Cushing’s syndrome (CS) is a rare condition. It’s health consequences can be severe, leading to visceral adiposity, muscle weakness, depression, insulin resistance, diabetes, blood clots, reduced immune system, and cardiovascular disease.
A portion of patients diagnosed with CS has Cushing’s disease (CD). In Cushing’s disease, the root cause of hypercortisolism is a pituitary tumor producing excessive ACTH hormone. The preferred treatment is pituitary surgery. Unfortunately, in a small subset of patients, the operation is not successful or indicated.
To address the health concerns for individuals who are not responsive or candidates for pituitary tumor resection, the FDA has now approved a backup treatment via the oral drug Isturisa.
Isturisa, taken twice daily, is a potent inhibitor of 11-β-hydroxylase, a key enzyme in cortisol production. Side effects can include relative adrenal insufficiency, swelling, nausea, vomiting, and headaches. Clinical studies have shown that about 50% of patients respond to therapy.
Isturisa is an excellent addition to the arsenal of combating refractory Cushing’s disease.
Dr. Tashko
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FDA APPROVAL
DRUG THERAPY
March 2020
Background
The U.S. Food and Drug Administration today approved Isturisa (osilodrostat) oral tablets for adults with Cushing’s disease who either:
- Adrenal insufficiency,
- Headache,
- Vomiting,
- Nausea,
- Fatigue and
- Edema (swelling caused by fluid retention).
Hypocortisolism (low cortisol levels), QTc prolongation (a heart rhythm condition) and elevations in adrenal hormone precursors (inactive substance converted into a hormone) and androgens (hormone that regulates male characteristics) may also occur in people taking Isturisa.
Isturisa is taken by mouth twice a day, in the morning and evening as directed by a health care provider. After treatment has started, a provider may re-evaluate dosage, depending upon the patient’s response.
Isturisa received Orphan Drug Designation, which is a special status granted to a drug intended to treat a rare disease or condition.
- High blood pressure
- Obesity
- Type 2 diabetes
- Blood clots in the legs and lungs
- Bone loss and fractures
- Weakened immune system and
- Depression.
- Patients may have thin arms and legs, a round red full face, increased fat around the neck, easy bruising, striae (purple stretch marks) and weak muscles.
Isturisa
Isturisa’s safety and effectiveness for treating Cushing’s disease among adults was evaluated in a study of 137 adult patients (about three-quarters women) with a mean age of 41 years. The majority of patients either had undergone pituitary surgery that did not cure Cushing’s disease or were not surgical candidates.
In the 24-week, single-arm, open-label period, all patients received a starting dose of 2 milligrams (mg) of Isturisa BID that could be increased every two weeks up to 30 mg BID. At the end of this 24-week period, about half of patients had cortisol levels within normal limits.
After this point, 71 patients who did not need further dose increases and tolerated the drug for the last 12 weeks entered an eight-week, double-blind, randomized withdrawal study where they either received Isturisa or a placebo (inactive treatment). At the end of this withdrawal period, 86% of patients receiving Isturisa maintained cortisol levels within normal limits compared to 30% of patients taking the placebo.
The most common side effects reported in the clinical trial for Isturisa were:
- Adrenal insufficiency,
- Headache,
- Vomiting,
- Nausea,
- Fatigue and
- Edema (swelling caused by fluid retention).
Hypocortisolism (low cortisol levels), QTc prolongation (a heart rhythm condition) and elevations in adrenal hormone precursors (inactive substance converted into a hormone) and androgens (hormone that regulates male characteristics) may also occur in people taking Isturisa.
Isturisa is taken by mouth twice a day, in the morning and evening as directed by a health care provider. After treatment has started, a provider may re-evaluate dosage, depending upon the patient’s response.
Isturisa received Orphan Drug Designation, which is a special status granted to a drug intended to treat a rare disease or condition.
- Cannot undergo pituitary gland surgery or
- Have undergone the surgery but still have the disease.
Cushing’s disease is a rare disease in which the adrenal glands make too much of the cortisol hormone. Isturisa is the first FDA-approved drug to directly address this cortisol overproduction by blocking the enzyme known as 11-beta-hydroxylase and preventing cortisol synthesis.
“The FDA supports the development of safe and effective treatments for rare diseases, and this new therapy can help people with Cushing’s disease, a rare condition where excessive cortisol production puts them at risk for other medical issues,” said Mary Thanh Hai, M.D., acting director of the Office of Drug Evaluation II in the FDA’s Center for Drug Evaluation and Research. “By helping patients achieve normal cortisol levels, this medication is an important treatment option for adults with Cushing’s disease.”
Cushing’s disease is caused by a pituitary tumor that releases too much of a hormone called adrenocorticotropin, which stimulates the adrenal gland to produce an excessive amount of cortisol. The disease is most common among adults between the ages of 30-50, and it affects women more often than men by three times.
Cushing’s disease can cause significant health issues, such as:
- High blood pressure
- Obesity
- Type 2 diabetes
- Blood clots in the legs and lungs
- Bone loss and fractures
- Weakened immune system and
- Depression.
- Patients may have thin arms and legs, a round red full face, increased fat around the neck, easy bruising, striae (purple stretch marks) and weak muscles.
Isturisa
Isturisa’s safety and effectiveness for treating Cushing’s disease among adults was evaluated in a study of 137 adult patients (about three-quarters women) with a mean age of 41 years. The majority of patients either had undergone pituitary surgery that did not cure Cushing’s disease or were not surgical candidates.
In the 24-week, single-arm, open-label period, all patients received a starting dose of 2 milligrams (mg) of Isturisa BID that could be increased every two weeks up to 30 mg BID. At the end of this 24-week period, about half of patients had cortisol levels within normal limits.
After this point, 71 patients who did not need further dose increases and tolerated the drug for the last 12 weeks entered an eight-week, double-blind, randomized withdrawal study where they either received Isturisa or a placebo (inactive treatment). At the end of this withdrawal period, 86% of patients receiving Isturisa maintained cortisol levels within normal limits compared to 30% of patients taking the placebo.
The most common side effects reported in the clinical trial for Isturisa were:
- Adrenal insufficiency,
- Headache,
- Vomiting,
- Nausea,
- Fatigue and
- Edema (swelling caused by fluid retention).
Hypocortisolism (low cortisol levels), QTc prolongation (a heart rhythm condition) and elevations in adrenal hormone precursors (inactive substance converted into a hormone) and androgens (hormone that regulates male characteristics) may also occur in people taking Isturisa.
Isturisa is taken by mouth twice a day, in the morning and evening as directed by a health care provider. After treatment has started, a provider may re-evaluate dosage, depending upon the patient’s response.
Isturisa received Orphan Drug Designation, which is a special status granted to a drug intended to treat a rare disease or condition.