Novo Nordisk's Â Norditropin Approved for Treatment of Children with Short Stature Associated with Turner Syndrome
PRINCETON, N.J., Sept. 21 -- Novo Nordisk today announced that Norditropin(R) (somatropin [rDNA origin] injection) received approval from the U.S. Food and Drug Administration (FDA) for the treatment of children with short stature associated with Turner syndrome. Turner syndrome is a rare chromosomal condition caused by complete or partial absence of the second sex chromosome (X chromosome) in females. This occurs in approximately 1 in 2,500 live female births, and in as many as 10 percent of all miscarriages worldwide. Short stature is the most common feature associated with Turner syndrome affecting the majority of patients (90 - 100 percent depending on the chromosomal abnormalities).
"Treatment of short stature in girls with Turner syndrome is the second new indication granted this summer for Norditropin, which recently received an approval to treat children with short stature associated with Noonan syndrome," said Martin Soeters, president of Novo Nordisk Inc. "Novo Nordisk is committed to our biopharmaceutical business unit, and we will continue to conduct research in rare disorders where there are currently treatment gaps."
This FDA approval signifies advancement in dosing capabilities, giving physicians the option of dosing at higher than existing treatment options. Results from a pivotal clinical trial illustrated that treatment with Norditropin at the higher dosing level of .067 mg/kg/day resulted in 80 percent of Turner syndrome patients reaching a normal adult height compared to only 53 percent at a lower dosing level.
"I know first hand from my practice that short stature can be a social and self image concern for girls with Turner syndrome," said Judith Ross, M.D., Professor, Department of Pediatrics at Thomas Jefferson University, Philadelphia. "Clinical data for Norditropin in girls with Turner syndrome show for the first time that a higher dose Norditropin treatment regimen results in growth to a height that is considered normal compared to the general population. This higher dose option gives physicians more dosing flexibility and a greater chance of successfully treating short stature."
About Turner Syndrome
Turner syndrome is a rare chromosomal disorder of females characterized by short stature and the lack of sexual development at puberty. Among affected females, physical features may include a short neck with a webbed appearance, heart defects, kidney abnormalities and various other malformations. Several medical problems occur more frequently in individuals with Turner syndrome than in the general population, including a heightened incidence of osteoporosis, cardiac malfunction diabetes and an increased risk of ear and hearing disorders. However, there is variability in the degree to which girls with Turner syndrome are affected by any of its manifestations.
Clinical Features and Complications
Many characteristic features are associated with Turner syndrome. Their presence and severity vary greatly from individual to individual and can include
-- Narrow, high-arched palate (roof of the mouth) -- Misshapen ears and other ear disorders -- Low hairline -- Webbed neck -- Broad chest -- Scoliosis (curvature of the spine) -- Cubitus valgus (arms that curve out slightly at the elbows) -- Heart Defects
Norditropin(R) (somatropin [rDNA origin] injection) is indicated for the treatment of children with short stature associated with Turner syndrome, the treatment of children with short stature associated with Noonan syndrome, and treatment of children with growth failure due to inadequate secretion of endogenous growth hormone and for replacement of endogenous growth hormone in adults with growth hormone deficiency (GHD) who meet either of the following two criteria:
1) Adult Onset: Patients who have GHD, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma; or 2) Childhood Onset: Patients who were growth hormone deficient during childhood as a result of congenital, genetic, acquired, or idiopathic causes.
In general, confirmation of the diagnosis of adult GHD in both groups usually requires an appropriate growth hormone stimulation test.
Important Safety Information
Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses or in patients with active proliferative or severe non- proliferative diabetic retinopathy. Norditropin should not be used in patients with known hypersensitivity to somatropin or any of its excipients.
Somatropin should not be used or should be discontinued with any evidence of active malignancy. Patients with preexisting malignancy should be monitored carefully for any progression or reoccurrence.
Somatropin should not be used to treat patients with acute critical illness due to complications following open heart or abdominal surgery, multiple accidental trauma or acute respiratory failure as increased mortality may occur.
Deaths have been reported in patients with Prader-Willi syndrome who are severely obese or have severe respiratory impairment and are treated with somatropin. Unless patients with Prader-Willi syndrome also have a diagnosis of GHD, Norditropin is not indicated for the treatment of patients who have growth failure due to genetically confirmed Prader-Willi syndrome.
Blood glucose levels should be monitored periodically as treatment with somatropin may decrease insulin sensitivity. Patients with preexisting diabetes or glucose intolerance should be monitored closely during somatropin therapy. Doses of insulin or oral agents may need to be adjusted for patients with diabetes on somatropin therapy.
Intracranial hypertension (IH) with papilledema, visual changes, headache, nausea and/or vomiting has been reported in a small number of patients treated with somatropin products. Symptoms usually occurred within the first eight (8) weeks after initiation of somatropin therapy and generally resolve after cessation of therapy or a reduction of the somatropin dose. Funduscopic examination should be performed routinely before initiating and periodically during the course of somatropin therapy. If papilledema is observed by funduscopy during somatropin treatment, treatment should be discontinued.
Pediatric patients may develop slipped capital femoral epiphyses more frequently if they have endocrine disorders or during rapid growth. Any child having onset of a limp or complaints of hip or knee pain during somatropin therapy should be carefully evaluated. Progression of scoliosis can occur in patients who experience rapid growth. Somatropin has not been shown to increase the occurrence of scoliosis.
In patients with GHD, central (secondary) hypothyroidism may first become evident or worsen during somatropin treatment. Patients treated with somatropin should therefore have periodic thyroid function tests and thyroid hormone replacement therapy should be initiated or adjusted as needed.
Somatropin inhibits 11Beta-hydroxysteroid dehydrogenase type 1 (11BetaHSD-1) in adipose/hepatic tissue, and may significantly impact the metabolism of cortisol and cortisone. In patients treated with somatropin, previously undiagnosed central (secondary) hypoadrenalism may be unmasked requiring glucocorticoid replacement therapy. In addition, patients treated with glucocorticoid replacement therapy especially with cortisone acetate and prednisone for previously diagnosed hypoadrenalism may require an increase in their maintenance or stress doses.
Careful monitoring is advisable when somatropin is administered in combination with other drugs known to be metabolized by CP450 liver enzymes (e.g., corticosteroids, sex steroids, anticonvulsants, cyclosporine) or other hormone replacement therapy.
The safety and effectiveness of Norditropin in patients age 65 years and older has not been evaluated in clinical studies. Elderly patients may be more sensitive to the actions of somatropin and may be more prone to develop adverse reactions.
Common somatropin-related adverse reactions include injection site reactions/rashes, lipoatrophy and headaches, glucose intolerance, fluid retention and unmasking of latent central hypothyroidism.
Most serious adverse reactions include intracranial hypertension, diabetic retinopathy, glucose intolerance, slipped capital femoral epiphysis, progression of preexisting scoliosis, sudden death in pediatric patients with Prader-Willi syndrome with risk factors including severe obesity, history of upper airway obstruction or sleep apnea and unidentified respiratory infection, intracranial tumors as a 2nd tumor in patients who had been treated for a 1st neoplasm.
In clinical studies wherein children with Turner Syndrome were treated, the most frequently reported adverse events were common childhood diseases including influenza-like illness, otitis media, upper respiratory tract infection, otitis externa, gastroenteritis and eczema.
Patients with Turner syndrome should be evaluated carefully for otitis media and other ear disorders since these patients have an increased risk of ear and hearing disorders. Somatropin treatment may increase the occurrence of otitis media in patients with Turner Syndrome.
For more information including the prescribing information for Norditropin, please visit norditropin-us.com.
About Novo Nordisk
Novo Nordisk is a healthcare company and a world leader in diabetes care. The company has the broadest diabetes product portfolio in the industry, including the most advanced products within the area of insulin delivery systems. In addition, Novo Nordisk has a leading position within areas such as hemostasis management, growth hormone therapy and hormone replacement therapy. Novo Nordisk manufactures and markets pharmaceutical products and services that make a significant difference to patients, the medical profession and society. With headquarters in Denmark, Novo Nordisk employs more than 23,600 employees in 79 countries, and markets its products in 179 countries. Novo Nordisk's B shares are listed on the stock exchanges in Copenhagen and London. Its ADRs are listed on the New York Stock Exchange under the symbol 'NVO'. For more information, visit novonordisk.com.