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Home , Albiglutide, Insulin (medication), Insulin glargine, Insulin lispro

03 2016 eperzan® for type 2 mellitus drug assessment report No weight loss, no use www.dtb.navarra.es DTB_Navarre

Indications In studies with an active comparator, albiglu- abstract Adults with mellitus (Type 2 tide was proven to be statistically superior to DM): and and non-inferior to Albiglutide is a once-weekly GLP- · Monotherapy with albiglutide is indicated lispro and . In contrast, 1 analog. In Spain, it is only reim- when diet and exercise alone do not provide albiglutide was found to be statistically inferior bursed when administered in adequate glycaemic control in patients for to and . combination with other - whom use of is considered inap- lowering medicinal products and propriate due to contraindications or intole- weight loss is not required. rance. · In combination with other glucose-lowering Another antidiabetic Studies have not proven non-in- medicinal products including basal insulin, feriority vs liraglutide in reducing when these, together with diet and exercise, drug with no morbi- HbA1c. No comparative studies do not provide adequate glycaemic control. have been performed with exena- mortality data. Unlike tide once weekly. Mechanism of action and other analogs, it does Effectiveness data in terms of Albiglutide is a -like 1 (GLP- not help lose weight morbi-mortality are not available. 1) receptor that produces a glucose- dependent stimulation of insulin secretion and It has a neutral effect on weight, delays gastric emptying. Maximum concentra- in contrast with other drugs of the tion is reached 3-5h after administration and same family that help lose weight. its elimination half-life is 5 days approximately. A relevant effect of GLP-1 analogs is weight loss. However, albiglutide is not effective for The profile of adverse effects of Posology and method of administration weight loss and has not been proven to have albiglutide seems to be similar to The recommended dose is 30mg once weekly different effects from placebo. that of other GLP-1 analogs. The administered subcutaneously. The dose may incidence of and vomiting be increased to 50mg based on individual gly- Safety is lower in albiglutide than in lira- caemic response. It is available in the form of Adverse reactions glutide. pen injectors pre-filled with powder and solvent The incidence of in the clinical stu- which require previous reconstitution. dies was 0.3% for albiglutide compared to 0.1% Long-term safety is unknown. for comparators with or without antidiabetic There is concern about the asso- Clinical efficacy therapy at baseline. ciated risk of pancreatitis, pneu- The clinical efficacy of albiglutide has been Gastrointestinal events occurred with a hig- monia, cardiovascular disease, tested in eight phase III clinical trials, as mo- her frequency for albiglutide compared to all and pancreatic and thyroid tu- notherapy, as add-on therapy to metformin to comparators (38% vs 32%). The most frequent mors. two glucose-lowering agents, three glucose- gastrointestinal events were diarrhea, nausea, lowering agents, to insulin glargine, and also in vomiting and constipation. The majority occu- a study in patients with renal failure. Albiglutide rred within the first 6 months. The frequency of has been compared with sitagliptin, glimepiri- nausea and vomiting was lower with albuglu- de, insulin glargine, , liraglutide tide compared to liraglutide (7% vs 35%). The CLASSIFICATION and placebo. frequency of bowel obstruction was slightly The primary endpoint was change in HbA1c le- higher in the group receiving albiglutide with IMPORTANT vels with respect to baseline level at different respect to comparators (0.3% vs 0.2%). THERAPEUTIC time points according to the study considered Injection site reactions (typically including rash, 4 INNOVATION (from week 26 to 104). The main studies inclu- erythema, or itching at the injection site) occu- ded a total of 6,043 patients, of whom 3,358 rred in 15% of patients treated with albiglutide MODEST THERAPEUTIC were treated with albiglutide. and led to discontinuation in 2%. INNOVATION Statistically significant reductions were achie- The frequency of was low and 3 ved in HbA1c as compared to placebo alone similar to that observed with the comparators. SOME ADDED (-0.84 and -1.04 for doses of 30mg and 50mg, It increased when administered as add-on the- VALUE IN SPECIFIC respectively) and as add-on to other oral an- rapy to or insulin. 2 SITUATIONS tidiabetic drugs (-0.75 to -0.91), without any A higher incidence of atrial fibrillation/flutter significant weight loss. was observed in the group receiving albigluti- NO THERAPEUTIC 1 INNOVATION

INSUFFICIENT EVIDENCE The qualification assigned to the drug was agreed by the Drug Assessment Committees of Andalusia, Basque Country, Catalonia Institute of Health, Aragon and Navarre. The current report is based on the available information and is susceptible to be updated according to 0 the latest evidence. Let us remind the reader about the importance of notifying the Pharmacovigilance Centre when there are suspicions of adverse reactions to drugs. TREATMENT COST / 28 days (E) Drug interactions Albiglutide delays gastric emptying and may Insulin NPH 40 IU 28.39 impact the absorption of medicinal products.

Insulin lispro 40 IU 36.44 EMA’s Risk Management Plan Important risks identified: acute pancreati- Insulin glargine 40 IU 43.09 tis, gastrointestinal events, hypoglycemia, injection site reactions, immunogenecity, Glimepiride 2 mg 2.38 pneumonia and atrial fibrillation/flutter. Potentially important risks: cardiovascular Sitagliptin 100 mg 55.94 disease, medullary thyroid carcinoma, he- patotoxicity, pancreatic , bowel obs- Pioglitazone 30 mg 30.07 truction, non-clinical fetal and neonatal de- velopment toxicity and accelerated sexual 20 mg 124.57 maturation. Liraglutide 1.2 mg 128.95 Place in therapeutics 20 mcg Albiglutide is the only GLP-1 analog indica- 124.57 ted as monotherapy. However, since it has 0.75-1.5 mg 150.95 not been proven to be superior to other op- tions, it should not be administered alone. Weekly exenatide 2 mg 143.19 When adequate glycaemic control is not achieved despite the administration of a Albiglutide 30 mg - 50 mg 128.93 combination therapy, the third option con- sists of starting insulin therapy or using an oral glucose-lowering drug instead if the 0 20 40 60 80 100 120 140 160 patient is reluctant to use insulin or correct insulin administration cannot be guaranteed. Considering that there are no sufficient data de (1.3%) with respect to the comparators · Do not use albiglutide in patients with se- on the long-term safety and effectiveness group (0.5%) Small increases in heart rate (1 vere gastrointestinal disease, including of albiglutide in terms of morbi-mortality, to 2 bpm) were also observed. Transient is- gastroparesis. GLP-1 analogs can be used as add-on to a chemic attacks occurred more frequently in · After discontinuation, the effect of albiglu- combination therapy replacing insulin in patients receiving albiglutide (0.6% vs 0.2%). tide may continue over 3 to 4 weeks. This obese patients with a BMI >30-35 kg/m2 or A meta-analysis conducted to assess major should be taken into account when prescri- with important problems in insulinization, adverse cardiac events of albiglutide (acute bing another drug. or in case of ineffectiveness or intolerance myocardial infarction, stroke and CV death) There is no experience in patients with heart in previous therapies. Albiglutide therapy showed no differences with active compa- failure (NYHA III-IV) administered alone or in should be revised at six months and conti- rators. combination with prandial insulin, dypeptidyl nued only if HbA1c is reduced by at least 1.0 Pneumonia occurred in 2% of patients re- peptidase-4 (DPP-4) inhibitors or sodium/ and 3% weight loss at minimum is achieved ceiving albiglutide compared to 0.8% in the glucose cotransporter inhibitors. with respect to baseline values. comparators group. In combination therapy, albiglutide has Two cases of pancreatic cancer and another Usage in special situations been observed to be less effective in redu- two cases of thyroid cancer were reported Albiglutide should not be used during preg- cing HbA1c as compared to other GLP-1 in different phase III clinical trials in patients nancy nor in child-bearing age women who analogs (liraglutide) and has no effect on receiving albiglutide. do not use contraception. There are no ade- body weight. The potential improvement quate data to support the use of albiglutide in treatment adherence associated with Contraindications during breast-feeding. its weekly administration is not supported Hypersensitivity to the active substance or Dose adjustment is not required in patients by evidence, and albiglutide has not been to any of its excipients. with mild or moderate renal impairment. compared with exenatide administered once Albiglutide is not recommended in patients weekly. Its safety profile seems to be similar Special warnings and precautions with severe renal impairment or under he- to that of other GLP-1 analogs. Therefore, it for use modialysis. is difficult to find a place for albiglutide in the · Do not use in patients with type 1 DM or Dose adjustment is not recommended in pa- treatment of type 2 DM. . tients with impairment. No studies have · Patients should be informed of the cha- been conducted in this population. Presentation racteristic symptoms of acute pancreati- There are no data on the safety and effec- Eperzan® (GlaxoSmithKline) 30 mg 4 pens tis. If pancreatitis is suspected, albiglutide tiveness of albiglutide in patients aged < 18 (128.93 €); 50 mg 4 pens (128.93 €). should be discontinued. years. · Patients may require a lower dose of syl- Similar results have been obtained in pa- References phonylureas or insulin as add-on therapy tients aged 65 years as compared to the ge- Based on the Therapeutic Positioning Re- to albiglutide to reduce the risk of hypogly- neral population. However, there are limited port. caemia. clinical data on patients 75 years.

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