GENENTECH NUTROPIN CLEARED BY FDA FOR hGH DEFICIENCY MARCH 8 AS LILLY'S HUMATROPE LOSES ORPHAN EXCLUSIVITY; FOUR OTHER GROWTH HORMONE PRODUCTS PENDING

Genentech's Nutropin (somatropin) received IDA approval for treatment of short stature caused by human growth hormone deficiency on March 8, the day Lilly's Humatrope (somatropin) lost orphan drug exclusivity for that indication.

Nutropin is Genentech's second growth hormone product in the hGH deficiency market. The company's Protropin, approved in 1985, holds about 75% of the market with 1993 sales of $216 mil. Protropin differs from Humatrope and Nutropin by one amino acid and was granted a separate orphan exclusivity on approval 15 months before Humatrope.

In November, Nutropin was approved by FDA for treatment of short stature associated with chronic renal insufficiency ("The Pink Sheet" Nov. 22, 1993, T&G-6). The NDA for hGH deficiency was first submitted in December 1986 but was rejected by FDA in April 1988 due to the orphan exclusivity accorded to Humatrope.

Nutropin is "indicated for the long-term treatment of children who have growth failure due to a lack of endogenous growth hormone secretion," labeling states. The recommended dose for hGH deficiency is .30 mg/kg per week administered by daily subcutaneous injection. The approved chronic renal insufficiency dosage is slightly higher, at .35 mg/kg.

The price to wholesalers for Nutropin is the same as for Protropin -- $350 for two 5 mg vials. The average wholesale price also is the same for both growth hormone products at $420 for two 5 mg vials.

The Nutropin label contains several revisions to reflect the new indication. The precautions section states that "changes in thyroid hormone laboratory measurements may develop during Nutropin treatment in children who lack adequate endogenous growth hormone secretion." Labeling advises that "patients should have periodic thyroid function tests."

In the Nutropin approval letter to Genentech, IDA reminds the company that "validation of the regulatory methods has not been completed." At "the present time, it is the policy of the center not to withhold approval because the methods are being validated. Nevertheless, we expect your continued cooperation to resolve any deficiencies that may occur," the approval letter states. IDA initiated validation of Genentech's recombinant DNA production methodology following the approval of Nutropin in November.

Four other companies have NDAs pending for growth hormones that were blocked by Lilly's orphan exclusivity: Bio-Technology General (Biotropin), Novo-Nordisk (Norditropin), Serono (Saizen) and Kabi.

Genentech has initiated patent litigation against BTG and Novo, and also has pending litigation against Lilly. At the end of February, the International Trade Commission denied a Genentech request for a preliminary injunction to prohibit BTG from importing hGH. The ITC patent infringement case with BTG is set to go to trial at the end of March or in early April.

In remarks before securities analysts in September, Genentech said it would seek to distinguish Protropin from "generic" growth hormones by emphasizing its marketing history and follow-up information gathered from the National Cooperative Growth Study, and by supplying patient education materials and other services with the drug ("The Pink Sheet" Sept. 27, 1993, T&G-4). The NCGS will be expanded to include Nutropin, Genentech said.