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Gattex (teduglutide) Prior Authorization Program Summary
Policy Number: PH-1041
This program applies to Blue Partner, Commercial, GenPlus, NetResults A series, SourceRx and Health Insurance Marketplace formularies.
POLICY REVIEW CYCLE
Effective Date |
Date of Origin |
10-01-2024 |
|
FDA LABELED INDICATIONS AND DOSAGE
Agent(s) |
FDA Indication(s) |
Notes |
Ref# |
Gattex® (teduglutide) Single use vial kit |
Short Bowel Syndrome (SBS) in adults and pediatric patients 1 year of age and older who are dependent on parenteral support
|
|
1 |
See package insert for FDA prescribing information: https://dailymed.nlm.nih.gov/dailymed/index.cfm
CLINICAL RATIONALE
Short Bowel Syndrome |
Short bowel syndrome (SBS) results from the physical or functional loss of intestinal length due to disease or surgical resection. This leads to malabsorption of nutrients, water, and electrolytes relative to the amount of functional intestine remaining and which sections of the bowel are involved. Typically patients with SBS have a residual small intestine length of 200cm or less.(2,4,5) SBS can result in significant morbidity and mortality, reduced quality of life, and high health care costs. The symptoms, prognosis, and treatment of SBS can vary depending on which of the three groups it is classified into: jejunocolonic, jejunoileocolonic, and end jejunostomy. Typical signs and symptoms of SBS include diarrhea, dehydration, electrolyte abnormalities, malnutrition, and weight loss. (3,5) The goals of treatment are to:(4)
Diarrhea can be a bothersome and debilitating consequence for patients with SBS, having a negative impact on their quality of life. Several factors can contribute to diarrhea, including loss of gut surface area, gastric hypersecretion, and reduced gut hormone feedback mechanisms.(3) The use of antimotility agents long-term to control fluid and stool losses is a cornerstone of SBS therapy since limiting food intake to reduce diarrhea will exacerbate nutritional issues.(2,3,4,5) Loperamide is the preferred drug to treat diarrhea, but objective measures of stool output should guide the use of specific antidiarrheals. Other agents used include diphenoxylate, codeine, and tincture of opium.(5) Dehydration is also critical to avoid since it can result in rapid weight loss, fatigue, and kidney injury. Patients without a colon in continuity typically use a glucose-electrolyte oral rehydration solution (ORS) to enhance absorption of fluids and reduce secretion. Most patients with a colon do not require ORS for hydration since the colon has a large capacity to absorb water and sodium.(3,4,5) Long-term parenteral nutrition (PN) is often required to manage SBS, especially during the initial period following resection. Over 50% of adults with SBS can completely wean off PN within 5 years of diagnosis, but if not successfully accomplished within the first 2 years following resection the probability is less than 6%.(3,5) During the first 2 years following intestinal resection, intestinal adaptation occurs and the remaining bowel undergoes macroscopic and microscopic changes in order to increase its absorptive capacity. However, independence from PN may be accomplished through the use of intestinotrophic agents as part of a multidisciplinary approach.(3) Glucagon-like peptide-2 (GLP-2) analogs can be used to help wean patients with SBS off of PN after the period of maximal intestinal adaptation and work by aiding in absorption. They also help with the management of chronic diarrhea, malnutrition, dehydration, and electrolyte deficiencies. GLP-2 analogs should only be used after optimizing diet and more conventional SBS treatments.(3,5) |
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Efficacy |
Treatment of SBS in Adults Gattex (teduglutide) is a recombinant, degradation-resistant analog of naturally occurring human glucagon-like peptide-2 (GLP-2). GLP-2 is a peptide secreted by L-cells of the distal intestine in response to postprandial stimulation. GLP-2 is known to increase intestinal and portal blood flow, improve intestinal absorption, and inhibit gastric acid secretion. Gattex binds to the glucagon-like peptide-2 receptors, and activation results in the local release of multiple mediators including insulin-like growth factor (IGF)-1, nitric oxide, and keratinocyte growth factor (KGF).(1,3,5) The efficacy, safety, and tolerability of Gattex was evaluated in a randomized, double-blind, placebo-controlled, clinical study (Study 1) in adults with short bowel syndrome (SBS) who were dependent on parenteral nutrition/intravenous (PN/IV) support for at least 12 months and required PN at least 3 times per week. Investigators optimized the PN/I.V. volume of all patients, followed by a 4-week to 8-week period of fluid stabilization, prior to randomization. Patients were randomized (1:1) to placebo or Gattex 0.05mg/kg/day (subcutaneously once daily) for 24 weeks. PN/IV volume adjustments (up to 30% decrease) and clinical assessments were made at 2, 4, 8, 12, 20, and 24 weeks. Mean duration of PN/IV dependency prior to enrollment was 6 years, mean length of remaining small intestine was 77.3cm, and the colon was not in continuity in 44% of patients at baseline.(1) The primary efficacy endpoint was the percentage of patients who demonstrated a response at week 20 and maintained that response at week 24 (responder). A response was defined as a reduction from baseline in weekly PN/IV of 20% or greater (20%-100%). In the Gattex treatment group, 63% of patients were responders compared to only 30% of the placebo-treated patients (p=0.002). At Week 24, the mean reduction in weekly PN/IV volume was 4.4 Liters for Gattex-treated patients (from pre-treatment baseline of 12.9 Liters) versus 2.3 Liters for placebo-treated patients (from pre-treatment baseline of 13.2 Liters/week) (p<0.001).(1,6) Study 2 was a 2-year open-label extension of Study 1 in which 88 patients received Gattex 0.05 mg/kg/day. 76 patients who completed Study 1 elected to enroll in Study 2, and an additional 12 patients entered Study 2 who had been optimized and stabilized but not randomized in Study 1 because of closed enrollment. Patients who completed Study 2 are split into three groups for assessment of results: 30 patients received Gattex in Study 1 and Study 2 (TED/TED - 30 months of treatment), 29 patients received placebo in Study 1 and Gattex in Study 2 (PBO/TED - 24 months of treatment), and 6 were not in Study 1 but received Gattex in Study 2 (NT/TED - 24 months of treatment). Unique to the TED/TED group, 22 of the 30 patients in the group were considered responders from Study 1, and of those 22 patients, 21 (96%) sustained their response to Gattex in Study 2. Other results are shown in the table below:(1,7)
Study 3 was a randomized, double-blind, placebo-controlled, three parallel-group, study in adults with SBS who were dependent on PN/IV support for at least 12 months and required PN at least 3 times per week. After a period of optimization and stabilization similar to Study 1, patients were randomized to receive 24 weeks of one of the following treatment regimens: Gattex 0.05 mg/kg/day (n=35), Gattex 0.1 mg/kg/day (twice the recommended dose) (n=33), or placebo (n=16). Evaluation of the efficacy endpoint of response (defined as at least 20% reduction in PN/IV fluid from Baseline to Weeks 20 and 24) showed 46% of patient treated with Gattex 0.05mg/kg/day responded versus 6% on placebo. Study 4 was a blinded, uncontrolled extension of Study 3, in which 65 patients from Study 3 received Gattex for up to an additional 28 weeks of treatment. In the Gattex 0.05 mg/kg/day dose group, a 20% or greater reduction of PN/IV was achieved in 68% (17/25) of patients.(1) Treatment of SBS in Pediatrics Study 5 was a 24-week, multicenter study conducted in 59 pediatric patients aged 1 year through 17 years with SBS who were dependent on parenteral support (PS). Patients chose whether to receive Gattex or standard of care (SOC). Patients who chose to receive Gattex treatment were subsequently randomized in a double-blind manner to 0.025 mg/kg/day (n=24) or 0.05 mg/kg/day (n=26), while 9 patients enrolled in the SOC arm. At baseline, the mean PS volume was 60mL/kg/day and the mean PS infusion time was 7 days/week and 11 hours/day. At week 24 in patients treated with Gattex 0.05mg/kg/day (n=26), 69%(18/26) had a reduction in PS volume of at least 20, 38%(10/26) had a reduction in PS infusion time of greater than or equal to 1 day/week, and 12%(3/26) achieved enteral autonomy.(1)
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Safety |
Gattex has no FDA labeled contraindications for use but does carry warnings concerning neoplastic growth, intestinal obstruction, biliary and pancreatic disease, and fluid overload.(1) Gattex is a growth factor and has the potential to enhance the growth of gastrointestinal polyps, accelerate cancer growth, and cause hyperplastic changes including neoplasia.(1,5) Due to this risk, a colonoscopy of the entire colon should be done within 6 months prior to starting therapy in adult patients. If polyps are present, they should be removed and adherence to current polyp follow-up guidelines is recommended. If colorectal cancer is diagnosed, discontinue Gattex. In patients at increased risk for malignancy or patients who develop active non-gastrointestinal malignancy, the clinical decision to use Gattex should be made based on benefit-risk considerations. In pediatric patients, a fecal occult blood test should be performed within 6 months prior to starting therapy. If there is unexplained blood in the stool, a colonoscopy/sigmoidoscopy should be performed. For all patients, a follow-up colonoscopy (or alternate imaging) is recommended at the end of 1 year of Gattex therapy and at least every 5 years thereafter while on therapy.(1) Intestinal obstruction has been reported with Gattex in clinical trials. In patients who develop intestinal or stromal obstruction, Gattex should be temporarily discontinued while the patient is clinically managed. Gattex may be restarted when the obstructive presentation resolves.(1) Cholecystitis, cholangitis, cholelithiasis, and pancreatitis have been reported in clinical studies with Gattex treatment. Patients should undergo laboratory assessment of bilirubin, alkaline phosphatase, lipase, and amylase within 6 months prior to starting Gattex and at least every 6 months while on Gattex.(1) Fluid overload and congestive heart failure have been observed in clinical trials, which were felt to be related to enhanced fluid absorption associated with Gattex. If fluid overload occurs, parenteral support should be adjusted and Gattex treatment should be reassessed, especially in patients with underlying cardiovascular disease.(1) Gattex has the potential to increase absorption of concomitant oral medications. Agents that require titration or have a narrow therapeutic index require careful monitoring and possible dose adjustments.(1) |
REFERENCES
Number |
Reference |
1 |
Gattex prescribing information. Takeda Pharmaceuticals America, Inc. February 2024. |
2 |
American Gastroenterological Association medical position statement: Short bowel syndrome and intestinal transplantation. Gastroenterology. 2003;124(4):1105-1110. doi:10.1053/gast.2003.50139 |
3 |
Parrish CR, DiBaise JK. Managing the adult patient with short bowel syndrome. PubMed. 2017;13(10):600-608. |
4 |
Nightingale J, Woodward J. Guidelines for management of patients with a short bowel. Gut. 2006;55(suppl_4):iv1-iv12. doi:10.1136/gut.2006.091108 |
5 |
DiBaise JK, Iyer K, Rubio–Tapia A. AGA Clinical Practice Update on Management of Short Bowel Syndrome: Expert Review. Clinical Gastroenterology and Hepatology. 2022;20(10):2185-2194.e2. doi:10.1016/j.cgh.2022.05.032 |
6 |
Jeppesen PB, Pertkiewicz M, Messing B, et al. Teduglutide reduces need for parenteral support among patients with short bowel syndrome with intestinal failure. Gastroenterology. 2012;143(6):1473-1481.e3. doi:10.1053/j.gastro.2012.09.00 |
7 |
Schwartz LK, O’Keefe SJD, Fujioka K, et al. Long-Term teduglutide for the treatment of patients with intestinal failure associated with short bowel syndrome. Clinical and Translational Gastroenterology. 2016;7(2):e142. Doi:10.1038/ctg.2015.69 |
POLICY AGENT SUMMARY PRIOR AUTHORIZATION
Target Brand Agent(s) |
Target Generic Agent(s) |
Strength |
Targeted MSC |
Available MSC |
Final Age Limit |
Preferred Status |
|
||||||
Gattex |
teduglutide (rdna) for inj kit |
5 MG |
M ; N ; O ; Y |
N |
|
|
CLIENT SUMMARY – PRIOR AUTHORIZATION
Target Brand Agent Name(s) |
Target Generic Agent Name(s) |
Strength |
Client Formulary |
Gattex |
teduglutide (rdna) for inj kit |
5 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
PRIOR AUTHORIZATION CLINICAL CRITERIA FOR APPROVAL
Module |
Clinical Criteria for Approval |
|
Initial Evaluation Target Agent(s) will be approved when ALL of the following are met:
Length of Approval: 6 months *Step therapy requirement may not apply if a prior health plan paid for the medication - documentation of a paid claim may be required.
Renewal Evaluation Target Agent(s) will be approved when ALL of the following are met:
Length of Approval: 12 months |
This pharmacy policy is not an authorization, certification, explanation of benefits or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All pharmacy policies are based on (i) information in FDA approved package inserts (and black box warning, alerts, or other information disseminated by the FDA as applicable); (ii) research of current medical and pharmacy literature; and/or (iii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.
The purpose of Blue Cross and Blue Shield of Alabama’s pharmacy policies are to provide a guide to coverage. Pharmacy policies are not intended to dictate to physicians how to practice medicine. Physicians should exercise their medical judgment in providing the care they feel is most appropriate for their patients.
Neither this policy, nor the successful adjudication of a pharmacy claim, is guarantee of payment.
ALBP _ Commercial _ CSReg _ Gattex_PA _ProgSum_ 10-01-2024 _
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