Mucormycosis

Designation follows December 2023 FDA approval for the treatment of these serious, potentially life-threatening fungal infections in children CRESEMBA receives seven years and six months of US market exclusivity for these pediatric indications NORTHBROOK, Ill., March 11, 2024 /PRNewswire/ -- Astellas Pharma US, Inc. (TSE: 4503, President: Mark Reisenauer, "Astellas") announced today that the U.S. Food and Drug Administration (FDA) has granted orphan drug and pediatric exclusivity to CRESEMBA® (isavuconazonium sulfate) for the treatment of invasive aspergillosis (IA) and invasive mucormycosis (IM) in pediatric patients. On December 8, 2023, CRESEMBA for injection was approved for pediatric patients 1 year of age and older and capsules for pediatric patients 6 years of age and older who weigh 16 kilograms (kg) and greater. 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 Dec. 8, 2023. Pediatric exclusivity extends that period by another six months. The FDA previously granted orphan drug exclusivity for CRESEMBA in 2015 for the treatment of IA and IM in adults. Laura Kovanda, PhD, Executive Director, Asset Lead, BioPharma Development, Astellas "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 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 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. For Full Prescribing Information, please visit here. About Astellas Pharma US Astellas Pharma US, Inc. is a U.S. affiliate of Tokyo-based Astellas Pharma Inc., a pharmaceutical company 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. CRESEMBA was licensed from and co-developed with Basilea Pharmaceutica International Ltd, Allschwil. For more information on Astellas, please visit: . You can also follow us on Twitter at @AstellasUS, Facebook at or LinkedIn at . 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 . 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 Mar 6. PMID: 20359458. 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 SOURCE Astellas Pharma US, Inc.

Cresemba is approved as an injection and capsule for the treatment of pediatric invasive aspergillosis and invasive mucormycosis. Image credit: JHVEPhoto/Shutterstock.com Following approval for the antifungal therapy from the US Food and Drug Administration (FDA) in December 2023, Astellas’ Cresemba (isavuconazonium sulfate) has gained FDA orphan drug exclusivity and pediatric market exclusivity for the treatment of invasive aspergillosis (IA) and invasive mucormycosis (IM). Cresemba being the first FDA-approved medication for the treatment of IA and IM, Astellas has gained orphan drug exclusivity that grants the drug seven years of US market exclusivity in its approved indication. The auxiliary pediatric exclusivity gives Cresemba an additional six months of protection, as per the 11 March press announcement. On 8 December 2023, the injectable Cresemba was awarded FDA approval as a treatment for IA and IM patients aged one or older.  A separate capsule formulation of the drug is indicated to treat patients ages six and older, weighing at least 16kg. The consensus from GlobalData, the parent company of Pharmaceutical Technology , forecasts predict that Cresemba will generate $450m in 2023. The FDA approval was granted based on data from two paediatric clinical studies, one of which was a Phase II trial (NCT03816176) evaluating patients aged between one to 17 years. The non-randomised, open-label, single-group assignment Phase II study assessed drug efficacy, safety and pharmacokinetics in 31 paediatric patients. See Also: Mesoblast eyes accelerated approval filing for heart failure cell therapy Supernus Pharmaceuticals files patent for modified release formulation of viloxazine with high-drug load As per the Centers for Disease Control and Prevention (CDC), IA occurs predominantly in immunocompromised populations when the aspergillus fungus gives rise to serious infections. IM is a rare fungal infection caused by environmental moulds called mucormycetes. “Astellas recognises the importance of addressing significant unmet medical needs, especially for pediatric patients with rare and potentially life-threatening IA and IM infections,” said Laura Kovanda, PhD, executive director at Astellas.

Allschwil, Switzerland, March 11, 2024 Basilea Pharmaceutica Ltd, Allschwil (SIX: BSLN), a commercial-stage biopharmaceutical company committed to meeting the needs of patients with severe bacterial and fungal infections, announced today that the continued strong sales performance of the antifungal Cresemba® (isavuconazole) by its license partner Pfizer Inc. in the Asia Pacific region and China exceeded the sales threshold triggering a USD 1.25 million milestone payment. David Veitch, Basilea’s Chief Executive Officer, stated: “This further milestone payment for Asia Pacific and China reflects the significant medical need and strong growth momentum of Cresemba in this region. We are pleased to see that Cresemba continues to serve a medical need in patients suffering from life-threatening invasive mold infections.” The license agreement between Basilea and Pfizer for Cresemba covers Europe (excluding the Nordic countries) as well as 16 countries in the Asia Pacific region and China. Cresemba is approved and marketed in more than 70 countries, including the United States, most EU member states and additional countries inside and outside of Europe. According to the latest available market data, total global in-market sales of Cresemba in the twelve months between October 2022 and September 2023 amounted to USD 445 million, a 22 percent growth year-on-year.1 About Isavuconazole (Cresemba®) Isavuconazole is an intravenous (i.v.) and oral azole antifungal, commercialized under the trade name Cresemba®. Basilea has entered into several license and distribution agreements for isavuconazole covering approximately 115 countries. In the 27 European Union member states, as well as in Iceland, Liechtenstein, Norway and the U.K., isavuconazole is approved for the treatment of adult patients with invasive aspergillosis and for adult patients with mucormycosis for whom amphotericin B is inappropriate.2 In China, the oral and intravenous formulations are approved for the treatment of adult patients with invasive aspergillosis and invasive mucormycosis. Isavuconazole is also approved in the United States and several additional countries in Europe and beyond, including Japan.3 It has orphan drug designation in the US, Europe and Australia for its approved indications. About Basilea Basilea is a commercial-stage biopharmaceutical company founded in 2000 and headquartered in Switzerland. We are committed to discovering, developing and commercializing innovative drugs to meet the needs of patients with severe bacterial or fungal infections. We have successfully launched two hospital brands, Cresemba for the treatment of invasive fungal infections and Zevtera for the treatment of bacterial infections. In addition, we have preclinical and clinical anti-infective assets in our portfolio. Basilea is listed on the SIX Swiss Exchange (SIX: BSLN). Please visit basilea.com. Disclaimer This communication expressly or implicitly contains certain forward-looking statements, such as "believe", "assume", "expect", "forecast", "project", "may", "could", "might", "will" or similar expressions concerning Basilea Pharmaceutica Ltd, Allschwil and its business, including with respect to the progress, timing and completion of research, development and clinical studies for product candidates. Such statements involve certain known and unknown risks, uncertainties and other factors, which could cause the actual results, financial condition, performance or achievements of Basilea Pharmaceutica Ltd, Allschwil to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statements. Basilea Pharmaceutica Ltd, Allschwil is providing this communication as of this date and does not undertake to update any forward-looking statements contained herein as a result of new information, future events or otherwise. For further information, please contact: Peer Nils Schröder, PhD Head of Corporate Communications & Investor Relations Basilea Pharmaceutica Ltd, Allschwil Hegenheimermattweg 167b 4123 Allschwil Switzerland Phone +41 61 606 1102 E-mail media_relations@basilea.com investor_relations@basilea.com This press release can be downloaded from . References IQVIA Analytics Link, September 2023. In-market sales reported as moving annual total (MAT) in U.S. dollar. European Public Assessment Report (EPAR) Cresemba: [Accessed: March 08, 2024] The registration status and approved indications may vary from country to country. Attachment Press release (PDF)