A tepid reception to new top-line phase III data on the long-acting growth hormone (GH) somatrogon nudged Opko Health Inc. shares (NASDAQ:OPK) about 4 cents higher to $2.13 Monday, leaving it overshadowed by competitor Ascendis Pharma A/S, the developer of Transcon-hGH. Ascendis' shares (NASDAQ:ASND) rose 4.5% to $103.36.

Opko's trial found once-weekly somatrogon noninferior to partner Pfizer Inc.'s daily Genotropin (somatropin) in pre-pubertal children with GH deficiency. But the result seemed only good enough to support a "minority market share for somatrogon in the long-acting pediatric GH category," J.P. Morgan analyst Jessica Fye wrote. "Heading into these results, we saw the superior phase III results for Transcon GH setting a high bar for somatrogon," she said.

Fye's team, which holds an "overweight" rating on Ascendis, is projecting a 15% peak market share for somatrogon in the pediatric long-acting GH market vs. a 50% share for Ascendis' therapy. A 24% share is projected for the other major long-acting GH entrant from Novo Nordisk A/S, somapacitan. But, at least initially, that candidate is being pursued as a long-acting treatment for adults with GH deficiency. Norditropin, Novo's branded somatropin, is the market leader, according to Cortellis.

To test somatrogon's mettle, Opko enrolled 224 treatment-naïve children with GH deficiency in a trial that randomized them evenly to receive either somatrogon dosed once weekly or daily Genotropin. On the primary endpoint, the least square mean was higher in the somatrogon group (10.12 cm/year) than in the somatropin group (9.78 cm/year), putting the treatment difference (somatrogon – somatropin) in height velocity (cm/year) at 0.33 with a two-sided 95% confidence interval of the difference of (-0.39, 1.05).

Somatrogon was generally well-tolerated in the study and comparable to that of somatropin dosed once daily with respect to the types, numbers and severity of the adverse events observed between the treatment arms, the partners said. But neither specific results on the AEs somatrogon-treated patients experienced nor data on trunk fat mass, a metric that ruffled somatrogon-watchers in an earlier phase III study of somatrogon, were disclosed. (See BioWorld, Jan. 3, 2017.)

Still, both Opko and Pfizer hailed the results as favorable and encouraging for those with GH deficiency, a rare disease characterized by the inadequate secretion of growth hormone from the pituitary gland and affects one in about 4,000 to 10,000 people. "We believe somatrogon represents a significant advance in the treatment of children with GHD compared to the current standard of one injection per day that could enhance a patient's adherence to treatment and quality of life," said Opko CEO Phillip Frost.

In addition to the primary efficacy and safety endpoints, Opko reported the change in height standard deviation scores at six and 12 months, key secondary endpoints, were higher in the somatrogon cohort vs. the Genotropin cohort. Also, at six months, change in height velocity, another key secondary endpoint, was higher in the somatrogon once-weekly cohort in comparison to the somatropin once-daily cohort.

Neither Opko nor Pfizer provided representatives to further discuss the data.

Miami-based Opko has been collaborating with Pfizer on its long-acting GH candidate since at least December 2014, when the pair struck a deal to co-develop the therapy, a product originated by Prolor Biotech Inc. Prolor's carboxyl terminal peptide technology, key to the molecule's extended half-life, underpinned Opko's $540.6 million all-stock acquisition of the company in 2013. The Pfizer deal arrived not long after, with a $295 million up-front fee, plus the promise of up to $275 million in regulatory milestones for Opko. (See BioWorld, April 25, 2013, and Dec. 16, 2014.)

Should the program succeed, it would help Pfizer extend its presence in pediatric endocrinology and growth disorders, a platform it has continued building in recent months, most recently with its $810 million acquisition of Therachon AG, putting a spotlight on that company's achondroplasia therapy, recifercept. (See BioWorld, May 9, 2019.)

But with plenty of additional competition in the wings, including earlier-stage entrants such as Toolgenexine Inc.'s long-acting human GX-H9 and Transcon-hGH on track for a planned BLA in the first half of 2020 and an MAA in the second half of that year, it seems likely that somatrogon will face some stiff competition. (See BioWorld, July 3, 2019.)