U.S. FDA Accepts Astellas' sNDA for CRESEMBA® (isavuconazonium sulfate) in Children

If approved, CRESEMBA will offer a new treatment option for pediatric patients facing certain invasive fungal infections

NORTHBROOK, Ill., Aug. 10, 2023 /PRNewswire/ -- Astellas Pharma US, Inc. (President: Mark Reisenauer, "Astellas") announced that the U.S. Food and Drug Administration (FDA) has accepted the company's supplemental New Drug Application (sNDA) for CRESEMBA^® (isavuconazonium sulfate), a prodrug of isavuconazole, an azole antifungal drug, seeking approval for the treatment of invasive aspergillosis (IA) or invasive mucormycosis (IM) in pediatric patients aged one to 17 years old. Under the Prescription Drug User Fee Act (PDUFA), the FDA has set a target action date of December 9, 2023.

CRESEMBA is already approved by the FDA for the treatment of IA and IM in adults. If approved for pediatric use, it may offer children significant advances in treatment or may provide a treatment where no adequate therapy exists. IA and IM are a major cause of morbidity and death among immunocompromised and hospitalized pediatric patients.¹

"While rare in the general population, invasive aspergillosis or invasive mucormycosis can be incredibly dangerous for immunocompromised children, including those faced with blood and other cancers, and there are very limited treatment options," said Tadaaki Taniguchi, MD, PhD, chief medical officer, Astellas. "The collective efforts by our research and development teams, which have led to the successful sNDA acceptance for CRESEMBA by the FDA, reflect our ongoing commitment to addressing vulnerable populations with high unmet medical needs."

"Since its approval over eight years ago, CRESEMBA has been helping adult patients and their physicians fight certain life-threatening fungal infections when they are often critically ill with other diseases," said Lynn Fenicchia, senior vice president and Head of U.S. Medical Specialties Business Unit, Astellas. "This sNDA acceptance by the FDA brings Astellas one step closer to helping pediatric patients by potentially having a new treatment option available for IA and IM for a younger patient population, if approved."

The sNDA is based on results from a Phase 2 open-label, non-comparative, multicenter study (NCT03816176), evaluating the safety, efficacy and pharmacokinetics of CRESEMBA for the treatment of IA or IM in pediatric patients aged one to 17 years old. Detailed results will be presented at a future medical meeting.

About Invasive Aspergillosis and Invasive Mucormycosis
Invasive aspergillosis can be a life-threatening fungal infection that is seen predominantly in immunocompromised patients, such as patients with leukemia.² Invasive mucormycosis is a rare and often life-threatening fungal infection, for which clinical and epidemiological understanding is lacking.³ Both IA and IM are known for high morbidity and mortality.^2,3

About CRESEMBA^® (isavuconazonium sulfate)  
CRESEMBA^® (isavuconazonium sulfate) is a prodrug of isavuconazole, an azole antifungal drug. CRESEMBA is indicated for patients 18 years of age and older for the treatment of invasive aspergillosis and invasive mucormycosis.⁴

Specimens for fungal culture and other relevant laboratory studies (including histopathology) to isolate and identify causative organism(s) should be obtained prior to initiating antifungal therapy. Therapy may be instituted before the results of the cultures and other laboratory studies are known. However, once these results become available, antifungal therapy should be adjusted accordingly.

Important Safety Information for CRESEMBA (isavuconazonium sulfate)

Contraindications

• CRESEMBA is contraindicated in persons with known hypersensitivity to isavuconazole
• Coadministration of strong CYP3A4 inhibitors, such as ketoconazole or high-dose ritonavir (400 mg every 12 hours), with CRESEMBA is contraindicated because strong CYP3A4 inhibitors can significantly increase the plasma concentration of isavuconazole
• Coadministration of strong CYP3A4 inducers, such as rifampin, carbamazepine, St. John's wort, or long-acting barbiturates with CRESEMBA is contraindicated because strong CYP3A4 inducers can significantly decrease the plasma concentration of isavuconazole
• CRESEMBA shortened the QTc interval in a concentration-related manner. CRESEMBA is contraindicated in patients with familial short QT syndrome

Warnings and Precautions

Hepatic Adverse Drug Reactions (e.g., elevations in ALT, AST, alkaline phosphatase, total bilirubin) have been reported in clinical trials and were generally reversible and did not require discontinuation of CRESEMBA. Cases of severe hepatic adverse drug reactions including hepatitis, cholestasis or hepatic failure including death have been reported in patients with serious underlying medical conditions (e.g., hematologic malignancy) during treatment with azole antifungal agents, including CRESEMBA. Evaluate liver tests at the start and during therapy. Monitor patients who develop liver abnormalities during CRESEMBA therapy for severe hepatic injury. Discontinue if clinical signs and symptoms consistent with liver disease develop that may be attributable to CRESEMBA.

Infusion-Related Reactions including hypotension, dyspnea, chills, dizziness, paresthesia, and hypoesthesia were reported during intravenous administration of CRESEMBA. Discontinue the infusion if these reactions occur.

Hypersensitivity Reactions: Anaphylactic reactions, with fatal outcome, have been reported during treatment with CRESEMBA. Serious skin reactions, such as Stevens Johnson syndrome, have been reported during treatment with other azole antifungal agents. Discontinue CRESEMBA if anaphylactic or serious skin reactions occur, and initiate supportive treatment as needed.

Embryo-Fetal Toxicity: During pregnancy, CRESEMBA may cause fetal harm when administered, and CRESEMBA should only be used if the potential benefit to the patient outweighs the risk to the fetus. Women who become pregnant while receiving CRESEMBA are encouraged to contact their physician.

Drug Interactions: Coadministration of CRESEMBA with strong CYP3A4 inhibitors such as ketoconazole or high-dose ritonavir and strong CYP3A4 inducers such as rifampin, carbamazepine, St. John's Wort, or long-acting barbiturates is contraindicated.

Drug Particulates: Following dilution, CRESEMBA intravenous formulation may form precipitate from the insoluble isavuconazole. Administer CRESEMBA through an in-line filter.

Adverse Reactions

The most frequently reported adverse reactions among CRESEMBA-treated patients were nausea (26%), vomiting (25%), diarrhea (22%), headache (17%), elevated liver chemistry tests (16%), hypokalemia (14%), constipation (13%), dyspnea (12%), cough (12%), peripheral edema (11%), and back pain (10%).

The adverse reactions which most often led to permanent discontinuation of CRESEMBA therapy during the clinical trials were: confusional state (0.7%), acute renal failure (0.7%), increased blood bilirubin (0.5%), convulsion (0.5%), dyspnea (0.5%), epilepsy (0.5%), respiratory failure (0.5%), and vomiting (0.5%).

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About Astellas Pharma US
Astellas Pharma US, Inc. is a U.S. affiliate of Tokyo-based Astellas Pharma Inc., a pharmaceutical conducting business in more than 70 countries around the world. Astellas stands on the forefront of healthcare change to turn innovative science into value for patients. Keeping our focus on addressing unmet medical needs and conducting our business with ethics and integrity enables us to improve the health of people throughout the U.S. and around the world. For more information on Astellas, please visit: https://www.astellas.com/us. You can also follow us on Twitter at @AstellasUS, Facebook at www.facebook.com/AstellasUS or LinkedIn at www.linkedin.com/company/astellas-pharma-us.

About Astellas
Astellas Pharma Inc. is a pharmaceutical company conducting business in more than 70 countries around the world. We are promoting the Focus Area Approach that is designed to identify opportunities for the continuous creation of new drugs to address diseases with high unmet medical needs by focusing on Biology and Modality. Furthermore, we are also looking beyond our foundational Rx focus to create Rx+^® healthcare solutions that combine our expertise and knowledge with cutting-edge technology in different fields of external partners. Through these efforts, Astellas stands on the forefront of healthcare change to turn innovative science into VALUE for patients. For more information, please visit our website at https://www.astellas.com/en.

Cautionary Notes
In this press release, statements made with respect to current plans, estimates, strategies and beliefs and other statements that are not historical facts are forward-looking statements about the future performance of Astellas. These statements are based on management's current assumptions and beliefs in light of the information currently available to it and involve known and unknown risks and uncertainties. A number of factors could cause actual results to differ materially from those discussed in the forward-looking statements. Such factors include, but are not limited to: (i) changes in general economic conditions and in laws and regulations, relating to pharmaceutical markets, (ii) currency exchange rate fluctuations, (iii) delays in new product launches, (iv) the inability of Astellas to market existing and new products effectively, (v) the inability of Astellas to continue to effectively research and develop products accepted by customers in highly competitive markets, and (vi) infringements of Astellas' intellectual property rights by third parties.

The safety and efficacy of the agents discussed herein are under investigation and have not been established. There is no guarantee that the agents will receive regulatory approval and become commercially available for uses being investigated. Information about pharmaceutical products (including products currently in development) which is included in this press release is not intended to constitute an advertisement or medical advice.

SOURCE Astellas Pharma US, Inc.