’s General and Plastic Surgery Devices Panel supported approval of Allergan’s Juvéderm Voluma XC (Voluma) for the correction of age-related volume loss in the midface. The FDA usually follows the recommendations of its advisory panels, which are not binding.

The meeting was held for the panel to discuss, make recommendations, and vote on information related to the premarket approval application for Voluma. Voluma is a biodegradable dermal filler that combines low- and high-molecular-weight hyaluronic acid (20 mg/mL) and 0.3% lidocaine in phosphate-buffered saline.

This new formulation distinguishes Voluma from other injectable products, noted Joseph Nielsen, Ph.D., a biologist with the FDA’s Center for Drug Evaluation and Research.

Voluma’s combination of high- and low-molecular-weight hyaluronic acid creates a thicker product with a jamlike consistency that is designed for deeper injections, said Dr. Rui Avelar, chief medical officer for Allergan. Voluma is indicated specifically for deep injections (subcutaneous and/or supraperiosteal) to correct age-related volume loss in the midface. No products are currently approved in the United States for this indication, although Voluma is approved in 65 countries, including Canada and Australia.

The approval was based on data from a randomized clinical trial. The study population included adults aged 35-65 years (mean age, 55 years). Approximately 80% of the patients were women, more than half were white, and 44% were Fitzpatrick skin types IV, V, and VI. A total of 235 patients were randomized to immediate treatment with Voluma, and 47 served as nontreatment controls to receive injections 6 months later; 208 treatment patients and 36 nontreatment controls had complete data for evaluation at 6 months.

Primary effectiveness was based on the blinded live evaluation of two investigators using the Mid-Face Volume Deficit Scale (MFVDS), a 0-5 point scale approved and validated for the study. Significant response was defined as at least a 1-point change in the MFVDS. In addition, three-dimensional imaging was used to assess changes in volume. Imaging data were not collected from nonresponders.

At 6 months, 86% of the treatment patients and 35% of the untreated controls met the response criteria. In addition, the evaluators rated 82% of treatment patients and 22% of controls as "improved" or "much improved," compared with pretreatment photos using the Global Aesthetic Improvement Scale, and 93% of treated patients rated themselves as improved or much improved, compared with pretreatment photos.

The average initial treatment was 5.2 mL, and 82% of treated patients received an optional touch-up injection of an average of 2 mL 30 days after the first treatment. The injection techniques were consistent with the methods used for other currently available fillers.

Individuals were excluded from the study if they had permanent or semipermanent facial aesthetic procedures, temporary facial aesthetic procedures within the washout period, midface volume loss unrelated to age, or very thin skin in the midface.

Greater baseline volume deficit was a stronger predictor than age of the volume of filler injected, although both factors were associated with a greater volume injected, said Todd Gross, Ph.D., a biostatistician for Allergan.

However, age, volume of product injected, and tunneling technique were associated with an increased risk of adverse events, said Dr. Janette Alexander, an FDA medical officer.

A total of 33% of the participants reported treatment-related adverse events. Five patients had late-onset adverse events; three of these were deemed severe and device related. The three severe treatment-related events involved lumps at the injection sites, all of which were treated with hyaluronidase, Dr. Alexander said.

The other two serious events included a death caused by stroke 1 year after treatment, and an ischemic optic neuropathy that the FDA could not definitely deem device related.

Approximately 78% of subjects reported an injection site response, but the majority of these resolved within 30 days. Injection site responses included firmness, lumps or bumps, tenderness, swelling, pain, bruising, redness, and discoloration. Approximately 20% of treated patients reported firmness or lumps/bumps persisting longer than 30 days.

The safety profile appears similar to that of other hyaluronic acid fillers except for the duration of firmness and lumps/bumps, and the occurrence of late adverse events, Dr. Alexander said.

No increase in risk of adverse events was observed in darker skin types, said Alvin Van Orden, of the FDA’s division of biostatistics.

The panel agreed that the postapproval study of 12 months’ follow-up proposed by Allergan is adequate, but extra attention should be paid to the subset of patients with darker skin, who might respond differently to the treatment, said panel chair Dr. Joseph LoCicero III, of the State University of New York, Brooklyn.

The panelists’ comments in support of their votes included acknowledgment of the safety profile and the reversibility of the product if needed, and the benefits of having an FDA-approved product for volume enhancement.

During their discussion, the panel members also agreed that setting upper limits on filler volume, age, and relative skin thickness should be left to clinical judgment, and not contraindicated.

Members of FDA advisory panels have been cleared of potential conflicts of interest related to the products under discussion prior to the meeting.

[email protected]

GAITHERSBURG, MD. – A Food and Drug Administration advisory panel unanimously recommended approval of an injectable filler specifically for use in the midface.

At a May 2 meeting, the members of the FDA’s General and Plastic Surgery Devices Panel supported approval of Allergan’s Juvéderm Voluma XC (Voluma) for the correction of age-related volume loss in the midface. The FDA usually follows the recommendations of its advisory panels, which are not binding.

The meeting was held for the panel to discuss, make recommendations, and vote on information related to the premarket approval application for Voluma. Voluma is a biodegradable dermal filler that combines low- and high-molecular-weight hyaluronic acid (20 mg/mL) and 0.3% lidocaine in phosphate-buffered saline.

This new formulation distinguishes Voluma from other injectable products, noted Joseph Nielsen, Ph.D., a biologist with the FDA’s Center for Drug Evaluation and Research.

Voluma’s combination of high- and low-molecular-weight hyaluronic acid creates a thicker product with a jamlike consistency that is designed for deeper injections, said Dr. Rui Avelar, chief medical officer for Allergan. Voluma is indicated specifically for deep injections (subcutaneous and/or supraperiosteal) to correct age-related volume loss in the midface. No products are currently approved in the United States for this indication, although Voluma is approved in 65 countries, including Canada and Australia.

The approval was based on data from a randomized clinical trial. The study population included adults aged 35-65 years (mean age, 55 years). Approximately 80% of the patients were women, more than half were white, and 44% were Fitzpatrick skin types IV, V, and VI. A total of 235 patients were randomized to immediate treatment with Voluma, and 47 served as nontreatment controls to receive injections 6 months later; 208 treatment patients and 36 nontreatment controls had complete data for evaluation at 6 months.

Primary effectiveness was based on the blinded live evaluation of two investigators using the Mid-Face Volume Deficit Scale (MFVDS), a 0-5 point scale approved and validated for the study. Significant response was defined as at least a 1-point change in the MFVDS. In addition, three-dimensional imaging was used to assess changes in volume. Imaging data were not collected from nonresponders.

At 6 months, 86% of the treatment patients and 35% of the untreated controls met the response criteria. In addition, the evaluators rated 82% of treatment patients and 22% of controls as "improved" or "much improved," compared with pretreatment photos using the Global Aesthetic Improvement Scale, and 93% of treated patients rated themselves as improved or much improved, compared with pretreatment photos.

The average initial treatment was 5.2 mL, and 82% of treated patients received an optional touch-up injection of an average of 2 mL 30 days after the first treatment. The injection techniques were consistent with the methods used for other currently available fillers.

Individuals were excluded from the study if they had permanent or semipermanent facial aesthetic procedures, temporary facial aesthetic procedures within the washout period, midface volume loss unrelated to age, or very thin skin in the midface.

Greater baseline volume deficit was a stronger predictor than age of the volume of filler injected, although both factors were associated with a greater volume injected, said Todd Gross, Ph.D., a biostatistician for Allergan.

However, age, volume of product injected, and tunneling technique were associated with an increased risk of adverse events, said Dr. Janette Alexander, an FDA medical officer.

A total of 33% of the participants reported treatment-related adverse events. Five patients had late-onset adverse events; three of these were deemed severe and device related. The three severe treatment-related events involved lumps at the injection sites, all of which were treated with hyaluronidase, Dr. Alexander said.

The other two serious events included a death caused by stroke 1 year after treatment, and an ischemic optic neuropathy that the FDA could not definitely deem device related.

Approximately 78% of subjects reported an injection site response, but the majority of these resolved within 30 days. Injection site responses included firmness, lumps or bumps, tenderness, swelling, pain, bruising, redness, and discoloration. Approximately 20% of treated patients reported firmness or lumps/bumps persisting longer than 30 days.

The safety profile appears similar to that of other hyaluronic acid fillers except for the duration of firmness and lumps/bumps, and the occurrence of late adverse events, Dr. Alexander said.

No increase in risk of adverse events was observed in darker skin types, said Alvin Van Orden, of the FDA’s division of biostatistics.

The panel agreed that the postapproval study of 12 months’ follow-up proposed by Allergan is adequate, but extra attention should be paid to the subset of patients with darker skin, who might respond differently to the treatment, said panel chair Dr. Joseph LoCicero III, of the State University of New York, Brooklyn.

The panelists’ comments in support of their votes included acknowledgment of the safety profile and the reversibility of the product if needed, and the benefits of having an FDA-approved product for volume enhancement.

During their discussion, the panel members also agreed that setting upper limits on filler volume, age, and relative skin thickness should be left to clinical judgment, and not contraindicated.

Members of FDA advisory panels have been cleared of potential conflicts of interest related to the products under discussion prior to the meeting.

[email protected]