REVESTIVE

What it is

REVESTIVE contains teduglutide , which is a 33 amino acid glucagon-like peptide-2 (GLP-2) analogue manufactured using a strain of Escherichia coli modified by recombinant DNA technology . The pharmaceutical form is powder for solution for injection . Each single-use vial contains 5 mg of teduglutide as a white lyophilised powder . Teduglutide is an analogue of naturally occurring human GLP-2, a peptide secreted by L-cells of the distal intestine, 33 amino acids in length with an amino acid substitution of alanine by glycine at the second position of the N-terminus, which results in resistance to in vivo degradation by the enzyme dipeptidyl peptidase-IV (DPP-IV), resulting in an extended half-life . Teduglutide has been shown to preserve mucosal integrity by promoting repair and normal growth of the intestine through an increase of villus height and crypt depth .

Approved indications

REVESTIVE is indicated for the treatment of adult and paediatric patients 2 years of age and above with Short Bowel Syndrome (SBS) who are dependent on parenteral support . — Short Bowel Syndrome (SBS) in patients dependent on parenteral support (adult and paediatric patients 2 years and above)

Dosing overview

The recommended dose of REVESTIVE for both adults and paediatric patients (aged 2 years and above) is 0.05 mg/kg body weight administered by subcutaneous injection once daily . REVESTIVE should not be administered to children weighing less than 10 kg . In adult or paediatric patients with moderate and severe renal impairment (creatinine clearance less than 50 mL/min) and end-stage renal disease, the dose should be reduced by 50% . No dose adjustment is necessary in patients above the age of 65 years . No dose adjustment is necessary for patients with mild and moderate hepatic impairment based on a study conducted in Child-Pugh grade B subjects . The reconstituted solution must be injected subcutaneously into a cleaned area on the abdomen, or if this is not possible, on the thigh using a thin needle for subcutaneous injection . REVESTIVE should not be administered intravenously or intramuscularly .

Key safety warnings

Colorectal polyps were identified during clinical trials; colonoscopy of the entire colon with removal of polyps should be done within 6 months prior to starting treatment with teduglutide . A follow-up colonoscopy (or alternate imaging) is recommended between 1-2 years after initiating teduglutide . Based on pharmacologic activity and findings in animals and humans, teduglutide has the potential to cause hyperplastic changes, including neoplasia, in the small bowel and hepatobiliary tract, although these observations were not confirmed in clinical studies of more than one year duration . Patients should be monitored clinically for small bowel and hepatobiliary neoplasia, and upper GI endoscopy or other imaging is recommended before and during treatment with teduglutide per clinical discretion . Cholecystitis, cholangitis, and cholelithiasis have been reported in clinical studies; patients should undergo laboratory assessment of bilirubin and alkaline phosphatase prior to starting teduglutide and while on teduglutide . Pancreatic adverse events such as chronic and acute pancreatitis, pancreatic duct stenosis, pancreas infection and increased blood amylase and lipase have been reported in clinical studies; patients should undergo laboratory assessment of lipase and amylase prior to starting teduglutide and while on teduglutide . Careful adjustment of parenteral support is required in patients taking teduglutide to avoid fluid overload or dehydration; electrolyte balance and fluid status should be carefully monitored throughout treatment, especially during initial therapeutic response and discontinuation of teduglutide treatment . Fluid overload and congestive heart failure have been observed in clinical trials, occurring most frequently during the first 4 weeks of therapy and decreasing over time .

Contraindications

Hypersensitivity to the active ingredient or to any of the excipients is a contraindication . Active or suspected malignancy is a contraindication . Patients with a history of malignancies in the gastrointestinal tract including the hepatobiliary system within the last 5 years are contraindicated from use .

PBS listing

REVESTIVE 5 mg powder for injection with diluent is listed on the PBS with 6 items, authority required restriction, and an ex-manufacturer price of A$19,710.60 .

Regulatory history

REVESTIVE teduglutide 5 mg powder for solution for injection vial with diluent pre-filled syringe was first listed on the ARTG on 2017-05-19 . The AusPAR approval date was 2017-05-17; the TGA decided to approve the registration of REVESTIVE for treatment of adult patients with Short Bowel Syndrome who are dependent on parenteral support, concluding that the benefits of the medicine outweigh the risks for the target patient population . In March 2019, the PBAC recommended REVESTIVE for Short Bowel Syndrome in patients dependent on parenteral nutrition for survival under the Highly Specialised Drug Program with authority required listing . In March 2021, the PBAC recommended REVESTIVE for short bowel syndrome in paediatric patients with Type III (chronic) SBS with intestinal failure and for paediatric patients with SBS . In November 2022, the PBAC recommended a change in the definition of treatment failure from 'last assessment' to 'baseline' and removal of the trial treatment break as a requirement, while still allowing voluntary treatment breaks .