EMEA rejects recombinant Human Growth Hormone for AIDS-related wasting

1 June 2003. Related: Other news.

Simon Collins, HIV i-Base

The European Medicines Evaluation Agency (EMEA) has rejected Serono’s application to license its formulation of recombinant Human Growth Hormone, a compound with anabolic effects, (rHGH, non-proprietary name: Somatropin; tradename: Serostim) for AIDS-related wasting syndrome.

Serostim was designated as an orphan drug in August 2000, which allows for additional support from the European agency and reduced costs, for compounds to treat very low incidence diseases.

The reasons given for rejection by the Committee for Proprietary Medicinal Products (CPMP, the agencies scientific committee) included:

• Difficulty to identify a target population due to the heterogeneity in terms of body composition and antiretroviral (ARV) options included in Study GF 9037
• Doubts about the clinical relevance of the primary endpoints studied of improved work output and lean body mass (LBM). Although the questionnaire on the Quality of Life (QoL) showed improvements across all the domains it is still unclear what kind of a benefit might be expected from treatment with Serostim in a clinical setting.
• Long-term efficacy data under controlled conditions are lacking. These are considered necessary to determine the maintenance of the effect of Serostim or the rebound phenomenon, whether the therapy should be intermittent or systematic and whether there would be a need for dose adjustment.
• There is concern about the long-term safety profile of Serostim in the context of repeated courses of treatment in AIDS patients.

The drug received accelerated approval from the FDA for AIDS-wasting in the United States in July 1996.

Serono disagree with the EMEA interpretation of the trial results (which were presented at the IAS World AIDS Conference in Barcelona last year, Abstract ThPeB7352, and others).

Source: EMEA Press Release and Summary of Opinion

Links:

Serono Press Release
http://www.serono.com/media/stories2003/20030430_en.jsp?major=4&minor=1

Useful article on Human Growth Hormone
http://www.thebody.com/sfaf/winter03/hgh.html

Comment

The main problem with this study was the diverse patient population, with a minority of patients fullfilling the definition of true wasting. r-HGH has a clear anabolic effect in most study participants and this can reverse or stop the loss of lean body mass in HIV-positive patients who have experienced weight loss.

Side effects include induction of diabetes mellitus in patients with abnormal glucose tolerance and arthralgia, especially at the 6mg/day dose. Lipoatrophy may worsen due to subcutaneous fat loss.

Serono is also trying to get rHGH approved for lipodystrophy – reversal of buffalo hump and abdominal visceral fat have been reported during treatment, but symptoms generally return within a few months of discontinuing treatments.