Effective Date

Date of Origin   

10-01-2024           

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

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)

• Provide nutrition, water, and electrolytes necessary to maintain health, with normal body weight or growth
• Use oral/enteral nutrition in preference to parenteral nutrition whenever the gut is functional and can absorb sufficient nutrients, water, and electrolytes
• Reduce the complications resulting from the underlying disease, intestinal failure, and/or nutritional/fluid support
• Achieve a good quality of life

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)

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)
Study 6 was a prospective, open-label, long-term extension study of pediatric patients who completed Study 5. Patients received additional treatment with Gattex 0.05 mg/kg subcutaneously once daily if they deteriorated or stopped improving after discontinuation of prior Gattex treatment. 87% (13/15) of patients required additional treatment with Gattex. At the end of week 24 (total treatment for a mean of 40 weeks), efficacy results were similar to those achieved at the end of 24 weeks treatment in Study 5. One additional patient achieved enteral autonomy during follow-up in Study 6.(1)

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)

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

Gattex

teduglutide (rdna) for inj kit

5 MG

M ; N ; O ; Y

N

Gattex

teduglutide (rdna) for inj kit

5 MG

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

Initial Evaluation

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

1. ONE of the following:
   1. The patient has a diagnosis of short bowel syndrome (SBS) and ALL of the following:
      1. The patient has less than 200 cm of functional small intestine AND
      2. The patient has tried and had an inadequate response to maximal use of TWO anti-diarrheal agents (e.g., loperamide, diphenoxylate) used concomitantly with oral rehydration solution AND
      3. The patient is currently receiving parenteral nutrition/intravenous fluids (PN/IV) at least 3 days per week AND
      4.  ONE of the following:
         1. The patient is a pediatric patient at least 1 year of age AND BOTH of the following:
            1. A fecal occult blood test has been performed within 6 months prior to initiating treatment with the requested agent AND
            2. ONE of the following:
               1. There was no unexplained blood in the stool OR
               2. There was unexplained blood in the stool AND a colonoscopy or a sigmoidoscopy was performed OR
         2. The patient is an adult AND BOTH of the following:
            1. The patient has had a colonoscopy within 6 months of initiating treatment with the requested agent AND
            2. If polyps were present at this colonoscopy, the polyps were removed OR
   2. The patient has another FDA labeled indication for the requested agent AND
2. 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
3. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., gastroenterologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
4. The patient does NOT have any FDA labeled contraindications to the requested agent AND
5. The requested quantity (dose) is within FDA labeled dosing for the requested indication

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:  

1. The patient has been previously approved for the requested agent through the plan’s Prior Authorization process [Note: patients not previously approved for the requested agent will require initial evaluation review] AND
2. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., gastroenterologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
3. The patient has had clinical benefit with the requested agent AND
4. The patient does NOT have any FDA labeled contraindications to the requested agent AND
5. The requested quantity (dose) is within FDA labeled dosing for the requested indication

Length of Approval: 12 months