By Mary Welch

Genentech Inc. and Alkermes Inc. reported positive results from a Phase III study of Nutropin Depot, their sustained-release formulation of somatropin (recombinant human growth hormone), and the companies said they plan to submit a new drug application (NDA) to the FDA early next year.

Phase III trials of 74 pre-pubescent patients in 27 centers in the U.S. showed the drug was safe, tolerable and effective in treating children with growth hormone deficiency.

"They increased significantly from their baseline growth rate and achieved a positive change of the patients' standardized height," said Betsy Rosenberg, spokeswoman for South San Francisco-based Genentech. "They experienced a 'catch-up' growth, and in general their growth rate did increase significantly, both on the once-a-month and twice-a-month dosage regimen."

The primary efficacy endpoint was linear growth rate at six months, annualized. All patients were given the option of continuing treatment after completion of the six-month study, and a large percentage stayed with the program. Results will be released at a yet-to-be-determined scientific meeting, no later than early summer.

Nutropin Depot uses Cambridge, Mass.-based Alkermes' ProLease injectable sustained-release drug delivery system, which encapsulates the compound in biodegradable microspheres. The affected children — estimated at about 20,000 in the U.S. — now must take daily injections of a growth hormone.

ProLease lasts longer than drug-delivery microcarriers such as liposomes, Alkermes said. At the heart of Alkermes' sustainable-release system is a polymer called poly (lactide-co-glycolide), or PLG for short. The protein is first turned into a lyophilized powder, which is then suspended in a polymer solution in organic solvent. Next, the suspension is atomized to create droplets. The droplets are frozen with liquid nitrogen, which undergoes a solvent extraction that removes the polymer solvent. Finally, they are filtered and vacuum-dried. The result is porous polymer particles that contain freeze-dried protein particles dispersed throughout.

The alliance between Alkermes and Genentech dates back to 1996, when Genentech agreed to pay up to $30 million to continue the clinical development of ProLease sustained drug technology. A year later, the collaboration was expanded, said Richard Pops, CEO of Alkermes.

"I don't remember how much the deal was expanded financially," Pops said. "It was a big deal, and we're at the point where milestones are no longer significant economic bonuses."

For Genentech, the success of Nutropin Depot solidifies, and may eventually expand, its hold on the growth hormone market. The company's first marketed product was Protropin (somatrem for injection), a recombinant growth hormone. Since then, its family of growth hormones has grown to include Protropin, Nutropin (somatropin for injection) and Nutropin AQ (somatropin for injection), all produced using recombinant DNA technology. All three are approved for children.

Sales of the three totaled $52.9 million for the third quarter 1998, down from $57 million for the same period last year, primarily due to fluctuations in distributors' ordering patterns. (See BioWorld Today, Oct. 15, 1998, p. 1.)

Both companies probably will start Nutropin Depot trials on adults at some point, Pops said. "With adults, it's not a matter of trying to increase height, but there are some other manifestations of [growth hormone deficiency]," he said. "A lot of adults don't take growth hormones because they don't want to deal with daily shots."

For Alkermes, this would be the first NDA for the company and "based on past results and having a partner like Genentech that has shown confidence in us — we have been able to attract other partners and have a number of product development candidates," Pops said.

Alkermes has two other collaborations, both with Johnson & Johnson (J&J) companies. The latest is a $30 million deal with the New Brunswick, N.J.-based J&J's R.W. Johnson Pharmaceutical Research Institute, which will seek to apply ProLease to the blood-booster erythropoietin (EPO), which is licensed from Amgen Inc., of Thousand Oaks, Calif. The companies intend to enter Phase I trials soon, Pops said. (See BioWorld Today, Jan. 23, 1998, p. 1.)

Alkermes signed a $20 million deal with another J&J subsidiary, Janssen Pharmaceutica NV, of Beerse, Belgium, that paired Medisorb, a ProLease technology that applies to small molecules, with an unidentified drug. The companies expect to enter Phase III trials by the end of the year.

Genentech's stock (NYSE:GNE) closed Thursday at $70.25, down $0.25. Alkermes' shares (NASDAQ:ALKS) ended the day at $19.312, up $4.812. *