Effective Date

Date of Origin   

10-01-2025           

10-01-2024

Eohilia™

(budesonide)

Oral suspension

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

Limitation 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 (EoE)

Eosinophilic esophagitis (EoE) is a chronic allergen/immune-mediated disease characterized by esophageal dysfunction and marked eosinophilic inflammation of the esophageal mucosa in the absence of secondary causes. EoE is characterized histologically with eosinophil-predominant inflammation confined to the esophagus. EoE is a progressive disease if left untreated, and the chronic inflammation can lead to tissue fibrosis and strictures in the esophagus. Atopic and allergic inflammatory conditions (e.g., asthma, atopic dermatitis, food/seasonal allergy) commonly occur concomitantly with EoE.(2)

The symptoms of EoE are age dependent. Young children and infants may refuse to eat or have abdominal pain, trouble swallowing, or vomiting. In addition, persistent feeding difficulties may lead to weight loss or a failure to thrive. Older children and adults most commonly present with dysphagia to solid food, but may also have symptoms of chest pain or heartburn. Food impaction is a common cause for emergency room visits in these patients.(2,3)

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. When a patient's clinical presentation is suggestive of EoE, an esophageal biopsy should be performed. Patients with esophageal eosinophilia of greater than or equal to 15 eosinophils (eos) per high-power field (hpf) would be considered to have clinically suspected EoE. The eosinophilic infiltration should be isolated to the esophagus.(4) It should be brought into consideration that diet and medications, including those used to treat EoE, may lead to a falsely negative result on esophageal biopsy, and an endoscopy would ideally be performed while on no treatment to maximize diagnostic sensitivity.(6) The diagnosis is then finalized after evaluation shows that there are no significant other causes of symptoms and/or esophageal eosinophilia.(4)

A summary of the EoE diagnostic criteria is as follows:(4)

1. Symptoms of esophageal dysfunction and a clinical presentation suggestive of EoE
   [Next step: perform esophageal biopsy]
2. Esophageal eosinophilia of greater than or equal to 15 eos/hpf
   [Next step: evaluate for the presence of non-EoE disorders that cause or potentially contribute to esophageal eosinophilia]
3. Other causes of symptoms and/or esophageal eosinophilia have been excluded

Nonpharmacological treatment of EoE includes esophageal dilation and diet. Esophageal dilation is used to treat strictures and luminal narrowing and is conditionally recommended only for patients with dysphagia associated with strictures, noting that the dilation does not address the underlying inflammation or pathogenesis.(5,6) 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)

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.(5,6) In EoE, PPIs can provide benefit beyond acid suppression by decreasing expression of eotaxin-3 (the main cytokine that recruits eosinophils to the esophagus), improving esophageal barrier function, and helping to maintain esophageal epithelial transcriptional homeostasis.(6)

Swallowed topical corticosteroids (STCs) are also a first line treatment option for patients with EoE. Both the American Gastroenterological Association (AGA) and the American College of Gastroenterology (ACG) strongly recommend their use.(5,6) STCs have demonstrated histologic efficacy, a reduction in symptoms (including dysphagia), and improvement in endoscopic disease activity.(6) In short term use of 3 months or less, STCs have a favorable safety profile, and studies have shown no increased risk of adverse events compared to placebo outside of candidal infection.(5,6) Options for STCs include fluticasone propionate or budesonide. Fluticasone propionate is swallowed using commercially available metered dose inhalers (MDIs) and budesonide is consumed via an oral slurry using aqueous budesonide respules mixed with sucralose, honey, or maple syrup. An oral budesonide suspension is also commercially available for the treatment of EoE. Off-label use of asthma preparations of corticosteroids adapted for esophageal delivery have comparable histologic efficacy with preparations designed for esophageal delivery. A trial comparing fluticasone to budesonide showed similar efficacy between the two drugs, and either one is a reasonable choice for initial treatment based on patient/provider preference.(6)

Diet, PPIs, and STCs work by treating the inflammatory component of the disease and can also lead to benefit in esophageal caliber. A single anti-inflammatory therapy should be used for initial treatment of EoE and should be selected based on disease characteristics and patient preference. Combination therapy with multiple anti-inflammatory drug therapies is not recommended due to a current lack of data.(6) Treatment response should be assessed by clinical, endoscopic, and histologic disease activity 8 to 12 weeks after starting the new therapy.(3,6) Assessing clinical symptom improvement alone is not sufficient since there is only a modest correlation between symptomatic improvement and histologic remission or endoscopic response. If adequate response is achieved, the current medication can be continued, noting that a decrease in dose may be warranted and desired for maintenance therapy. If a patient has non-response with initial treatment, a change in medication, dose, or formulation may be considered prior to stepping up to therapy with a biologic agent.(6)

Maintenance therapy is needed for the treatment of EoE due to the chronic relapsing nature of the disease and the current understanding that it is a lifelong condition. When EoE treatment is stopped, regardless of the treatment used, disease activity and flares almost always recur. Fibrostenotic progression also occurs in most patients. Data supports the long-term efficacy of PPIs and dietary elimination for maintenance therapy, but STCs may also be used. Using STCs for maintenance therapy comes with the risk of long-term adverse effects (such as candidal infection or adrenal insufficiency), and they may also have a loss of response over time. If using STCs long-term, the lowest effective dose should be used. Studies involving the discontinuation of STCs following initial therapy have shown that the median time to symptom relapse after stopping treatment is about 3 months.(6) Patients with rapid symptomatic/histologic relapse following STC initial therapy should consider reinitiating STC therapy based on shared decision-making. Patients with severe dysphagia, food impaction, or high-grade esophageal stricture may also consider reinitiation or maintenance therapy with a STC.(8)

A biologic agent may be considered as a step-up therapy option in patients who do not respond to initial pharmacologic treatment, especially PPI non-responders. Dupilumab, an interleukin (IL)-4 receptor alpha antagonist, has been shown to decrease dysphagia symptoms and improve endoscopic and histologic severity in patients with EoE. Response should be assessed between 12 and 24 weeks after therapy is initiated. Data supports maintenance therapy with a biologic agent, and dupilumab demonstrated continued histologic, endoscopic, and symptom efficacy in patients treated for 52 weeks, with some patients having a higher response rate after 52 weeks than at 24 weeks.(6)

The treatment algorithm for pediatric patients aligns with how the disease is managed in adults. This includes the use of biologic agents (e.g., dupilumab) for difficult-to-treat patients that do not respond to, or are intolerant of, alternative treatments.(3,6)

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 (eos)/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 subjects 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 2 mg twice daily or placebo for up to an additional 36 weeks. No statistically significant difference was demonstrated between the two groups for prespecified efficacy endpoints based on eosinophil count and/or clinical symptoms measured by the DSQ at Week 36.(1) In the placebo arm of this extension study (n=23), 10 of the 23 subjects relapsed during the 36 weeks of withdrawal, and 7 of these 10 subjects reinitiated treatment with Eohilia 2 mg twice daily. Relapse was defined as a subject having a histologic finding of greater than or equal to 15 eos/hpf in addition to at least 4 days of dysphagia within the 2 weeks before the study visit. Of the 7 subjects who reinitiated therapy with Eohilia, 1 subject reinitiated at Week 8 due to the result of an unscheduled upper endoscopy, and the remaining 6 subjects reinitiated at either Week 16, 20, or 28 (2 subjects at each time period).(7)

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. May 2024.

2

Roussel JM, Pandit S. Eosinophilic Esophagitis. [Updated 2023 Aug 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459297/

3

Amil‐Dias J, Oliva S, Papadopoulou A, et al. Diagnosis and management of eosinophilic esophagitis in children: An update from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN). Journal of Pediatric Gastroenterology and Nutrition. 2024;79(2):394-437. doi:10.1002/jpn3.12188

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

Dellon ES, Muir AB, Katzka DA, et al. ACG Clinical Guideline: Diagnosis and Management of Eosinophilic Esophagitis. The American Journal of Gastroenterology. 2025;120(1):31-59. doi:10.14309/ajg.0000000000003194

7

Dellon ES, Collins MH, Katzka DA, et al. Long-Term treatment of eosinophilic esophagitis with budesonide oral suspension. Clinical Gastroenterology and Hepatology. 2021;20(7):1488-1498.e11. doi:10.1016/j.cgh.2021.06.020

8

Dellon ES, Gonsalves N, Hirano I, Furuta GT, Liacouras CA, Katzka DA. ACG Clinical Guideline: Evidenced Based Approach to the Diagnosis and Management of Esophageal Eosinophilia and Eosinophilic Esophagitis (EOE). The American Journal of Gastroenterology. 2013;108(5):679-692. doi:10.1038/ajg.2013.71

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 ; SourceRx-Performance

Eohilia

budesonide oral suspension

2 MG/10ML

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

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 has been 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. The patient has ONE of the following:
   1. Has tried and had an inadequate response to ONE standard corticosteroid therapy (i.e., swallowed budesonide nebulizer suspension, swallowed fluticasone from a metered dose inhaler [MDI]) used in the treatment of EoE after at least an 8-week duration of therapy OR
   2. Has an intolerance or hypersensitivity to ONE standard corticosteroid therapy used in the treatment of EoE that is not expected to occur with the requested agent OR
   3. 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. Has tried and had an inadequate response to ONE proton pump inhibitor (PPI) used in the treatment of EoE after at least an 8-week duration of therapy OR
   5. Has an intolerance or hypersensitivity to ONE PPI used in the treatment of EoE OR
   6. Has an FDA labeled contraindication to ALL PPIs 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