LILLY'S HUMATROPE MAY BE "CLINICALLY SUPERIOR" TO PROTROPIN, FDAer SAYS

Executive Summary

The reduced antigenicity of Lilly's Humatrope (methionyl-free recombinant human growth hormone) makes that product "quite probably" clinically superior to Genentech's Protropin, according to Solomon Sobel, director of FDA's Metabolism & Endocrine Drug Division. Sobel's assessment of the significance of the one less amino acid in the Lilly product is part of a deposition by the FDAer in the Genentech vs. FDA suit over the orphan drug approval of Humatrope on March 8. Sobel's testimony goes beyond the FDA permitted claims for Lilly's products in approved labeling. "I and FDA are persuaded," Sobel told the D.C. Federal Court on March 6, "that Lilly has demonstrated that its product is less antigenic than Protropin. I base this conclusion on assays that I and other FDA scientists believe to have been accurate and comparable." Sobel explained the jump from less antigenic to clinically superior stating that "a less antigenic compound may be safer." He added: "At the very least, it is quite likely that the less antigenic compound carries with it a smaller risk of therapeutic failure than a product with greater antigenicity." Sobel's assessment was reiterated by Wayne Moore, MD, a professor of pediatrics at the University of Kansas Medical Center, in another deposition solicited by Lilly. "I am familiar with the phenomenon of inhibiting antibodies that prevent certain drugs from achhieving the desired effect in the body," Moore stated. He noted: "I have treated a patient who developed such antibodies to pituitary-derived human growth hormone and experienced a pronounced decrease in growth rate. Given that somatrem (Protropin) appears to have a higher incidence of antibody production than somatropin (Humatrope), I believe that somatrem is more likely to produce growth-inhibiting antibodies." Moore ended by asserting that he would recommend the Lilly form to other pediatric endocrinologists over the Genentech version. The testimonials from FDA and Moore represent the downside of Genentech's legal challenge to the orphan approval for Humatrope. Especially in the FDA situation, Genentech has forced the agency to go further in its statement of the differences between Protropin and Humatrope. To Genentech's claims that Lilly's drug was approved with less testing requirements than Protropin, Sobel responded that the Lilly product was viewed by FDA as "identical to the naturally produced growth hormone . . . and thus . . . replacement therapy in a well-documented deficiency state." Sobel explained that the 30-patient control group required for Protropin studies was due to "serious concerns about the frequency of loss of efficacy of Protropin due to blocking antibodies."