Hormone Deficiencies

February 8, 2016

Zafgen issued results of a pivotal, double-blind, placebo-controlled, phase III trial evaluating the safety and efficacy of beloranib for Prader-Willi syndrome (PWS). The bestPWS ZAF-311 study randomized 107 patients to receive twice-weekly subcutaneous injections of either 2.4mg or 1.8mg of beloranib or placebo. Seventy-four patients completed the full 26 weeks of treatment per the trial protocol, and 27 patients completed at least 75% of the randomized treatment period prior to the suspension of dosing in the trial in October 2015. There were six patients who discontinued early. The co-primary efficacy endpoints for this trial were improvement in hyperphagia-related behaviors and reduction in body weight. Patients in the trial were on average 20 years old, had an average BMI of 40kg/m2 and an average hyperphagia total score of 16.9, consistent with moderate to severe hyperphagia, at the beginning of randomized treatment. Treatment with the 2.4mg and the 1.8mg doses of beloranib resulted in reductions of hyperphagia-related behaviors of 7 units (p=0.0001) and 6.3 units (p=0.0003) relative to placebo, respectively, as measured by the Hyperphagia Questionnaire for Clinical Trials (HQ-CT). Patients randomized to receive placebo displayed substantial (4.15%) gain in body weight over the course of the six months of randomized treatment. Patients treated with beloranib, in contrast to placebo, lost weight, with the 2.4mg dose arm displaying a 5.3% reduction from baseline, with a placebo-adjusted weight loss of 9.45%. In December 2015, the FDA placed the beloranib IND application on complete clinical hold due to an imbalance in severe venous thromboembolic events, including two patient deaths. Zafgen plans to present to the FDA the efficacy and safety data from the bestPWS ZAF-311 study, data from the phase IIb trial of beloranib in severe obesity complicated by type 2 diabetes and a proposal for a risk mitigation strategy for beloranib in PWS.

July 1, 2013

Versartis released results from a phaseIb/IIa trial of VRS-317 for the treatment of Growth Hormone Deficiency (GHD). The trial enrolled 72 naïve-to-treatment, pre-pubertal children with GHD and consisted of two stages. VRS-317 dosing began at 0.80 mg/kg, a dose shown to be safe and well-tolerated in GHD adults in a previously completed trial, with planned dose increases to 1.2mg/kg, 1.8mg/kg, 2.7mg/kg, 4mg/kg and up to 6mg/kg. The typical dose of daily rhGH in children with GHD is approximately 40mcg/kg/day. Related adverse events have been reported in 12 subjects to date and all have been mild and transient. Single doses of up to 2.7mg/kg are safe and well-tolerated. In addition, dose proportional increases in VRS-317 levels and IGF-I responses were observed, indicating the ability to select doses and dose regimens for up to once monthly dosing. The only approved growth hormone treatments require daily injections.

January 15, 2007

QuatRx announced positive results from a phase II trial of fispemifene for the treatment of androgen deficiency and related disorders in men. This randomized, double-blind, placebo-controlled trial enrolled 77 men with secondary hypogonadism, in the US. Subjects received 100, 200 and 300 mg doses of fispemifene or placebo for 28 days. Results revealed a 60%, 60% and 78% increase in testosterone levels for the 100, 200 and 300 mg fispemifene groups, respectively, while those on placebo showed a 14% increase in testosterone levels (p<0.05, p<0.01, p<0.001, respectively). In all dose-groups the mean testosterone level increased into the normal range of 300 ng/dL to 900 ng/dL. Based on the results, QuatRx plans to advance the development of fispemifene for the treatment of hormone deficiency.

September 18, 2006

Ardana announced positive preliminary results from a phase II trial of its testosterone cream for the treatment of male hypogonadism. This trial enrolled 16 men who were divided into 2 groups of 8 and randomized to receive a single daily application of testosterone cream at a dose of either 2.25g or 4.5g for 28 days. Testosterone concentrations were measured for 24 hours on the last day of the study, day 28. Preliminary efficacy analysis showed that 80% of the subjects on the lower dose treatment had testosterone levels with an average concentration of 4.74 ng/ml, well within the normal range of 3-10 ng/ml. This data indicates that only a small number of subjects would need the higher dose concentration of the cream to restore testosterone levels to the normal range. Additional phase I and II trials are ongoing and a phase III trial is being planned.

October 3, 2005

Altus Pharmaceuticals issued positive results of a phase I trial of their long-acting crystalline formulation of human growth hormone (HGH) ALTU-238, for the treatment of HGH deficiency, at the 7th joint meeting of the European Society for Paediatric Endocrinology and the Lawson Wilkins Pediatric Endocrine Society in Lyon, France. Trial data yielded pharmacokinetic and pharmacodynamic data supportive of once-weekly subcutaneous dosing, and a single-dose of the drug produced sustained serum IGF-1 levels comparable to 7 daily injections of an approved HGH formulation. This open-label study enrolled healthy adults, who received a single subcutaneous injection of the drug.

August 8, 2005

Auxilium reported top line results of a phase II trial of their androgen replacement transmucosal film, for the treatment of male hypogonadism. Preliminary data yielded evidence of efficacy, with 3 doses of the film each yielding increases in serum testosterone levels; the efficiency of absorption indicated that the lowest trial dose would be optimal for future studies. The film had a positive overall tolerability profile, and 97% of subjects indicated that the film treatment was "desirable" or "acceptable." This open-label study enrolled 69 hypogonalal men, who received daily applications of the film at one of three dose levels (5 mg, 10 mg or 15 mg).

March 21, 2005

GTx has reported positive results of a phase I trial of their non-steroidal selective androgen receptor modulator ostarine, for the treatment of andropause, sarcopenia, and other symptoms of testosterone deficiency. Trial data indicated that the drug was safe and well tolerated, with no serious dose-related or clinically significant adverse events observed. Pharmacokinetic data yielded a positive profile supportive of further development. This double-blind, placebo-controlled study enrolled 96 healthy volunteers, who received single ascending doses of the drug. The company, based on these results, announced plans to initiate a phase I multiple ascending dose study of the drug in April 2005.

September 20, 2004

Auxilium Pharmaceuticals has reported the results of a phase IV study of their topical testosterone therapy Testim, for the treatment of hypogonadism in men unable to achieve symptom amelioration with AndroGel, another topical testosterone therapeutic. The study found that Testim therapy was effective in treating symptoms of hypogonadism, significantly improving sexual function and satisfaction, compared with men remaining on a comparable dose of AndroGel. In addition, a significantly higher portion of subjects receiving Testim did not require dose escalation to achieve results at the end of the study period, compared with AndroGel. The study enrolled a total of 151 hypogonadal men who were refractory to or insufficiently served by AndroGel therapy; these subjects were randomized to receive either continued treatments with AndroGel or Testim once daily for 4 weeks.

July 12, 2004

Zonagen announced positive preliminary results of their phase I/II study of Androxal (clomiphene), an estrogen antagonist, for the treatment of testosterone deficiency in men. Results indicated that the drug was safe and well tolerated, and produced significant increases in testosterone levels over placebo. The trial randomized a total of 70 hypogonadal men into one of 6 treatment arms: one of three doses of oral Androxal, one of two doses of topic Androgel (a currently approved topical gel for testosterone deficiency), or placebo. All subjects received daily dosing for two weeks to analyze safety and tolerability, and half of the subjects in each trial arm were examined on days 1 and 14 for pharmacokinetics and efficacy in increasing testosterone levels. Androxal was found to be comparable to placebo for all adverse events, and it produced significant, dose dependent increases in testosterone levels during a 7-10 day observation period following administration at all dose levels. Zonagen indicated that they would announce final results, including comparative data for Androxal vs. Androgel, later this year.

July 7, 2003

Neurocrine Biosciences reported positive results from a phase I trial investigating NBI-42902, a GnRH receptor antagonist for the treatment of hormone dependent diseases. Results demonstrated that NBI-42902 was absorbed rapidly after oral administration and was found to be safe and well tolerated. Gonadal suppression was achieved and resulted in suppression of estrogen to anticipated therapeutic levels. The randomized, double blind, placebo-controlled, parallel group study enrolled 18 healthy pre-menopausal women. Subjects were assigned to three groups, NBI-42902 75 mg once a day, NBI-42902 37.5 mg twice a day or placebo. Data indicated suppression of luteinizing hormone and follicle-stimulating hormones as expected based on data from previous studies.