US approves and Europe rejects Serostim (recombinant growth hormone) for treatment of HIV-related wasting

On 29 August 2003 the US Food and Drug Administration (FDA) granted full approval for Serostim (somatropin; recombinant growth hormone for injection), which is indicated for the treatment of HIV patients with wasting or cachexia to increase lean body mass and body weight, and improve physical endurance.

FDA granted Serostim accelerated approval in 1996, a special regulatory status granted by the FDA for approval of a drug that is used to treat patients with serious or life-threatening illnesses, and provides meaningful therapeutic benefit over any existing treatments.

Under the terms of the accelerated approval, Serono conducted a multi-centre, confirmatory placebo-controlled study with Serostim. Data from this trial substantiate previous study findings of increased lean body mass and improvement in physical strength. In addition, patients in this study perceived an improvement in their wasting symptoms and in quality of life.Since 1996, rHGH has been widely prescribed in the US, although this has been through insurance-based healthcare and against the background of concerns for the high cost.

Within a week of the US decision the EMEA in Europe confirmed that it will not grant approval for the same drug for the same indication.

In April 2003, the European Medicines Evaluation Agency rejected Serono’s application to market Serostim for AIDS-related wasting syndrome. Serono formally appealed this decision in July, and following an expert meeting on 2 September the EMEA announced that the original April decision would be upheld and marketing authorisation would not be recommended.

Comment

The FDA approval was a consequence of the presentation of additional data from a recent trial by Serono as requested in 1996 when they granted conditional approval.

In contrast, in Europe Serono had no approval for the use for Serostim in wasting. The data from the recent multicenter trial showed a clear anabolic effect of Serostim in the study population as assessed by bicycle exercise.

However two major concerns were expressed by the EMEA with regard to this trial: first most patients included did not seem to fulfill the criteria of HIV-wasting, and second, the translation of bicycle workout into clinical benefit was difficult to accomplish. Other concerns raised were a negative impact of Serostim on lipoatrophy.

In addition the issue of a relapse of wasting after discontinuation of Serostim remained unresolved by the present data. The current transatlantic split will keep Serostim on the market, but will make it available for European patients with wasting only under exceptional circumstances, if at all.