OSAKA, Japan & CAMBRIDGE, Mass.--(BUSINESS WIRE)--Takeda (TSE:4502/NYSE:TAK) today announced that the U.S. Food and Drug Administration (FDA) has approved EOHILIA (budesonide oral suspension), the first and only FDA-approved oral therapy for people 11 years and older with eosinophilic esophagitis (EoE).¹ It will be available in 2 mg/10 mL convenient, single-dose stick packs by the end of February.

EOHILIA is a corticosteroid indicated for 12 weeks of treatment in patients 11 years and older with EoE.¹ Developed specifically for EoE, EOHILIA’s novel formulation of budesonide confers thixotropic properties – flowing more freely when shaken and returning to a more viscous state when swallowed.^1,2

“Various formulations of corticosteroids have been used in the past to manage EoE, but in an off-label capacity and using multiple delivery options. With EOHILIA, it’s gratifying to now have an FDA-approved treatment specifically formulated for a consistent dose delivery with demonstrated ability to address esophageal inflammation and EoE dysphagia symptoms,” said Ikuo Hirano, MD, professor of medicine and director of the Kenneth C. Griffin Esophageal Center in the Division of Gastroenterology and Hepatology at Northwestern University Feinberg School of Medicine. “As the treatment needs and goals of patients with EoE can vary, I welcome the flexibility that EOHILIA offers as an oral medication.”

The FDA approval of EOHILIA 2 mg twice daily is based on efficacy and safety data from two multicenter, randomized, double-blind, parallel-group, placebo-controlled 12-week studies (Study 1 and Study 2) in patients (ages 11 to 56 and 11 to 42, respectively) with EoE.¹ In both studies, patients received at least one dose of either EOHILIA 2 mg twice daily or placebo orally twice daily. Efficacy endpoints included histologic remission (peak eosinophil count of ≤6 per high-powered field across all available esophageal levels) and the absolute change from baseline in patient-reported Dysphagia Symptom Questionnaire (DSQ) combined score after 12 weeks of treatment. The DSQ measures how often a patient with EoE has trouble swallowing and the behavioral adaptations they subsequently use, as reported directly by patients.³

Significantly more patients receiving EOHILIA achieved histologic remission vs. placebo in Study 1 (53.1% vs. 1%).¹ In Study 2, 38% of EOHILIA patients achieved histologic remission vs. 2.4% of those in the placebo group. Absolute change from baseline in DSQ combined score in the EOHILIA vs. placebo groups in Study 1 was -10.2 (1.5) vs. -6.5 (1.8) and in Study 2, -14.5 (1.8) vs. -5.9 (2.1). During the last two weeks of each study, more patients receiving EOHILIA experienced no dysphagia or only experienced dysphagia that “got better or cleared up on its own” as compared to placebo, as measured by the DSQ. EOHILIA has not been shown to be safe and effective for the treatment of EoE for longer than 12 weeks. The most common adverse reactions (≥2% of patients receiving EOHILIA and at a rate greater than placebo) in Study 1 included: respiratory tract infection (13%), gastrointestinal mucosal candidiasis (8%), headache (5%), gastroenteritis (3%), throat irritation (3%), adrenal suppression (2%) and erosive esophagitis (2%). The safety profile of EOHILIA in Study 2 was generally similar to Study 1.¹

“For most of us, eating is a simple experience. But for people living with eosinophilic esophagitis, sitting down for a meal can include painful and difficult swallowing, chest pain and a choking sensation,” said Brandon Monk, senior vice president and head, U.S. Gastroenterology Business Unit, Takeda. “With EOHILIA, patients and their physicians now have the first and only FDA-approved oral treatment option for EoE that was shown during two 12-week clinical studies to reduce esophageal inflammation and improve the ability to swallow.”

EoE is a chronic, immune-mediated, inflammatory disease localized in the esophagus.⁴ Although the exact cause is unknown, it is believed to be triggered by a variety of stimuli including certain foods and environmental allergens.^5,6 The chronic inflammation of EoE can lead to a range of symptoms, which can vary by person and age, and include difficulty swallowing, vomiting and pain.⁷ Identifying EoE can be complex and delayed diagnosis is common among patients. If left untreated, the inflammation of EoE can worsen and narrow the esophagus, which can lead to food impaction (when food becomes stuck in the esophagus).^8,9 In fact, EoE is the leading cause of emergency room visits for food impaction.¹⁰

Takeda is assessing the financial impacts of the approval, including a reversal of impairment loss for intangible assets, on the fiscal year ending on March 31, 2024 (FY2023), but does not anticipate the impact to be material.

Indication and Limitations of Use

EOHILIA is indicated for 12 weeks of treatment in adult and pediatric patients 11 years of age and older with eosinophilic esophagitis (EoE).

EOHILIA has not been shown to be safe and effective for the treatment of EoE for longer than 12 weeks.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

EOHILIA is contraindicated in patients with hypersensitivity to budesonide. Serious hypersensitivity reactions, including anaphylaxis, have occurred with oral budesonide products.

WARNINGS AND PRECAUTIONS

Hypercorticism and Adrenal Axis Suppression

Systemic effects such as hypercorticism and adrenal axis suppression may occur. Monitor patients for signs and symptoms and consider reducing the dosage of EOHILIA. Use is not recommended in patients with severe hepatic impairment (Child‑Pugh Class C) and monitoring for signs and/or symptoms of hypercorticism is recommended in patients with moderate hepatic impairment (Child‑Pugh Class B).

Corticosteroids, including EOHILIA, can reduce the response of the hypothalamus-pituitary-adrenal (HPA) axis to stress. In situations where patients are subject to trauma, surgery, infection, or other stress situations, supplementation with a systemic corticosteroid is recommended.

Immunosuppression and Increased Risk of Infection

Corticosteroids, including EOHILIA, suppress the immune system and increase the risk of infection with any pathogen. Corticosteroid-associated infections can be mild, severe, and at times fatal. Monitor patients and consider discontinuation of EOHILIA if the patient develops an infection.

• Tuberculosis reactivation may occur. Closely monitor patients with latent tuberculosis or tuberculin reactivity while receiving EOHILIA.
• Varicella Zoster and Measles can be serious or fatal in non-immune patients taking corticosteroids. Avoid exposure. If a patient is exposed to varicella, prophylaxis with varicella zoster immune globulin may be indicated. If varicella develops, treatment with antiviral agents may be considered. If a patient is exposed to measles, prophylaxis with immunoglobulin may be indicated.
• Hepatitis B Virus Reactivation can occur. Prior to starting EOHILIA for patients who show evidence of hepatitis B infection, recommend consultation with physicians with expertise in managing hepatitis B regarding monitoring and consideration for hepatitis B antiviral therapy.
• Amebiasis: It is recommended that latent or active amebiasis be ruled out before starting EOHILIA in patients who have spent time in the tropics or have unexplained diarrhea.
• Avoid EOHILIA in patients with: systemic fungal infections, known or suspected Strongyloides (threadworm) infection, cerebral malaria, and active ocular herpes simplex.
• Localized Infections: In clinical trials, some patients developed Candida albicans infections in the mouth, throat, and esophagus. Instruct patients: do not eat or drink for 30 minutes after taking EOHILIA; after 30 minutes rinse mouth with water and spit without swallowing. If oropharyngeal or esophageal candidiasis develops, treat with appropriate antifungal therapy and consider discontinuing EOHILIA.

Erosive Esophagitis

Erosive esophagitis occurred in subjects who received EOHILIA in a 12-week clinical trial. None of the subjects had erosions at baseline esophagogastroduodenoscopy (EGD), and most were receiving concomitant therapy with a proton pump inhibitor (PPI). Advise patients or caregivers to report new onset or worsening signs or symptoms of erosive esophagitis to their healthcare provider. Consider endoscopic evaluation as appropriate.

Effect on Growth

Use of corticosteroids may cause a reduction of growth velocity in pediatric patients. Monitor the growth of pediatric patients on EOHILIA. The maximum recommended duration of treatment with EOHILIA is 12 weeks.

Symptoms of Steroid Withdrawal in Patients Transferred from Other Systemic Corticosteroids

Monitor patients who are transferred from corticosteroids with high systemic effects to corticosteroids with lower systemic availability, such as EOHILIA, since symptoms attributed to withdrawal of steroid therapy, including those of acute adrenal axis suppression or benign intracranial hypertension, may develop. Adrenocortical function monitoring may be required in these patients and the dose of corticosteroid treatment with high systemic effects should be reduced cautiously. Replacement of systemic corticosteroids with EOHILIA may unmask allergies (e.g., rhinitis and eczema) previously controlled by the systemic drug.

Other Corticosteroid Effects

Monitor patients with hypertension, diabetes mellitus, osteoporosis, peptic ulcer, glaucoma, or cataracts, or with family history of diabetes, glaucoma, or with other conditions where corticosteroids may have unwanted effects.

Kaposi’s Sarcoma

Kaposi’s sarcoma has been reported to occur in patients receiving corticosteroid therapy, most often for chronic conditions. Discontinuation of corticosteroids may result in clinical improvement of Kaposi’s sarcoma. The maximum recommended duration of treatment with EOHILIA is 12 weeks.

ADVERSE REACTIONS

Most common adverse reactions (≥2%) are: respiratory tract infection, gastrointestinal mucosal candidiasis, headache, gastroenteritis, throat irritation, adrenal suppression, and erosive esophagitis.

DRUG INTERACTIONS

Budesonide is a substrate for CYP3A4. Avoid concomitant use with CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, erythromycin, cyclosporine, and grapefruit juice), which can increase systemic budesonide concentrations.

USE IN SPECIFIC POPULATIONS

• Pregnancy: Hypoadrenalism may occur in infants born of mothers receiving corticosteroids during pregnancy. Infants should be carefully observed for signs of hypoadrenalism and managed accordingly.
• Lactation: Lactation studies have not been conducted with EOHILIA. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for EOHILIA and any potential adverse effects on the breastfed infant from EOHILIA, or from the underlying maternal condition.
• Hepatic Impairment: Not recommended in patients with severe hepatic impairment (Child-Pugh Class C). In patients with moderate hepatic impairment (Child-Pugh Class B), monitor for signs and/or symptoms of hypercorticism.

Please click here for full Prescribing Information.

Takeda’s Commitment to Gastroenterology

With this latest milestone, Takeda continues to demonstrate a commitment to meeting the very real needs of those living with gastrointestinal (GI) diseases. We believe that GI and liver diseases are life-disrupting conditions. Beyond a fundamental need for effective treatment options, we understand that improving patients’ lives also depends on their needs being recognized. With more than 35 years of experience in gastroenterology, Takeda has made significant strides in addressing patient needs with treatments for inflammatory bowel disease (IBD), acid-related diseases, short bowel syndrome (SBS) and motility disorders. We are making significant strides toward closing the gap on new areas of unmet need. Together with researchers, patient groups and more, we are working to advance scientific research and clinical medicine in GI.

About Takeda

Takeda is focused on creating better health for people and a brighter future for the world. We aim to discover and deliver life-transforming treatments in our core therapeutic and business areas, including gastrointestinal and inflammation, rare diseases, plasma-derived therapies, oncology, neuroscience, and vaccines. Together with our partners, we aim to improve the patient experience and advance a new frontier of treatment options through our dynamic and diverse pipeline. As a leading values-based, R&D-driven biopharmaceutical company headquartered in Japan, we are guided by our commitment to patients, our people and the planet. Our employees in approximately 80 countries and regions are driven by our purpose and are grounded in the values that have defined us for more than two centuries. For more information, visit www.takeda.com.

Important Notice

For the purposes of this notice, “press release” means this document, any oral presentation, any question-and-answer session and any written or oral material discussed or distributed by Takeda Pharmaceutical Company Limited (“Takeda”) regarding this release. This press release (including any oral briefing and any question-and-answer in connection with it) is not intended to, and does not constitute, represent or form part of any offer, invitation or solicitation of any offer to purchase, otherwise acquire, subscribe for, exchange, sell or otherwise dispose of, any securities or the solicitation of any vote or approval in any jurisdiction. No shares or other securities are being offered to the public by means of this press release. No offering of securities shall be made in the United States except pursuant to registration under the U.S. Securities Act of 1933, as amended, or an exemption therefrom. This press release is being given (together with any further information which may be provided to the recipient) on the condition that it is for use by the recipient for information purposes only (and not for the evaluation of any investment, acquisition, disposal or any other transaction). Any failure to comply with these restrictions may constitute a violation of applicable securities laws.

The companies in which Takeda directly and indirectly owns investments are separate entities. In this press release, “Takeda” is sometimes used for convenience where references are made to Takeda and its subsidiaries in general. Likewise, the words “we”, “us” and “our” are also used to refer to subsidiaries in general or to those who work for them. These expressions are also used where no useful purpose is served by identifying the particular company or companies.

Forward-Looking Statements

This press release and any materials distributed in connection with this press release may contain forward-looking statements, beliefs or opinions regarding Takeda’s future business, future position and results of operations, including estimates, forecasts, targets and plans for Takeda. Without limitation, forward-looking statements often include words such as “targets”, “plans”, “believes”, “hopes”, “continues”, “expects”, “aims”, “intends”, “ensures”, “will”, “may”, “should”, “would”, “could”, “anticipates”, “estimates”, “projects” or similar expressions or the negative thereof. These forward-looking statements are based on assumptions about many important factors, including the following, which could cause actual results to differ materially from those expressed or implied by the forward-looking statements: the economic circumstances surrounding Takeda’s global business, including general economic conditions in Japan and the United States; competitive pressures and developments; changes to applicable laws and regulations, including global health care reforms; challenges inherent in new product development, including uncertainty of clinical success and decisions of regulatory authorities and the timing thereof; uncertainty of commercial success for new and existing products; manufacturing difficulties or delays; fluctuations in interest and currency exchange rates; claims or concerns regarding the safety or efficacy of marketed products or product candidates; the impact of health crises, like the novel coronavirus pandemic, on Takeda and its customers and suppliers, including foreign governments in countries in which Takeda operates, or on other facets of its business; the timing and impact of post-merger integration efforts with acquired companies; the ability to divest assets that are not core to Takeda’s operations and the timing of any such divestment(s); and other factors identified in Takeda’s most recent Annual Report on Form 20-F and Takeda’s other reports filed with the U.S. Securities and Exchange Commission, available on Takeda’s website at: https://www.takeda.com/investors/sec-filings/ or at www.sec.gov. Takeda does not undertake to update any of the forward-looking statements contained in this press release or any other forward-looking statements it may make, except as required by law or stock exchange rule. Past performance is not an indicator of future results and the results or statements of Takeda in this press release may not be indicative of, and are not an estimate, forecast, guarantee or projection of Takeda’s future results.

Medical Information

This press release contains information about products that may not be available in all countries, or may be available under different trademarks, for different indications, in different dosages, or in different strengths. Nothing contained herein should be considered a solicitation, promotion or advertisement for any prescription drugs including the ones under development.

References

¹ EOHILIA (budesonide oral suspension) Prescribing Information. Takeda Pharmaceuticals U.S.A., Inc.

² Mewis J, Wagner NJ. Advances in Colloid and Interface Science. 2009; 214–227.

³ Hudgens S, Evans C, Phillips E, et al. J Patient Rep Outcomes. 2017;1(1):3.

⁴ Furuta GT, Katzka DA. N Engl J Med. 2015;373(17):1640-1648.

⁵ Clayton F, Peterson K. Gastrointest Endosc Clin N Am. 2018;28(1):1-14.

⁶ O’Shea KM, Aceves SS, Dellon ES, et al. Gastroenterology. 2018;154(2):333-345.

⁷ Muir AB, Brown-Whitehorn T, Gowin B, et al. Clin Exp Gastroenterol. 2019;12:391-399.

⁸ Shaheen NJ, Mukkada V, Eichinger CS, et al. Dis Esophagus. 2018;31(8):1-14.

⁹ Hirano I, Furuta GT. Gastroenterology. 2020;158(4):840-851.

¹⁰ Dellon ES, Hirano I. Gastroenterology. 2018;154(2):319-332.e3.

US-BOS-0537v1.0 02/24

Contacts

Media:
Japanese Media
Jun Saito
jun.saito@takeda.com
+81 3-3278-2325

U.S. and International Media
Amy McCarthy
amy.mccarthy@takeda.com
+1 781-496-7761

Publication: PR Newswire

Link: FDA Approves Takeda’s EOHILIA (budesonide oral suspension), the First and Only Oral Treatment in the U.S. for Eosinophilic Esophagitis (EoE) | Business Wire