Opko Health Inc.'s $540.6 million all-stock acquisition of Prolor Biotech Inc. paid off Monday as Pfizer Inc. grabbed an exclusive license to the Prolor-developed long-acting human growth hormone (hGH) for $295 million up front, plus up to $275 million in regulatory milestones. (See BioWorld Today, April 25, 2013.)

The deal, built around an hGH formulation using Prolor's carboxyl terminal peptide technology (CPT), could bring patients an opportunity to shift to weekly injections instead of daily jabs while helping both Opko and Pfizer generate new revenue.

The hormone is intended for the long-term treatment of children and adults with growth failure due to inadequate secretion of endogenous growth hormone, a $3.5 billion market opportunity growing 5 percent annually, according to Opko. "By reducing the number of injections, our technology can improve patient compliance," said Opko's CEO, Phillip Frost.

"Long-acting growth hormone is the first innovation in the GHD space in 20 years," said Geno Germano, group president of Pfizer's global innovative pharma division. Opko's hGH-CTP would be complementary to Pfizer's existing Genotropin franchise as well, he said.

The experimental therapy, called hGH-CTP, is Opko's lead candidate. It's currently in testing for the treatment of growth hormone deficiency (GHD) in adults and children, as well as for the treatment of growth failure in children born small for their gestational age (SGA).

Miami-based Opko will continue to lead the program's clinical development under the deal, shouldering the cost of studies for adult and pediatric GHD and pediatric SGA. Pfizer will cover development costs for any additional indications, the cost of post-marketing studies and commercialization expenses for all indications. It will also lead the manufacturing activities covered by the global development plan.

Opko also is eligible to receive initial royalty payments for the adult GHD indication. But upon launch of hGH-CTP for pediatric GHD, the royalties would transition to gross profit sharing for both hGH-CTP and Pfizer's Genotropin.

With Pfizer's Genotropin (recombinant somatropin) sales trending downward to $534 million during the nine months ended Sept. 28 vs. $570 million for the comparable year-ago period, the deal gives it a chance to build up the franchise with a new more convenient product. Opko, meanwhile, gains the opportunity to add therapeutics revenue to its existing diagnostic and lab services business. The deal is expected to close during the first quarter of 2015.

Opko is testing hGH-CTP in an ongoing phase III study in adults for hGH-CTP and a phase II trial in pediatric patients. In June, the company announced positive interim six-month results from a phase II dose-finding study evaluating the safety and efficacy of hGH-CTP for GHD in children. All three once-weekly doses tested resulted in what Opko called "strong catch-up growth" during the six-month treatment period, with annualized increases in height of more than 12 cm. The therapy has orphan drug status in the U.S. and Europe for both adults and children with GHD.

Applications of Opko's CTP technology to other proteins in Pfizer's portfolio are out of scope, said Pfizer spokesman Steven Danehy.

A CROWDED FIELD

Should New York-based Pfizer and Opko or any of the long-acting hGH programs gain approval, they'll face a large market of daily subcutaneous rhGH injection products, including Novo Nordisk's Norditropin, Eli Lilly and Co.'s Humatrope, Roche AG unit Genentech Inc.'s Nutropin-AQ, Merck Serono's Saizen, Teva Pharmaceutical Industries Ltd.'s Tev-tropin, Sandoz GmbH's Omnitrope and LG Life Science's Valtropin.

The race to be the first to gain approval for a long-acting hGH also is crowded, with competitive programs under way including Redwood City, Calif.-based Versartis Inc.'s VRS-317 for the treatment of GHD, Aileron Therapeutics Inc.'s ALRN-5281 and Copenhagen, Denmark-based Ascendis Pharma A/S advancing a candidate, too.

Versartis recently completed a phase IIa study of VRS-317 and plans to initiate a phase III trial of the therapy in early 2015. But the company is realistic about the odds for success in the space, noting in a recent regulatory filing that "many attempts have been made to develop sustained-release formulations of rhGH," and that many have failed, including for example, Nutropin Depot, a long-acting form of rhGH developed by Genentech Inc. that used Alkermes' Prolease injectable extended-release drug delivery system. It was approved by the FDA in 1999 and withdrawn from the market in 2004 "due to the significant resources required to continue manufacturing and commercializing the product," Versartis said.

LIFETYLE APPLICATIONS AHEAD?

Opko is optimistic about the future for hGH-CTP, noting in a recent regulatory filing that hGH "has been proven to promote a number of lifestyle benefits including weight loss, increased energy levels, enhanced sexual performance, improved cholesterol, younger, tighter, thicker skin and reduced wrinkles and cellulite." The company expects the hGH market "to expand significantly" as it moves beyond therapeutic treatment to include the treatment of such lifestyle issues.

Opko shares (NYSE:OPK) rose 68 cents, or 8.3 percent, to close at $8.86 on Monday. Pfizer (NYSE:PFE) shares fell 9 cents, to $30.86.