November 10, 1997

Dear Doctor:

This letter is to inform you of findings from two recently concluded studies of the use of recombinant somatropin (Genotropin) for treatment of acute catabolism in critically ill patients. The findings and recommendations do not apply to the use of Genotropin in the approved indication of treatment of children who have growth failure due to inadequate secretion of endogenous growth hormone.

In two large Phase III prospective, randomized, double-blind, placebo-controlled trials conducted in Europe, the effects of recombinant somatropin in critically ill patients in the intensive care unit (ICU) with acute catabolism have been studied. An inclusion criterion was ICU care following 1) open heart surgery, 2) abdominal surgery, 3) multiple accidental trauma, or 4) acute respiratory failure. The patients were given a dose regimen of 16 IU (5.3 mg) or 24 IU (8mg) per day dependent on body weight of less than or greater than 60 kg. The maximum treatment time was 21 days.

A total of 532 patients have been included in these two studies. Two hundred fifty-nine (259) patients were treated with somatropin, 264 patients with placebo and 9 patients were untreated. The results of the two studies were similar and showed a significantly higher mortality in the somatropin-treated patients. For the two studies combined, the mortality rate was 18.2% in placebo-treated patients (48/264) and 41.7% in the somatropin-treated patients (108/259). Further assessment of the data to develop a clear understanding of the reasons behind these differences is ongoing.

We recommend that further use of recombinant somatropin (Genotropin) for treatment of acute catabolism, including pre- and post-operative treatment, critically ill patients and burn patients be stopped immediately.

Again, we would like to reiterate that this recommendation to stop treatment does not apply to the use of Genotropin for the approved indication of treatment of children who have growth failure due to inadequate secretion of endogenous growth hormone. More than 10 years of clinical experience and extensive data provided by large clinical trials and long-term follow-up programs have shown that Genotropin treatment in this indication is safe and effective.

If you have additional question regarding these studies, please contact Medical and Drug Information at 800-253-8600, extension 3-8244.

John R. Luderer, M.D.
Vice President, Medical Affairs

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