SERONO SAIZEN HUMAN GROWTH HORMONE APPROVED WITH THREE-TIMES WEEKLY DOSING SCHEDULE; SOMATROPIN PRODUCT LABELING CARRIES HYPOTHYROIDISM PRECAUTION

Serono's Saizen (somatropin) will be marketed with a dosing schedule of three injections per week for children with growth hormone insufficiency following FDA approval Oct. 8.

The three-times-weekly dosing schedule is less frequent than that for Genentech's Nutropin, which is administered daily, but similar to the original human growth hormone products, Genentech's Protropin and Lilly's Humatrope.

The recommended dosage for Saizen for treatment of growth hormone insufficiency is .06 mg/kg (approximately .18 IU/kg) administered three times per week by subcutaneous or intramuscular injection.

Saizen is identical to Serostim, Serono's growth hormone product approved on Aug. 23 for AIDS wasting. Serostim is administered at daily doses of 4 mg to 6 mg for adults. Serono committed to the AIDS community to cap the annual price of Serostim at $36,000 per patient ("The Pink Sheet" Sept. 2, T&G-4). Serono is awaiting approval of another product for hGH insufficiency, Geref (sermorelin), which was recommended for approval in February 1995.

The company has not announced a price for Saizen; however, it is likely to be comparable to that of Nutropin, which has an average wholesale price of $210 per 5 mg vial. The recommended dose for Nutropin is .3 mg/kg per week. Pharmacia & Upjohn's Genotropin, which was launched earlier this year, is priced at an AWP of $210 for 5.8 mg, with a recommended dose of .16 to .24 mg/kg per week divided into six to seven injections.

"Saizen [somatropin (rDNA origin) for injection] is indicated for the long-term treatment of children with growth failure due to inadequate secretion of endogenous growth hormone," labeling states. The hGH product is not approved for the indications of treatment of children with chronic renal insufficiency or adults with somatropin-deficiency, an indication Humatrope received in August ("The Pink Sheet" Aug. 12, T&G-2).

Saizen labeling carries a precaution concerning hypothyroidism and recommends: "Thyroid hormone determinations should be performed periodically during Saizen administration and thyroid hormone replacement should be initiated when indicated."

Other adverse events noted in Saizen labeling include "hypoglycemia, seizures, exacerbation of pre-existing psoriasis and disturbances in fluid balance," which are not on the Nutropin labeling. Genotropin labeling includes "lipoatrophy; headache; hematuria, hypothyroidism; [and] mild hyperglycemia" among its adverse events.

Saizen joins Nutropin and Genotropin as the third somatropin product to be marketed since orphan exclusivity of Humatrope for the indication of hormone deficiency in children expired in March 1994. The NDA for Saizen was originally filed in August 1987 but was blocked by Lilly's exclusivity. The NDA became "approvable" on April 22.

Two other somatropin products that have been approved but have been blocked from marketing by Genentech manufacturing process patents are Novo Nordisk's Norditropin and Bio-Technology General's Bio-Tropin. Appeals are pending in those cases ("The Pink Sheet" April 15, T&G-3). Genentech recently expanded its complaint against Novo Nordisk in Brooklyn federal court to assert that the Danish company's recombinant production of insulin also infringes Genentech's process patents.

Saizen is supplied in 2 vials of 5 mg or 6 mg of the product with 2 vials of 10 mL bacteriostatic water for injection. Genentech markets a ready-to-use liquid 10 mg/vial injectable form of somatropin, Nutropin AQ, for which it gained approval in December. Genotropin is available in an Intra-Mix two-chamber cartridge, which contains drug and water for injection.