Pharma And Health From Ingredients To Pills: Recordati Acquired Novartis’s Isturisa and FDA Approval

On March 06, 2020, the U.S. Food and Drug Administration has announced the approval of new medication Isturisa (osilodrostat), the first and only cortisol synthesis inhibitor and a new non-surgical option for the treatment of patients with Cushing’s Disease (CD)—a rare disease in which patients' adrenal glands produce excessive levels of the hormone cortisol who cannot undergo pituitary gland surgery or have undergone the surgery but still have the disease. (1)

Isturisa (also known as osilodrostat) is a milestone and new non-surgical treatment originally developed by Novartis Pharmaceuticals but acquired by Recordati (an Italy-based European specialty pharmaceutical group) in June 2019 to treat Cushing's Disease. The drugmaker Recordati Rare Diseases Inc. is a public international specialty pharmaceutical company committed to the research and development of new specialties with a focus on treatments for rare diseases. Currently, Recordati has operations throughout the whole of Europe, including the United States of America, Canada, Russia, Turkey, North Africa, Mexico, some South American countries, Japan and Australia.

Recordati Rare Diseases is committed to making this innovative treatment available for all patients suffering from endogenous Cushing’s Syndrome (CS) worldwide and the European approval and subsequent launch is an important first step in this direction according to the drugmaker. (2)

Based on the National Institutes of Health (NIH) study, Cushing Disease is estimated to occur in 10 to 15 per million people worldwide. This disease usually occurs in adults between the ages of 20 and 50; however, children may also be affected. For unknown reasons, Cushing Disease affects females more often than males. (3)

Cushing's Disease is considered a rare condition and caused by elevated levels of a hormone called cortisol. More specifically, this disease is characterized by the hypersecretion of the adrenocorticotropic hormone (ACTH) due to a pituitary adenoma that ultimately causes endogenous hypercortisolism by stimulating the adrenal glands. (4)

Cortisol is a vital hormone that regulates metabolism and cardiovascular function and helps the body respond to stress. Excess levels of cortisol can lead to a wide variety of health issues, such as uncontrollable weight gain, central obesity (abdomen that sticks out with thin arms and legs), a round, red full face, buffalo hump (collection of fat on the back of the neck), type 2 diabetes, blood clotting disorders, thin skin and easy bruising,  striae (purple stretch marks) and weak muscles, excess body and facial hair, interrupted menstrual cycle, bone loss and fractures, hypertension (high blood pressure), kidney stones, a weakened immune system and depression. (5) In addition, there is a distinction between Cushing’s Syndrome and Cushing’s Disease. Cushing Disease is a form of Cushing Syndrome. When a pituitary gland tumor secretes excessive amounts of adrenocorticotropic hormone (ACTH), the disorder is referred to as Cushing’s Disease. When the adrenal gland produces excessive amounts of cortisol, the condition is called Cushing’s Syndrome.

The FDA’s approval of Isturisa is based on  phase 3 research data generated by the open-label clinical trial, demonstrated that Isturisa inhibits an enzyme called 11-beta-hydroxylase, preventing synthesis of cortisol in 137 adults. Most of those patients had undergone surgery that did not cure their disease or were not candidates for surgery. After 24 weeks, about half of the patients had cortisol levels within a normal range. At that point, 71 patients were entered into an 8-week withdrawal study in which they were randomly assigned to receive either Isturisa or a placebo. At the end of the withdrawal period, the FDA says 86% of patients who received the Novartis drug maintained normal cortisol levels compared to 30% of those who were given a placebo. The results have showed normalization of cortisol levels in a significant portion of adult patients with a manageable safety profile, making this a novel treatment option for patients with Cushing's Disease without surgery. (1)

Isturisa (osilodrostat) is a cortisol synthesis inhibitor indicated for the treatment of adult patients with Cushing’s Disease for whom pituitary surgery is not an option or has not been curative. The drug 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 drug response. Isturisa will be available as 1 mg, 5 mg and 10 mg film‐coated tablets.

The most common adverse drug reactions associated with Isturisa and occurring in greater than 20% of patients included adrenal insufficiency, in which the adrenal glands do not produce enough steroid hormones, fatigue, nausea, vomiting, headache, and swelling.  Other side effects such as QTc prolongation and elevations in adrenal hormone precursors may also occur in patients taking Isturisa.

Prescribing information notes that drug interactions may include:

• CYP3A4 Inhibitor: Reduce the dose of Isturisa by half with concomitant use of a strong CYP3A4 inhibitor.

• CYP3A4 and CYP2B6 Inducers: An increase of Isturisa dosage may be needed if Isturisa is used concomitantly with strong CYP3A4 and CYP2B6 inducers. A reduction in Isturisa dosage may be needed if strong CYP3A4 and CYP2B6 inducers are discontinued while using Isturisa.

Isturisa, a cortisol synthesis inhibitor, a twice-daily pill, will come with the FDA's orphan drug designation, providing 7 years of market exclusivity. The drug is expected to be commercially available in the U.S. in the second or third quarter of 2020.

Back in July 2019, Recordati acquired the worldwide rights to Isturisa (osilodrostat) from Novartis Pharmaceuticals for an upfront fee of $390 million (included rights to other drugs). On 15 January 2020, the European Commission (EU) confirmed the orphan status of Isturisa and granted marketing authorization for Isturisa in the European Union, indicated for the treatment of endogenous Cushing’s Syndrome (CS) in adults, providing 10 years of market exclusivity.

References:

1        www.fda.gov

2        https://www.recordatirarediseases.com

3        www.nih.gov

4        Endocrine. 2017 Apr; 56(1):10-18.

5        J Med Life. 2016 Jan-Mar; 9 (1):12-18.

Author Biography

Lin Zhang, Ph.D., senior director of a health care industry company in the United States. With the experience in clinical medicine, biotechnology, health industry and other fields, he is responsible for the research and development of plant medicine, functional food and health products. He was a clinician and worked for the National Cancer Institute, FDA and the National Cancer Center of Japan for many years.

About the Author:

Lin Zhang, M.D., senior director of a health care industry company in the United States. With the experience in clinical medicine, biotechnology, health industry and other fields, he is responsible for the research and development of plant medicine, functional food and health products. He was a clinician and worked for the National Cancer Institute, FDA and the National Cancer Center of Japan for many years.

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