Data from the Phase III LINC-3 study, published in Lancet Diabetes & Endocrinology, demonstrate that Isturisa® (osilodrostat) rapidly decreases mean urinary free cortisol (mUFC) in patients with Cushing’s disease.

PUTEAUX, France–(BUSINESS WIRE)–Recordati Rare Diseases announces today that Lancet Diabetes & Endocrinology has published positive results from the Phase III LINC-3 pivotal study of Isturisa®, recently approved for the treatment of endogenous Cushing’s syndrome in adults. Patients with Cushing’s disease, the most common form of endogenous Cushing’s syndrome, have an increased risk of significant comorbidities, including cardiovascular and cerebrovascular diseases as a result of excessive cortisol levels.¹ Data from the large LINC-3 study, which enrolled 137 patients with Cushing’s disease, demonstrate that Isturisa® rapidly reduces mUFC and sustains this reduction alongside improvements in comorbidities, clinical signs and patients’ quality of life over 48 weeks.

“The exciting data, published today, underscore the efficacy and safety of Isturisa® in a prospective setting, and represent a significant advance for the management of patients with Cushing’s disease, a serious and potentially life-threatening rare condition,” said Rosario Pivonello, MD, Professor of Endocrinology at the Federico II University of Naples, Italy. “I would like to thank all the patients who participated in the LINC-3 study, and their families, who have helped to bring this new and welcome treatment option to this underserved patient population.”

The LINC-3 study met its primary endpoint, with significantly more patients maintaining normal mUFC with Isturisa® without a dose increase than placebo (86% vs 29%; P<0.0001) following 8 weeks of randomized withdrawal (week 34). Further analysis of patients’ mUFC response found:

• Over half (53%) of patients achieved the key secondary endpoint of a normal mUFC after an initial 24 weeks of open-label treatment with Isturisa®, without any dose increase after week 12
• Majority (72%) of patients had normal mUFC at week 12, and two-thirds (66%) of patients had normal mUFC at the end of the 48-week study
• Almost all (96%) patients achieved normal mUFC at some point during the study, with a median time to first complete response of 41 days

Decreases in mUFC levels during treatment with Isturisa® were accompanied by improvements in clinical signs and cardiovascular-related risk factors (weight, BMI, blood glucose, blood pressure, and total cholesterol). Isturisa® is well tolerated, with the most common adverse effects in LINC-3 being nausea (42%), headache (34%), fatigue (28%) and adrenal insufficiency (28%).

“The publication of these data in Lancet Diabetes & Endocrinology confirms Isturisa® as an effective new treatment option for patients with Cushing’s syndrome,” said Andrea Recordati, CEO. “Following the recent approval of Isturisa® in the US and EU, we are excited to bring Isturisa® to all of those patients who need it. (Read more…)”

The full manuscript can be accessed online at:

http://www.thelancet.com/journals/landia/article/PIIS2213-8587(20)30240-0/fulltext

About Cushing’s syndrome

Cushing’s syndrome is caused by an inappropriate and chronic exposure to excessive levels of cortisol. The source of this excess of cortisol can be endogenous or exogenous (ie medication).² When the excess cortisol production is triggered by a pituitary adenoma (ie. a tumor of the pituitary gland located in the brain) secreting excess adrenocorticotropic hormone (ACTH), the condition of the patient is defined as Cushing’s disease and comprises about 70% of Cushing’s syndrome cases.^2,3 It is a rare, serious and difficult-to-treat disease that affects approximately one to two patients per million per year. Prolonged exposure to elevated cortisol levels is associated with considerable morbidity, mortality and impaired quality of life as a result of complications and comorbidities.⁴ Normalization of cortisol levels is therefore a primary objective in the treatment of Cushing’s syndrome.⁵

About LINC-3

LINC-3 is a prospective, multicentre, 48-week trial with an 8-week, double-blind, randomized withdrawal phase to evaluate the safety and efficacy of Isturisa® in patients with Cushing’s disease. The primary endpoint in the LINC-3 trial is the proportion of patients randomized to Isturisa® and placebo, separately, at Week 26 with a mUFC ≤ULN at the end of the 8-week randomized withdrawal period (Week 34), without a dose increase during this period. The key secondary endpoint is the proportion of enrolled patients with a mUFC ≤ULN after an initial 24 weeks of open-label treatment with Isturisa® without any dose increase after Week 12. LINC-3 involved 137 patients with persistent or recurrent Cushing’s disease or those with de novo disease who were not candidates for surgery.¹

About Isturisa®

Isturisa® is a potent oral inhibitor of 11β-hydroxylase (CYP11B1), the enzyme that catalyses the final step of cortisol biosynthesis in the adrenal gland. Isturisa® is available as 1 mg, 5 mg and 10 mg film-coated tablets. Isturisa®, indicated for the treatment of adult patients with endogenous Cushing’s syndrome, is now available in France as the first EU country to launch. Isturisa® was granted marketing authorization by the European Commission on 9 January 2020. Please see prescribing information for detailed recommendations for the use of this product.⁶

1. Pivonello R et al. Lancet Diabetes Endocrinol 2020; doi: 10.1016/S2213-8587(20)30240-0 [Epub ahead of print]
2. Lacroix A et al. Lancet 2015;386:913–27
3. Nieman LK et al. Am J Med 2005;118:1340–6
4. Pivonello R et al. Lancet Diabetes Endocrinol 2016;4:611–29
5. Nieman LK et al. J Clin Endocrinol Metab 2015;100:2807–31

6. Isturisa® Summary of Product Characteristics, May 2020

About Recordati Rare Diseases

The company’s EMEA headquarters is located in Puteaux, France, with global headquarter offices located in Milan, Italy.

For a full list of products, please click here: www.recordatirarediseases.com/products.

About the Recordati group

Recordati, established in 1926, is an international pharmaceutical group, listed on the Italian Stock Exchange (Reuters RECI.MI, Bloomberg REC IM, ISIN IT 0003828271), with a total staff of more than 4,300, dedicated to the research, development, manufacturing and marketing of pharmaceuticals. Headquartered in Milan, Italy, Recordati has operations throughout the whole of Europe, including Russia, Turkey, North Africa, the United States of America, Canada, Mexico, some South American countries, Japan and Australia. An efficient field force of medical representatives promotes a wide range of innovative pharmaceuticals, both proprietary and under license, in a number of therapeutic areas, including a specialized business dedicated to treatments for rare diseases. Recordati is a partner of choice for new product licenses for its territories. Recordati is committed to the research and development of new specialties with a focus on treatments for rare diseases. Consolidated revenue for 2019 was € 1,481.8 million, operating income was € 465.3 million and net income was € 368.9 million.

For additional information, please visit our websites: www.recordati.com and https://www.recordatirarediseases.com/ or follow us on LinkedIn or Twitter for company updates.

Contacts

Gordon J Daniels

Head of International Marketing

Telephone: +33 (0)607531337

e-mail: [email protected]

Data from the Phase III LINC-3 study, published in Lancet Diabetes & Endocrinology, demonstrate that Isturisa® (osilodrostat) rapidly decreases mean urinary free cortisol (mUFC) in patients with Cushing’s disease.

PUTEAUX, France–(BUSINESS WIRE)–Recordati Rare Diseases announces today that Lancet Diabetes & Endocrinology has published positive results from the Phase III LINC-3 pivotal study of Isturisa®, recently approved for the treatment of endogenous Cushing’s syndrome in adults. Patients with Cushing’s disease, the most common form of endogenous Cushing’s syndrome, have an increased risk of significant comorbidities, including cardiovascular and cerebrovascular diseases as a result of excessive cortisol levels.¹ Data from the large LINC-3 study, which enrolled 137 patients with Cushing’s disease, demonstrate that Isturisa® rapidly reduces mUFC and sustains this reduction alongside improvements in comorbidities, clinical signs and patients’ quality of life over 48 weeks.

“The exciting data, published today, underscore the efficacy and safety of Isturisa® in a prospective setting, and represent a significant advance for the management of patients with Cushing’s disease, a serious and potentially life-threatening rare condition,” said Rosario Pivonello, MD, Professor of Endocrinology at the Federico II University of Naples, Italy. “I would like to thank all the patients who participated in the LINC-3 study, and their families, who have helped to bring this new and welcome treatment option to this underserved patient population.”

The LINC-3 study met its primary endpoint, with significantly more patients maintaining normal mUFC with Isturisa® without a dose increase than placebo (86% vs 29%; P<0.0001) following 8 weeks of randomized withdrawal (week 34). Further analysis of patients’ mUFC response found:

• Over half (53%) of patients achieved the key secondary endpoint of a normal mUFC after an initial 24 weeks of open-label treatment with Isturisa®, without any dose increase after week 12
• Majority (72%) of patients had normal mUFC at week 12, and two-thirds (66%) of patients had normal mUFC at the end of the 48-week study
• Almost all (96%) patients achieved normal mUFC at some point during the study, with a median time to first complete response of 41 days

Decreases in mUFC levels during treatment with Isturisa® were accompanied by improvements in clinical signs and cardiovascular-related risk factors (weight, BMI, blood glucose, blood pressure, and total cholesterol). Isturisa® is well tolerated, with the most common adverse effects in LINC-3 being nausea (42%), headache (34%), fatigue (28%) and adrenal insufficiency (28%).

“The publication of these data in Lancet Diabetes & Endocrinology confirms Isturisa® as an effective new treatment option for patients with Cushing’s syndrome,” said Andrea Recordati, CEO. “Following the recent approval of Isturisa® in the US and EU, we are excited to bring Isturisa® to all of those patients who need it. (Read more…)”

The full manuscript can be accessed online at:

http://www.thelancet.com/journals/landia/article/PIIS2213-8587(20)30240-0/fulltext

About Cushing’s syndrome

Cushing’s syndrome is caused by an inappropriate and chronic exposure to excessive levels of cortisol. The source of this excess of cortisol can be endogenous or exogenous (ie medication).² When the excess cortisol production is triggered by a pituitary adenoma (ie. a tumor of the pituitary gland located in the brain) secreting excess adrenocorticotropic hormone (ACTH), the condition of the patient is defined as Cushing’s disease and comprises about 70% of Cushing’s syndrome cases.^2,3 It is a rare, serious and difficult-to-treat disease that affects approximately one to two patients per million per year. Prolonged exposure to elevated cortisol levels is associated with considerable morbidity, mortality and impaired quality of life as a result of complications and comorbidities.⁴ Normalization of cortisol levels is therefore a primary objective in the treatment of Cushing’s syndrome.⁵

About LINC-3

LINC-3 is a prospective, multicentre, 48-week trial with an 8-week, double-blind, randomized withdrawal phase to evaluate the safety and efficacy of Isturisa® in patients with Cushing’s disease. The primary endpoint in the LINC-3 trial is the proportion of patients randomized to Isturisa® and placebo, separately, at Week 26 with a mUFC ≤ULN at the end of the 8-week randomized withdrawal period (Week 34), without a dose increase during this period. The key secondary endpoint is the proportion of enrolled patients with a mUFC ≤ULN after an initial 24 weeks of open-label treatment with Isturisa® without any dose increase after Week 12. LINC-3 involved 137 patients with persistent or recurrent Cushing’s disease or those with de novo disease who were not candidates for surgery.¹

About Isturisa®

Isturisa® is a potent oral inhibitor of 11β-hydroxylase (CYP11B1), the enzyme that catalyses the final step of cortisol biosynthesis in the adrenal gland. Isturisa® is available as 1 mg, 5 mg and 10 mg film-coated tablets. Isturisa®, indicated for the treatment of adult patients with endogenous Cushing’s syndrome, is now available in France as the first EU country to launch. Isturisa® was granted marketing authorization by the European Commission on 9 January 2020. Please see prescribing information for detailed recommendations for the use of this product.⁶

1. Pivonello R et al. Lancet Diabetes Endocrinol 2020; doi: 10.1016/S2213-8587(20)30240-0 [Epub ahead of print]
2. Lacroix A et al. Lancet 2015;386:913–27
3. Nieman LK et al. Am J Med 2005;118:1340–6
4. Pivonello R et al. Lancet Diabetes Endocrinol 2016;4:611–29
5. Nieman LK et al. J Clin Endocrinol Metab 2015;100:2807–31

6. Isturisa® Summary of Product Characteristics, May 2020

About Recordati Rare Diseases

The company’s EMEA headquarters is located in Puteaux, France, with global headquarter offices located in Milan, Italy.

For a full list of products, please click here: www.recordatirarediseases.com/products.

About the Recordati group

Recordati, established in 1926, is an international pharmaceutical group, listed on the Italian Stock Exchange (Reuters RECI.MI, Bloomberg REC IM, ISIN IT 0003828271), with a total staff of more than 4,300, dedicated to the research, development, manufacturing and marketing of pharmaceuticals. Headquartered in Milan, Italy, Recordati has operations throughout the whole of Europe, including Russia, Turkey, North Africa, the United States of America, Canada, Mexico, some South American countries, Japan and Australia. An efficient field force of medical representatives promotes a wide range of innovative pharmaceuticals, both proprietary and under license, in a number of therapeutic areas, including a specialized business dedicated to treatments for rare diseases. Recordati is a partner of choice for new product licenses for its territories. Recordati is committed to the research and development of new specialties with a focus on treatments for rare diseases. Consolidated revenue for 2019 was € 1,481.8 million, operating income was € 465.3 million and net income was € 368.9 million.

For additional information, please visit our websites: www.recordati.com and https://www.recordatirarediseases.com/ or follow us on LinkedIn or Twitter for company updates.

Contacts

Gordon J Daniels

Head of International Marketing

Telephone: +33 (0)607531337

e-mail: [email protected]

Data from the Phase III LINC-3 study, published in Lancet Diabetes & Endocrinology, demonstrate that Isturisa® (osilodrostat) rapidly decreases mean urinary free cortisol (mUFC) in patients with Cushing’s disease.

PUTEAUX, France–(BUSINESS WIRE)–Recordati Rare Diseases announces today that Lancet Diabetes & Endocrinology has published positive results from the Phase III LINC-3 pivotal study of Isturisa®, recently approved for the treatment of endogenous Cushing’s syndrome in adults. Patients with Cushing’s disease, the most common form of endogenous Cushing’s syndrome, have an increased risk of significant comorbidities, including cardiovascular and cerebrovascular diseases as a result of excessive cortisol levels.¹ Data from the large LINC-3 study, which enrolled 137 patients with Cushing’s disease, demonstrate that Isturisa® rapidly reduces mUFC and sustains this reduction alongside improvements in comorbidities, clinical signs and patients’ quality of life over 48 weeks.

“The exciting data, published today, underscore the efficacy and safety of Isturisa® in a prospective setting, and represent a significant advance for the management of patients with Cushing’s disease, a serious and potentially life-threatening rare condition,” said Rosario Pivonello, MD, Professor of Endocrinology at the Federico II University of Naples, Italy. “I would like to thank all the patients who participated in the LINC-3 study, and their families, who have helped to bring this new and welcome treatment option to this underserved patient population.”

The LINC-3 study met its primary endpoint, with significantly more patients maintaining normal mUFC with Isturisa® without a dose increase than placebo (86% vs 29%; P<0.0001) following 8 weeks of randomized withdrawal (week 34). Further analysis of patients’ mUFC response found:

• Over half (53%) of patients achieved the key secondary endpoint of a normal mUFC after an initial 24 weeks of open-label treatment with Isturisa®, without any dose increase after week 12
• Majority (72%) of patients had normal mUFC at week 12, and two-thirds (66%) of patients had normal mUFC at the end of the 48-week study
• Almost all (96%) patients achieved normal mUFC at some point during the study, with a median time to first complete response of 41 days

Decreases in mUFC levels during treatment with Isturisa® were accompanied by improvements in clinical signs and cardiovascular-related risk factors (weight, BMI, blood glucose, blood pressure, and total cholesterol). Isturisa® is well tolerated, with the most common adverse effects in LINC-3 being nausea (42%), headache (34%), fatigue (28%) and adrenal insufficiency (28%).

“The publication of these data in Lancet Diabetes & Endocrinology confirms Isturisa® as an effective new treatment option for patients with Cushing’s syndrome,” said Andrea Recordati, CEO. “Following the recent approval of Isturisa® in the US and EU, we are excited to bring Isturisa® to all of those patients who need it. (Read more…)”

The full manuscript can be accessed online at:

http://www.thelancet.com/journals/landia/article/PIIS2213-8587(20)30240-0/fulltext

About Cushing’s syndrome

Cushing’s syndrome is caused by an inappropriate and chronic exposure to excessive levels of cortisol. The source of this excess of cortisol can be endogenous or exogenous (ie medication).² When the excess cortisol production is triggered by a pituitary adenoma (ie. a tumor of the pituitary gland located in the brain) secreting excess adrenocorticotropic hormone (ACTH), the condition of the patient is defined as Cushing’s disease and comprises about 70% of Cushing’s syndrome cases.^2,3 It is a rare, serious and difficult-to-treat disease that affects approximately one to two patients per million per year. Prolonged exposure to elevated cortisol levels is associated with considerable morbidity, mortality and impaired quality of life as a result of complications and comorbidities.⁴ Normalization of cortisol levels is therefore a primary objective in the treatment of Cushing’s syndrome.⁵

About LINC-3

LINC-3 is a prospective, multicentre, 48-week trial with an 8-week, double-blind, randomized withdrawal phase to evaluate the safety and efficacy of Isturisa® in patients with Cushing’s disease. The primary endpoint in the LINC-3 trial is the proportion of patients randomized to Isturisa® and placebo, separately, at Week 26 with a mUFC ≤ULN at the end of the 8-week randomized withdrawal period (Week 34), without a dose increase during this period. The key secondary endpoint is the proportion of enrolled patients with a mUFC ≤ULN after an initial 24 weeks of open-label treatment with Isturisa® without any dose increase after Week 12. LINC-3 involved 137 patients with persistent or recurrent Cushing’s disease or those with de novo disease who were not candidates for surgery.¹

About Isturisa®

Isturisa® is a potent oral inhibitor of 11β-hydroxylase (CYP11B1), the enzyme that catalyses the final step of cortisol biosynthesis in the adrenal gland. Isturisa® is available as 1 mg, 5 mg and 10 mg film-coated tablets. Isturisa®, indicated for the treatment of adult patients with endogenous Cushing’s syndrome, is now available in France as the first EU country to launch. Isturisa® was granted marketing authorization by the European Commission on 9 January 2020. Please see prescribing information for detailed recommendations for the use of this product.⁶

1. Pivonello R et al. Lancet Diabetes Endocrinol 2020; doi: 10.1016/S2213-8587(20)30240-0 [Epub ahead of print]
2. Lacroix A et al. Lancet 2015;386:913–27
3. Nieman LK et al. Am J Med 2005;118:1340–6
4. Pivonello R et al. Lancet Diabetes Endocrinol 2016;4:611–29
5. Nieman LK et al. J Clin Endocrinol Metab 2015;100:2807–31

6. Isturisa® Summary of Product Characteristics, May 2020

About Recordati Rare Diseases

The company’s EMEA headquarters is located in Puteaux, France, with global headquarter offices located in Milan, Italy.

For a full list of products, please click here: www.recordatirarediseases.com/products.

About the Recordati group

Recordati, established in 1926, is an international pharmaceutical group, listed on the Italian Stock Exchange (Reuters RECI.MI, Bloomberg REC IM, ISIN IT 0003828271), with a total staff of more than 4,300, dedicated to the research, development, manufacturing and marketing of pharmaceuticals. Headquartered in Milan, Italy, Recordati has operations throughout the whole of Europe, including Russia, Turkey, North Africa, the United States of America, Canada, Mexico, some South American countries, Japan and Australia. An efficient field force of medical representatives promotes a wide range of innovative pharmaceuticals, both proprietary and under license, in a number of therapeutic areas, including a specialized business dedicated to treatments for rare diseases. Recordati is a partner of choice for new product licenses for its territories. Recordati is committed to the research and development of new specialties with a focus on treatments for rare diseases. Consolidated revenue for 2019 was € 1,481.8 million, operating income was € 465.3 million and net income was € 368.9 million.

For additional information, please visit our websites: www.recordati.com and https://www.recordatirarediseases.com/ or follow us on LinkedIn or Twitter for company updates.

Contacts

Gordon J Daniels

Head of International Marketing

Telephone: +33 (0)607531337

e-mail: [email protected]