ROCKLAND, Mass., Aug. 17 /PRNewswire-FirstCall/ -- Serono announced today positive results of a pivotal Phase III trial of Serono’s recombinant human growth hormone (r-hGH) for the treatment of HIV-associated Adipose Redistribution Syndrome (HARS) at the XVI International AIDS Conference in Toronto, Canada. Results of the trial were presented as a late-breaker session on August 17th during the International AIDS Conference.
Serono submitted a supplemental New Drug Application (sNDA) to the US Food and Drug Administration (FDA) during the second quarter of 2006.
“The findings from the HARS study provide promising news for the HIV community and for people living with HARS, a metabolic condition for which there is currently no approved drug treatment,” said Paul Lammers, M.D., M.Sc., Chief Medical Officer for Serono, Inc. “Visceral fat accumulation and lipid changes are concerns for HIV patients who are living longer due to advances in antiretroviral therapy. We are pleased that the study met all pre-specified primary and major secondary efficacy endpoints and we look forward to working with the FDA during the review process.”
The HARS study, a Phase III, double-blind, placebo-controlled study, was designed to evaluate recombinant human growth hormone as a potential therapy for reducing abnormal accumulations of visceral fat. In HARS study patients, r-hGH 4 mg daily for 12 weeks significantly reduced visceral adipose tissue (VAT), trunk fat, non-HDL cholesterol, and improved pre-specified health-related quality of life outcomes. Maintenance therapy for 24 weeks with a lower dose of r-hGH helped sustain the clinical benefits.
“The results of the HARS study indicate that Serono’s recombinant human growth hormone has a potential role in the treatment of HIV-infected patients who have increased visceral adipose tissue,” said lead presenter and investigator, Carl Grunfeld, M.D.,PhD, Professor of Medicine, Chief, Metabolism and Endocrine Sections, SF Veterans Affairs Medical Center, University of California at San Francisco. “This is an important finding for a condition that has a significant impact on HIV-infected patients in the U.S. who suffer from the consequences of increased visceral fat.”
Results of the HARS Phase III Trial
326 patients were randomized into the trial to determine if daily administration of r-hGH as treatment for the abnormal fat accumulation and distribution associated with HARS reduces visceral adipose tissue as compared to placebo. Patients that had abnormal glucose at the time of screening into the trial were excluded from the study.
The primary endpoint was change in cross-sectional VAT area on CT scan measured at vertebral level L4-L5. Key secondary endpoints included reduction in trunk fat, the impact of reduction in VAT on body image and patient reported outcomes associated with quality of life, and changes in lipid parameters, including non-HDL cholesterol.
In the first induction phase of the study, patients were randomly assigned to receive either r-hGH 4 mg daily, or placebo for 12 weeks. In the second placebo-controlled maintenance phase of the study, r-hGH was administered as 2 mg on alternate days for 24 weeks to assess the ability of a lower dose regimen to sustain improvements in VAT.
At the end of the induction phase, the mean change (plus or minus SD) in visceral adipose tissue area was -32.6 plus or minus 37.9cm2 on r-hGH and +0.5 plus or minus 34.5cm2 on placebo (p<0.001). Compared to placebo, patients on r-hGH induction therapy had decreased trunk fat, limb fat and non-HDL cholesterol (p value less than or equal to 0.023).
Among patients who lost VAT from weeks 1-12 on r-hGH 4 mg daily, during the entire treatment period (baseline to week 36), patients on r-hGH maintenance therapy sustained reductions in VAT (-26.6 plus or minus 43.9cm2) from baseline. Patients on placebo sustained a smaller reduction in VAT (-10.0 plus or minus 39 cm2). By 36 weeks, there were no changes in limb fat from baseline in either group. At 36 weeks, non-HDL-C remained decreased on r-hGH maintenance therapy, and on placebo to a lesser degree.
Patient Reported Outcomes data were also collected and those results will be presented at upcoming scientific meetings.
Patients treated with r-hGH had normal fasting glucose at screening. Treatment with r-hGH for 12 weeks was associated with mild to moderate increases in mean blood glucose concentrations. Other common adverse events reported in patients with HARS included edema, joint and muscle pain, all known to be associated with r-hGH treatment.
About HARS
HARS, a subset of HIV-associated lipodystrophy, is a condition affecting HIV patients in which there is maldistribution of body fat characterized by central fat accumulation (lipohypertrophy) with or without lipoatrophy (subcutaneous fat depletion primarily in the face and limbs). In HARS patients, abnormal fat may additionally accumulate in the upper body subcutaneous area such as dorsocervical area (i.e. “buffalo hump”). These changes may be accompanied by metabolic disturbances including insulin resistance, glucose intolerance, and dyslipidemia, as well as body image distress.
Recombinant human growth hormone is not currently approved by the FDA for the treatment of HARS.
About Recombinant Human Growth Hormone
Recombinant human growth hormone (r-hGH) is human growth hormone produced by recombinant DNA technology. Serono’s r-hGH products are indicated for the treatment of pediatric growth hormone deficiency, adult growth hormone deficiency, HIV wasting or cachexia and for the treatment of short bowel syndrome.
Growth hormone should be used with caution in patients with insulin resistance, glucose intolerance, diabetes, and in women who are pregnant or nursing. The most commonly reported adverse events include mild injection-site reactions, moderate muscle and joint pain, and edema/swelling. Patients with a history of hyperglycemia or other risk factors for glucose intolerance or pancreatitis should be monitored closely. Use of growth hormone is contraindicated in treatment of patients in intensive care units due to complications following open-heart surgery or abdominal surgery, multiple accidental trauma or acute respiratory failure; patients with active neoplasia; and patients with known hypersensitivity to growth hormone.
Full prescribing information for Serono’s FDA approved products, including important safety information, is available at http://www.seronousa.com.
Forward-looking statements
Some of the statements in this press release are forward looking. Such statements are inherently subject to known and unknown risks, uncertainties and other factors that may cause actual results, performance or achievements of Serono S.A. and affiliates to be materially different from those expected or anticipated in the forward-looking statements. Forward-looking statements are based on Serono’s current expectations and assumptions, which may be affected by a number of factors, including those discussed in this press release and more fully described in Serono’s Annual Report on Form 20-F filed with the U.S. Securities and Exchange Commission on February 28, 2006. These factors include any failure or delay in Serono’s ability to develop new products, any failure to receive anticipated regulatory approvals, any problems in commercializing current products as a result of competition or other factors, our ability to obtain reimbursement coverage for our products, the outcome of any government investigations and litigation. Serono is providing this information as of the date of this press release, and has no responsibility to update the forward-looking statements contained in this press release to reflect events or circumstances occurring after the date of this press release.
About Serono, Inc.
Serono, Inc., located in Rockland, Massachusetts, is the US affiliate of Serono S.A., a global biotechnology leader, headquartered in Geneva, Switzerland. The Company has seven recombinant products, Rebif(R) (interferon beta-1a), Gonal-f(R) (follitropin alfa for injection), Luveris(R) (lutropin alfa), Ovidrel Prefilled Syringe(R) (choriogonadotropin alfa injection), Serostim(R) [somatropin (rDNA origin) for injection], Saizen(R) [somatropin (rDNA origin) for injection] and Zorbtive(TM) [somatropin (rDNA origin) for injection] on the market in the U.S.
Serono S.A. is the world leader in reproductive health and has strong market positions in neurology, metabolism and growth. Serono S.A.'s research programs are focused on growing these businesses and on establishing new therapeutic areas, including oncology and autoimmune diseases.
In 2005, Serono, whose products are sold in over 90 countries, achieved worldwide revenues of US$2,586.4 million. Reported net loss in 2005 was US$106.1 million, reflecting a charge of US$725 million taken relating to the settlement of the US Attorney’s Office investigation of Serostim. Excluding this charge as well as other non-recurring items, adjusted net income grew 28.4% to US$565.3 million in 2005. Bearer shares of Serono S.A., the holding company, are traded on the virt-x (SEO) and its American Depositary Shares are traded on the New York Stock Exchange (SRA).
Package inserts for Serono’s US marketed products are available at http://www.seronousa.com or by calling 1-888-275-7376.
For more information, please contact: Serono, Inc., Rockland, MA Media Relations: Investor Relations: Stacie Madden Tel: +1 781 681 2552 Tel: +1 781 681 2496 Fax: +1 781 681 2912 stacie.madden@serono.comhttp://www.seronousa.com
Serono, Inc.
CONTACT: Stacie Madden of Serono, Inc., Media Relations, +1-781-681-2496,stacie.madden@serono.com, or Serono, Inc. Investor Relations,+1-781-681-2552
Web site: http://www.seronousa.com/
