CHICAGO--(BUSINESS WIRE)--Xeris Biopharma Holdings, Inc. (Nasdaq: XERS), a biopharmaceutical company developing and commercializing unique therapies for patient populations in endocrinology, neurology, and gastroenterology, today announced that Recorlev® (levoketoconazole) is now available for prescription. The U.S. Food and Drug Administration (FDA) approved Recorlev on December 31, 2021 for the treatment of endogenous hypercortisolemia in adult patients with Cushing’s syndrome for whom surgery is not an option or has not been curative.1
“The commercial availability of Recorlev represents a significant milestone for the Cushing’s syndrome community, particularly for people living with uncontrolled disease, who until now were faced with limited therapeutic options,” said Paul R. Edick, Chairman and CEO of Xeris Biopharma. “Xeris is proud to introduce this meaningful new treatment option to patients in the U.S. and is focused on meeting the needs of the rare disease community by ensuring access to treatment and providing comprehensive patient and physician support services.”
Xeris has also partnered with PANTHERx Rare Specialty Pharmacy to provide a customized support and product distribution program, Xeris CareConnection™, for members of the Recorlev ecosystem, including patients, caregivers, physicians, and payors. Xeris CareConnection provides access to pharmacists, case managers and access managers, including white-glove services throughout the entire treatment journey. Patients will also receive welcome information, therapy onboarding, at-home delivery of medication, a discreet courier service for urinary free cortisol (UFC) test collection, automatic monthly refill shipments, financial assistance, one-on-one support, and ongoing educational resources. Xeris CareConnection also supports healthcare professionals and their teams through education on access and reimbursement. To get started with Recorlev, reach out to Xeris CareConnection (available Monday–Friday, 8 a.m.–7 p.m. ET) at 1-844-444-RCLV (7258).
“Endogenous Cushing’s syndrome (CS), a rare and potentially fatal endocrine disease caused by chronic, elevated cortisol exposure, affects women three times more often than men,” said Ken Johnson, Pharm.D., SVP, Global Development and Medical Affairs at Xeris. “Normalization of cortisol levels is the first and most important clinical objective in the treatment of Cushing’s syndrome and the approval of new medicines like Recorlev can aid physicians and patients to achieve this objective. Many of the symptoms of CS can significantly impact self-esteem, body image, and intimate relationships, therefore, it is exciting to now be able to offer patients suffering from this condition an effective oral treatment option.”
Xeris is committed to ensuring that everyone who needs access to their therapies will receive it. Consequently, Xeris has established a $0 co-pay program and Patient Assistance Program for eligible patients with financial hardship or limited or no insurance. For more information, please visit www.RECORLEV.com.
The FDA approval of Recorlev® was based upon safety and efficacy data from two positive Phase 3 studies that evaluated a combined study population of 166 patients, which was representative of the adult drug-treated U.S. population with Cushing’s syndrome.1 LOGICS, a double-blind, placebo-controlled randomized-withdrawal study met its key endpoint of normalizing and maintaining therapeutic response compared with placebo (detailed results here).1 The supportive SONICS study met its primary and key secondary endpoints, significantly reducing and normalizing mean urinary free cortisol concentrations without a dose increase (detailed results here).1,2
About Cushing’s Syndrome
Endogenous Cushing’s syndrome is a rare, serious, and potentially fatal endocrine disease caused by chronic elevated cortisol exposure—often the result of a benign tumor of the pituitary gland. This benign tumor tells the body to overproduce high levels of cortisol for a sustained period of time, which often results in characteristic physical signs and symptoms that are distressing to patients. The disease is most common among adults between the ages of 30–50, and it affects women three times more often than men. Women with Cushing's syndrome may experience a variety of health issues including menstrual problems, difficulty becoming pregnant, excess male hormones (androgens), primarily testosterone, which can cause hirsutism (growth of coarse body hair in a male pattern), oily skin, and acne.3
Additionally, the multisystem complications of the disease are potentially life threatening. These include metabolic changes such as high blood sugar or diabetes, high blood pressure, high cholesterol, fragility of various tissues including blood vessels, skin, muscle, and bone, and psychological disturbances such as depression, anxiety, and insomnia.3 Untreated, the five-year survival rate is only approximately 50%.4
Recorlev® (levoketoconazole) is a cortisol synthesis inhibitor for the treatment of endogenous hypercortisolemia in adult patients with Cushing’s syndrome for whom surgery is not an option or has not been curative.1 Endogenous Cushing’s syndrome is a rare but serious and potentially fatal endocrine disease caused by chronic elevated cortisol exposure.2 Recorlev is the pure 2S,4R enantiomer of ketoconazole, a steroidogenesis inhibitor.1 Recorlev has demonstrated in two successful Phase 3 studies to significantly reduce mean urinary free cortisol.1
The Phase 3 program for Recorlev included LOGICS and SONICS, two multinational studies designed to evaluate the safety and efficacy of Recorlev when used to treat endogenous Cushing’s syndrome. LOGICS, a double-blind, placebo-controlled randomized-withdrawal study met its key endpoint of normalizing and maintaining therapeutic response compared with placebo (detailed results here).1 The supportive SONICS study met its primary and secondary endpoints, significantly reducing and normalizing mean urinary free cortisol concentrations without a dose increase.1,2 The ongoing open-label OPTICS study will gather further useful information related to the long-term use of Recorlev.
Recorlev received orphan drug designation from the FDA and the European Medicines Agency for the treatment of endogenous Cushing's syndrome.
Indication & Important Safety Information for Recorlev®
BOXED WARNING: HEPATOTOXICITY AND QT PROLONGATION
Cases of hepatotoxicity with fatal outcome or requiring liver transplantation have been reported with oral ketoconazole. Some patients had no obvious risk factors for liver disease. Recorlev is associated with serious hepatotoxicity. Evaluate liver enzymes prior to and during treatment.
Recorlev is associated with dose-related QT interval prolongation. QT interval prolongation may result in life-threatening ventricular dysrhythmias such as torsades de pointes. Perform ECG and correct hypokalemia and hypomagnesemia prior to and during treatment.
Recorlev is a cortisol synthesis inhibitor indicated for the treatment of endogenous hypercortisolemia in adult patients with Cushing’s syndrome for whom surgery is not an option or has not been curative.
Limitations of Use
Recorlev is not approved for the treatment of fungal infections.
- Cirrhosis, acute liver disease or poorly controlled chronic liver disease, baseline AST or ALT > 3 times the upper limit of normal, recurrent symptomatic cholelithiasis, a prior history of drug induced liver injury due to ketoconazole or any azole antifungal therapy that required discontinuation of treatment, or extensive metastatic liver disease.
- Taking drugs that cause QT prolongation associated with ventricular arrhythmias, including torsades de pointes.
- Prolonged QTcF interval > 470 msec at baseline, history of torsades de pointes, ventricular tachycardia, ventricular fibrillation, or prolonged QT syndrome.
- Known hypersensitivity to levoketoconazole, ketoconazole or any excipient in Recorlev.
- Taking certain drugs that are sensitive substrates of CYP3A4 or CYP3A4 and P-gp.
WARNINGS AND PRECAUTIONS
Serious hepatotoxicity has been reported in patients receiving Recorlev, irrespective of the dosages used or the treatment duration. Drug-induced liver injury (peak ALT or AST greater than 3 times upper limit of normal) occurred in patients using Recorlev. Avoid concomitant use of Recorlev with hepatotoxic drugs. Advise patient to avoid excessive alcohol consumption while on treatment with Recorlev. Routinely monitor liver enzymes and bilirubin during treatment.
Use Recorlev with caution in patients with other risk factors for QT prolongation, such as congestive heart failure, bradyarrhythmias, and uncorrected electrolyte abnormalities, with more frequent ECG monitoring considered. Routinely monitor ECG and blood potassium and magnesium levels during treatment.
Recorlev lowers cortisol levels and may lead to hypocortisolism with a potential for life-threatening adrenal insufficiency. Lowering of cortisol levels can cause nausea, vomiting, fatigue, abdominal pain, loss of appetite, and dizziness. Significant lowering of serum cortisol levels may result in adrenal insufficiency that can be manifested by hypotension, abnormal electrolyte levels, and hypoglycemia. Routinely monitor 24-hour urine free cortisol, morning serum or plasma cortisol, and patient’s signs and symptoms for hypocortisolism during treatment.
Hypersensitivity to Recorlev has been reported. Anaphylaxis and other hypersensitivity reactions including urticaria have been reported with oral ketoconazole.
Risks Related to Decreased Testosterone
Recorlev may lower serum testosterone in men and women. Potential clinical manifestations of decreased testosterone concentrations in men may include gynecomastia, impotence, and oligospermia. Potential clinical manifestations of decreased testosterone concentrations in women include decreased libido and mood changes.
Most common adverse reactions (incidence > 20%) are nausea/vomiting, hypokalemia, hemorrhage/contusion, systemic hypertension, headache, hepatic injury, abnormal uterine bleeding, erythema, fatigue, abdominal pain/dyspepsia, arthritis, upper respiratory infection, myalgia, arrhythmia, back pain, insomnia/sleep disturbances, and peripheral edema.
- Consult approved product labeling for drugs that are substrates of CYP3A4, P-gp, OCT2, and MATE prior to initiating Recorlev.
- Sensitive CYP3A4 or CYP3A4 and P-gp Substrates: Concomitant use of Recorlev with these substrates is contraindicated or not recommended.
- Atorvastatin: Use lowest atorvastatin dose possible and monitor for adverse reactions for dosages exceeding 20 mg daily.
- Metformin: Monitor glycemia, kidney function, and vitamin B12 and adjust metformin dosage as needed.
- Strong CYP3A4 Inhibitors or Inducers: Avoid use of these drugs 2 weeks before and during Recorlev treatment.
- Gastric Acid Modulators: See Full Prescribing Information for recommendations regarding concomitant use with Recorlev.
USE IN SPECIFIC POPULATIONS
Lactation: Advise not to breastfeed during treatment and for one day after final dose.
To report SUSPECTED ADVERSE REACTIONS, contact Xeris Pharmaceuticals, Inc. at 1-877-937-4737 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Please see Full Prescribing Information, including Boxed Warning.
About Xeris Biopharma
Xeris (Nasdaq: XERS) is a biopharmaceutical company developing and commercializing unique therapies for patient populations in endocrinology, neurology, and gastroenterology. Xeris has three commercially available products; Gvoke®, a ready-to-use liquid glucagon for the treatment of severe hypoglycemia, Keveyis®, the first and only FDA-approved therapy for primary periodic paralysis, and Recorlev® for the treatment of endogenous Cushing’s syndrome. Xeris also has a robust pipeline of development programs to extend the current marketed products into important new indications and uses and bring new products forward using its proprietary formulation technology platforms, XeriSol™ and XeriJect™, supporting long-term product development and commercial success.
Any statements in this press release about future expectations, plans and prospects for Xeris Biopharma Holdings, Inc. including statements regarding the market and therapeutic potential of its products and product candidates, expectations regarding the timing of the commercial launch of Recorlev, estimates and projections about the potential benefits of the Strongbridge Biopharma acquisition, the future performance of the combined company and estimated synergies, the timing or likelihood of expansion into additional markets and other statements containing the words “will,” “would,” “continue,” and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. These forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, reliance on third-party suppliers for Gvoke®, Ogluo®, Keveyis®, and Recorlev® the regulatory approval of its product candidates, its ability to market and sell its products, failure to realize the expected benefits of the acquisition, failure to promptly and effectively integrate Strongbridge’s businesses, general economic and business conditions that affect the combined company following the consummation of the acquisition, the impact of the COVID-19 pandemic on the combined company following the consummation of the transaction, changes in global, political, economic, business, competitive, market and regulatory forces, future exchange and interest rates, changes in tax laws, regulations, rates and policies, future business acquisitions or disposals and competitive developments and the other risks described in our Quarterly Report on Form 10-Q and other reports we file from time to time with the SEC. These forward-looking statements are based on numerous assumptions and assessments made in light of Xeris’ experience and perception of historical trends, current conditions, business strategies, operating environment, future developments, and other factors it believes appropriate. By their nature, forward-looking statements involve known and unknown risks and uncertainties because they relate to events and depend on circumstances that will occur in the future. The factors described in the context of such forward-looking statements in this communication could cause Xeris’ plans with respect to Strongbridge, Xeris’ plans with respect to its products and product candidates, Xeris’ actual results, performance or achievements, industry results and developments to differ materially from those expressed in or implied by such forward-looking statements. Although it is believed that the expectations reflected in such forward-looking statements are reasonable, no assurance can be given that such expectations will prove to have been correct and persons reading this communication are therefore cautioned not to place undue reliance on these forward-looking statements which speak only as at the date of this communication. Additional information about economic, competitive, governmental, technological, and other factors that may affect Xeris is set forth in Item 1A, “Risk Factors,” in Xeris’ 2020 Annual Report on Form 10-K, which has been filed with the SEC and other important factors in Xeris’ subsequent filings with the SEC, the contents of which are not incorporated by reference into, nor do they form part of, this communication. Additional information about economic, competitive, governmental, technological, and other factors that may affect Strongbridge is set forth in Item 1A, “Risk Factors,” in Strongbridge’s 2020 Annual Report on Form 10-K, which has been filed with the SEC, the contents of which are not incorporated by reference into, nor do they form part of, this communication. Any forward-looking statements in this communication are based upon information available to Xeris, as of the date of this communication and, while believed to be true when made, may ultimately prove to be incorrect. Subject to any obligations under applicable law, Xeris does not undertake any obligation to update any forward-looking statement whether as a result of new information, future developments or otherwise, or to conform any forward-looking statement to actual results, future events, or to changes in expectations. All subsequent written and oral forward-looking statements attributable to Xeris or any person acting on behalf of any of them are expressly qualified in their entirety by this paragraph.
1. Recorlev [prescribing information]. Chicago, IL: Xeris Pharmaceuticals, Inc.; 2021. 2. Fleseriu M, et al. Lancet Diabetes Endocrinol. 2019;7(11):855-865. 3. Pivonello R et al. Lancet Diabetes Endocrinol. 2016; 4: 611-29. 4. Plotz CM, et al. Am J Med. 1952 November;13(5):597-614.
Recorlev®, Xeris Pharmaceuticals®, Xeris CareConnectionTM, Keveyis®, Gvoke®, and Ogluo® are trademarks owned by or licensed to Xeris Pharmaceuticals, Inc. PANTHERx Rare Pharmacy is a service mark of PANTHERx Rare, LLC. All other trademarks referenced herein are the property of their respective owners. All rights reserved. US-PR-22-00001 1/22