Five years after its European approval, last week the FDA's General &
Plastic Surgery Devices Advisory Panel finally recommended for approval poly-L-lactic acid for the treatment of facial wasting in people with HIV-related lipodystrophy. The US brand name for New-Fill will be Sculptra, and it will be marketed by Aventis/Dermik, who own the worldwide patent. New-Fill will continue to be available in the UK from MediPhill, the sole UK distributors.
Unlike in Europe, however, Sculptra is only recommended for approval for the treatment of HIV-associated fat loss, and not for general cosmetic surgery. Aventis/Dermik will be seeking FDA approval for this purpose at future date, once well-controlled, prospective clinical trials begins in pursuit of a cosmetic indication. Dermik expects those trials to begin before the end of the year.
The panel were convinced enough by the five studies presented to assess safety and efficacy in people with HIV-associated fat loss, and this led to a 9-0 vote in favour of conditional approval specifically for HIV-associated lipoatrophy.
However, the panel have only approved Sculptra subject to Dermik conducting a post-approval study lasting between two and five years, in order to ascertain whether Sculptra is safe and effective in HIV-positive of different ethnicities and genders. The panel also urged the FDA to go beyond strong labeling warnings to prevent Sculptra from being used off-label (i.e. for general cosmetic enhancement), and recommended that a thorough training programme take place for clinicians to ensure the correct use of Sculptra, which may greatly reduce the adverse events reported in the three US trials (see below).
The VEGA study from France, reported here, London’s Chelsea & Westminster Hospital’s New-Fill study, reported here, as well as three new US studies were presented at the FDA hearings. All were single centre studies and none of them were randomised, controlled, or blinded, which is very unusual, given that most FDA drug approvals require much more rigorous trials.
The three new US studies examining the effect of New-Fill on facial lipoatrophy in HIV-positive people that were presented at the hearings were APEX-001 and -002 and Hermosa Beach. APEX-001 and -002 focused on patient and investigator satisfaction ratings, and no skin thickness measurements were used in these studies. The Hermosa Beach study, however, did include facial thickness measurements.
In APEX-001, 100 HIV-positive individuals with HIV-related facial lipoatrophy — average age 44, HIV-positive for an average of 14 years — received between one and six treatments (average number = 3) of between 1-8 cc of New-Fill per treatment session. The main adverse events — which were considered mild — were small nodules under the skin, invisible to the eye, but which could be felt upon physical examination. Six nodules were reported in 85 individuals at three weeks, and 39 nodules were reported in 70 patients seen after 12 months. There was, however, high patient satisfaction, with an average score of 8.8 out of 10. There was also a high investigator rating — from 3.2 to 1.36 (a lower score is better).
APEX-002 also included 100 HIV-positive individuals with similar demographic features to APEX-001. The mild adverse events reported here were soreness at the injection site in 19 individuals and six individuals with nodules. Additionally, two participants experienced transient fever. Again, there were high patient satisfaction scores reported: ranging from 3.71 to under 1 (a lower score is better).
The Hermosa Beach trial reported similar results to the APEX trials, with addition of skin thickness measurements. At six months facial skin thickness increased by an average of 6mm.
The FDA panel conclusions
The FDA panel found that “in general, the majority of treatment related events are mild pain, bruising and swelling at the injection site.” Subcutaneous nodules were experienced by a higher percentage (up to 50%) than reported in the UK and French studies. However, no major adverse events were reported.
The FDA were particularly impressed by both the VEGA and C&W skin thickness analyses — statistically significant (pNew-Fill.
Quality of life improvements were shown in all studies.
Further information on this website
New-Fill: facial improvements sustained for two years - news story
New Fill injections improve facial appearance, reduce anxiety, within 3 months - news story
AIDS Treatment Update Dec 2003/Jan 2004 - New-Fill special edition (pdf file)