Effective Date

Date of Origin   

10-01-2024           

10-01-2024

Eohilia™

(budesonide)

Oral suspension

Treatment of eosinophilic esophagitis (EoE) for 12 weeks in adult and pediatric patients aged 11 years and older

Limitations of use:

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

1

Eosinophilic Esophagitis

Eosinophilic Esophagitis (EoE) is an allergen/immune-mediated disease characterized by symptoms of esophageal dysfunction and marked eosinophilic inflammation of the esophageal mucosa in the absence of secondary causes. EoE has dramatically increased in prevalence over the years. EoE is characterized by symptoms related to esophageal dysfunction and histologically with eosinophil-predominant inflammation (a peak count of greater than or equal to 15 eosinophils per high-power field on esophageal biopsy). Atopic and allergic inflammatory conditions commonly occur concomitantly with EoE.(2)

The symptoms of EoE are age dependent. Young children may refuse to eat, have decreased appetite, recurring abdominal pain, trouble swallowing, and vomiting. Young adults and adults have the same symptoms, but often struggle to swallow dry or dense, solid foods due to inflammation. Food impaction is a common cause for emergency room visits in patients with EoE. Patients may also have concurrent gastroesophageal reflux disease (GERD). EoE is a progressive disease if left untreated. The chronic inflammation can lead to tissue fibrosis and strictures in the esophagus that require esophageal dilation.(3)

The diagnosis of EoE is suspected on the basis of chronic symptoms such as dysphagia, food impaction, food refusal, failure to progress with food introduction, heartburn, regurgitation, vomiting, chest pain, odynophagia, abdominal pain, and malnutrition. Due to the wide range of chronic symptoms, the diagnosis should be highly considered in the presence of concomitant atopic conditions and if there are endoscopic findings. Endoscopic findings associated with EoE include esophageal rings, longitudinal furrows, exudates, edema, strictures, or narrow caliber esophagus. Assessment of non-EoE disorders and esophageal biopsy are required to confirm the diagnosis of EoE, with at least 15 eosinophils (eos)/ high-power field (hpf) present on esophageal biopsy.(4)

Nonpharmacological treatment of EoE includes dilation and diet. Dilation is only conditionally recommended for patients with dysphagia associated with strictures due to EoE, noting that the dilation does not address the underlying inflammation.(5) Both elemental and elimination diets have been shown to be effective, however, barriers of adherence and cost make this treatment modality feasible only for select patients.(5,6)

Proton pump inhibitors (PPIs) are a first line treatment option for patients with EoE, and PPI monotherapy is widely used in practice. PPIs have a longstanding safety profile and have shown to be effective based on symptom response and histological remission. The 2020 American Gastroenterological Association (AGA) and the Joint Task Force on Allergy-Immunology Practice Parameters (JTF) guidelines conditionally recommend their use while the 2022 British Society of Gastroenterology (BSG) and British Society of Pediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) guidelines strongly recommend their use.(5,6)

The AGA/JTF and BSG/BSPGHAN both strongly recommend the use of topical glucocorticoids for the treatment of EoE. Studies showed that topical (swallowed) budesonide or topical fluticasone induced histological remission significantly better than placebo and had similar adverse events to placebo. Due to the chronic nature of the disease and the risk of progression, topical corticosteroids may be continued as maintenance therapy after remission with short term use. A clinical review of the patient should guide this decision based on preference to avoid long term adverse effects of topical steroids, or to prevent undesirable outcomes of the disease itself.(5,6)

Efficacy

The efficacy and safety of Eohilia 2 mg twice daily were evaluated in two multicenter, randomized, double-blind, parallel-group, placebo-controlled 12-week studies (Study 1 [NCT02605837] and Study 2 [NCT01642212]). Eligible subjects in both studies had esophageal inflammation defined as greater than or equal to 15 eosinophils/high-power field (hpf) from at least 2 levels of the esophagus at baseline following a treatment course of a proton pump inhibitor (PPI) either prior to or during screening and at least 4 days of dysphagia as measured by the Dysphagia Symptom Questionnaire (DSQ) over a 2-week period prior to randomization. Concomitant use of stable doses of inhaled or intranasal steroids (for conditions other than EoE), PPIs, H2-receptor antagonists, antacids, antihistamines or anti-leukotrienes, and maintenance immunotherapy was allowed. In Study 1, subjects were enrolled after maintaining a stable diet for at least 3 months prior to screening and were instructed to maintain a stable diet throughout the study. Subjects were excluded if they were on a full liquid or 6-food elimination diet. In Study 2, subjects were instructed to maintain a stable diet throughout the study. In both studies, subjects were instructed to not eat or drink for 30 minutes after taking the drug and then to rinse their mouth with water and spit out the contents without swallowing prior to resuming normal oral intake.(1)

A total of 318 subjects (277 adults and 41 pediatric subjects) were randomized and received at least one dose of study drug (Eohilia or placebo) in Study 1. The mean age of the study population was 34 years (range 11 to 56 years). Over 80% of the subjects were on concomitant PPI. The mean (SD) DSQ combined scores at baseline were 30.3 (13.9) and 30.4 (13.1) in the EOHILIA and placebo groups, respectively.(1)

A total of 92 subjects (58 adults and 34 pediatric subjects) were randomized and received at least one dose of study drug (Eohilia or placebo) in Study 2. The mean age of the study population was 22 years (range 11 to 42 years). Over 65% of the subjects were on concomitant PPI. The mean (SD) DSQ combined scores at baseline were 30.7 (16.0) and 29.0 (13.5) in the EOHILIA and placebo groups, respectively.(1)

Efficacy endpoints for both studies were the proportion of patients with a histologic response (defined as a peak eosinophil count of less than or equal to 6/hpf across all available esophageal levels) and the absolute change from baseline in subject-reported DSQ combined score after 12 weeks of treatment. Results are shown in the table below:(1)

*Total biweekly DSQ scores range from 0 to 84, higher scores indicate greater frequency and severity of dysphagia

In both studies, during the last 2 weeks of the 12-week treatment periods, a greater proportion of subjects randomized to Eohilia experienced no dysphagia or only experienced dysphagia that “got better or cleared up on its own” compared to placebo, as measured by the subject-reported DSQ.(1)

In Study 1, 48 subjects from the Eohilia treatment arm entered a double-blind randomized withdrawal extension study and either received Eohilia 2mg twice daily or placebo for up to an additional 36 weeks. No statistically significant difference was demonstrated between the two groups based on eosinophil count and/or clinical symptoms measured by the DSQ at Week 36.(1)

Safety

Eohilia is contraindicated in patients with hypersensitivity to budesonide. Serious hypersensitivity reactions, including anaphylaxis, have occurred with oral budesonide products.(1)

1

Eohilia prescribing information. Takeda Pharmaceuticals America, Inc. February 2024.

2

O’Shea K, Aceves SS, Dellon ES, et al. Pathophysiology of Eosinophilic Esophagitis. Gastroenterology. 2018;154(2):333-345. doi:10.1053/j.gastro.2017.06.065

3

The American Academy of Allergy, Asthma & Immunology. Eosinophilic Esophagitis: Symptoms, Diagnosis & Treatment. https://www.aaaai.org/conditions-treatments/related-conditions/eosinophilic-esophagitis. Last revised May 1, 2023.

4

Dellon ES, Liacouras CA, Molina‐Infante J, et al. Updated International Consensus Diagnostic Criteria for Eosinophilic Esophagitis: Proceedings of the AGREE Conference. Gastroenterology. 2018;155(4):1022-1033.e10. doi:10.1053/j.gastro.2018.07.009

5

Hirano I, Chan ES, Rank MA, et al. AGA Institute and the Joint Task Force on Allergy-Immunology Practice Parameters Clinical Guidelines for the Management of Eosinophilic Esophagitis. Gastroenterology. 2020;158(6):1776-1786. doi:10.1053/j.gastro.2020.02.038

6

Dhar A, Haboubi H, Attwood S, et al. British Society of Gastroenterology (BSG) and British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) joint consensus guidelines on the diagnosis and management of eosinophilic oesophagitis in children and adults. Gut. May 2022:gutjnl-327326. doi:10.1136/gutjnl-2022-327326

Eohilia

budesonide oral suspension

2 MG/10ML

M ; N ; O ; Y

N

Eohilia

budesonide oral suspension

2 MG/10ML

1800

mLs

90

DAYS

Eohilia

budesonide oral suspension

2 MG/10ML

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Eohilia

budesonide oral suspension

2 MG/10ML

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

PA

Target Agent(s) will be approved when ALL of the following are met:

1. The patient has a diagnosis of eosinophilic esophagitis (EoE) AND the patient's diagnosis was confirmed by ALL of the following:
   1. Chronic symptoms of esophageal dysfunction AND
   2. Greater than or equal to 15 eosinophils per high-power field on esophageal biopsy AND
   3. Other causes that may be responsible for or contributing to symptoms and esophageal eosinophilia have been ruled out AND
2. ONE of the following:
   1. The patient has tried and had an inadequate response to ONE standard corticosteroid therapy (i.e., swallowed budesonide nebulizer suspension, swallowed fluticasone MDI) used in the treatment of EoE OR
   2. The patient has an intolerance or hypersensitivity to standard corticosteroid therapy used in the treatment of EoE that is not expected to occur with the requested agent OR
   3. The patient has an FDA labeled contraindication to ALL standard corticosteroid therapies used in the treatment of EoE that is not expected to occur with the requested agent OR
   4. The patient has tried and had an inadequate response to ONE proton pump inhibitor (PPI) used in the treatment of EoE OR
   5. The patient has an intolerance or hypersensitivity to PPI therapy used in the treatment of EoE OR
   6. The patient has an FDA labeled contraindication to ALL PPI therapies used in the treatment of EoE AND
3. If the patient has an FDA labeled indication, then ONE of the following:
   1. The patient’s age is within FDA labeling for the requested indication for the requested agent OR
   2. There is support for using the requested agent for the patient’s age for the requested indication AND
4. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., gastroenterologist, allergist, immunologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
5. The patient does NOT have any FDA labeled contraindications to the requested agent AND
6. ONE of the following:
   1. The patient has not previously been treated with a course of therapy (12 weeks) with the requested agent OR
   2. The patient has previously been treated with a course of therapy with the requested agent, AND there is support for an additional course of therapy with the requested agent

Length of Approval: 3 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

*Step therapy requirement may not apply if a prior health plan paid for the medication - documentation of a paid claim may be required.

Universal QL

Quantity limit for the Target Agent(s) will be approved when ONE of the following is met:

1. The requested quantity (dose) does NOT exceed the program quantity limit OR 
2. The requested quantity (dose) exceeds the program quantity limit AND ONE of the following:
   1. BOTH of the following:
      1. The requested agent does NOT have a maximum FDA labeled dose for the requested indication AND
      2. There is support for therapy with a higher dose for the requested indication OR
   2. BOTH of the following:
      1. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND
      2. There is support for why the requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does NOT exceed the program quantity limit OR
   3. BOTH of the following:
      1. ​​​​​​​The requested quantity (dose) exceeds the maximum FDA labeled dose for the requested indication AND
      2. There is support for therapy with a higher dose for the requested indication​​​​​​​

Length of Approval: up to 3 months