FDA Grants Orphan Drug and Pediatric Exclusivities for CRESEMBA® (isavuconazonium sulfate) for Invasive Aspergillosis and Invasive Mucormycosis in Children
Designation follows
CRESEMBA receives seven years and six months of US market exclusivity for these pediatric indications
The FDA grants orphan drug exclusivity to orphan drugs that receive FDA marketing approval. As the first company to obtain FDA approval for the treatment of IA and IM in patients as young as one for a triazole antifungal, Astellas has received orphan drug exclusivity, which provides seven years of exclusive marketing rights for CRESEMBA in those indications beginning from the date of approval of the supplemental New Drug Application on
"Astellas recognizes the importance of addressing significant unmet medical needs, especially for pediatric patients with rare and potentially life-threatening IA and IM infections. I am incredibly proud of the Astellas team for advancing research, development and commercialization to offer CRESEMBA to pediatric patients who have limited treatment options."
CRESEMBA is the only azole antifungal therapy FDA approved for the treatment of IA and IM in patients as young as one.
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.1 Invasive mucormycosis is a rare and often life-threatening fungal infection.2 IA and IM are a major cause of morbidity and death among immunocompromised and hospitalized pediatric patients.3
About CRESEMBA® (isavuconazonium sulfate)
CRESEMBA® (isavuconazonium sulfate) is an azole antifungal indicated for the treatment of invasive aspergillosis and invasive mucormycosis as follows:
- CRESEMBA for injection: adults and pediatric patients 1 year of age and older
- CRESEMBA capsules: adults and pediatric patients 6 years of age and older who weigh 16 kg and greater
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
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
In adult patients, 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%).
In adult patients, 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%).
In pediatric patients, the most frequently reported adverse reactions were diarrhea (26%), abdominal pain (23%), vomiting (21%), elevated liver chemistry tests (18%), rash (14%), nausea (13%), pruritus (13%), and headache (12%).
In general, adverse reactions in pediatric patients (including serious adverse reactions and adverse reactions leading to permanent discontinuation of CRESEMBA) were similar to those reported in adults.
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About Astellas
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.
1 Thornton CR. Detection of invasive aspergillosis. Adv Appl Microbiol. 2010;70:187-216. doi: 10.1016/S0065-2164(10)70006-X. Epub 2010
2 Zhang Y, Sung AH, Rubinstein E, Benigno M, Chambers R, Patino N, Aram JA. Characterizing patients with rare mucormycosis infections using real-world data. BMC Infect Dis. 2022;22(1):154. doi: 10.1186/s12879-022-07115-w. PMID: 35164701; PMCID: PMC8845356.
3 Pana ZD, Roilides E, Warris A, Groll AH, Zaoutis T. Epidemiology of Invasive Fungal Disease in Children. J Pediatric Infect Dis Soc. 2017;6(suppl_1):S3-S11. doi:10.1093/jpids/pix046
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