Waylivra treatment

Treatment with Waylivra®

Getting started with Waylivra®

Which patient is appropriate?

  • Fasting triglyceride level repeatedly > 885 mg/dl (> 10 mmol/l).1
  • Genetically confirmed FCS.1
  • A genetic defect triggers the disease, independent of other mutations or polymorphisms. This is currently shown for the 8 genes: LPL, APOC2, APOA5, CREB3L3, GCKR, GPIHBP1, LMF1, GPD-1.2,3 Other genes may be identified in the future.
  • Diet and triglyceride-lowering therapy does not lead to normalization of values.1
  • Existing risk of pancreatitis. Patients with FCS and severe hypertriglyceridemia have a 360-fold higher risk of acute pancreatitis compared to controls.4
  • At the start of therapy: platelet count > 140 × 109/l.1

Waylivra® is the only therapy licensed* to treat familial chylomicronemia syndrome (FCS), as an adjunct to diet in adult patients with genetically confirmed disease and at high risk for pancreatitis, in whom response to diet and triglyceride lowering therapy has been inadequate.1

*by the European Medicines Agency

What is the right application and dosing?
 

Waylivra® is a once-weekly, self-administered injection delivered in a single-use prefilled syringe.1

Dosing regime of Waylivra®:1

Tips for self-injection
 

The first injection administered by the patient or a caregiver should be given under the guidance of a qualified healthcare professional. The patients or caregivers must be trained in the use of the medicinal product in accordance with the instructions in the patient information leaflet.

In order to avoid reactions at the injection site, the Waylivra® prefilled syringe should be at room temperature before injection and the patient should apply a cold pack to the injection site after injection. It is also advisable to inject the medication slowly and to change the injection site with each injection.

Injection tracker

Inject slowly.1

  • Squeeze the skin around the injection site
  • Do not touch the syringe plunger when inserting the needle into the skin, so that no medication is injected intracutaneously
  • Inject the medication slowly so that it can spread better.
  • Cooling the injection site reduces pain, redness or discomfort

Injection only with pre-filled syringes at room temperature1

  • Remove from the refrigerator at least 30 minutes before use
  • Do not heat the syringe in any other way, e.g. in the microwave or in warm water

Select alternating injection sites1

  • Avoid injection sites where clothing could press or rub
  • Do not inject into tattoos, moles, skin patches, bruises, rashes or areas where the skin is sensitive areas where the skin is sensitive, red, hard, bruised, damaged, burned or inflamed
  • Do not administer intramuscularly or intravenously

Re-start therapy after a pause due to severe thrombocytopenia
 

Low platelet counts were reversible if well managed with dose adjustments. 

It was not associated with any major or severe bleeding events.5 Increased frequency of platelet monitoring (every 2 weeks in the APPROACH index study and weekly in the open label extension study) suggests that weekly to biweekly platelet monitoring, combined with dose reductions as necessary, may be sufficient to avoid severe bleeding events associated with platelet count reductions.

EAMS*: trend of platelets accords the previous exposure (two years) 
– additionally no severe decrease (< 50.000).6

*EAMS, Early Access to Medicines Scheme

What to monitor?
 

Platelet Monitoring

 

Quarterly monitoring1

 

  Method Effects of the results
Nephrotoxicity Urine strips–if positive, more comprehensive examination of kidney function

Discontinue treatment if:

  • proteinuria of ≥ 500 mg/24 hours
  • increase in serum creatinine ≥ 0.3 mg/dl (26.5 μmol/l), i.e. > ULN
  • creatinine clearance ≤ 30 ml/min/1.73m2, estimated according to the CKD-EPI equation
  • any clinical symptoms or signs of renal insufficiency
Hepatotoxicity Serum liver enzymes and bilirubin

Discontinue treatment if:

  • simple increase in ALT or AST > 8xULN
  • increase > 5xULN that lasts for ≥ 2 weeks
  • minor increases in ALT or AST associated with total bilirubin > 2xULN or INR > 1.5 are connected
  • any clinical symptoms or signs of hepatic insufficiency or hepatitis
Inflammations Erythocyte sedimentation rate (ESR) Reporting of an adverse reaction if the formation of antibodies against drugs with a clinically significant effect is suspected.

 

Abbreviations: ALT=alanine aminotransferase; AST=aspartate aminotransferase; CKD-EPI=Chronic Kidney Disease Epidemiology Collaboration; INR=increase in normalized coagulation value (INR-International Normalized Ratio); ULN=upper limit of normality

References

  1. Waylivra EMA Summary of Product Characteristics. November 2022
  2. Hegele RA et al. Rare dyslipidaemias, from phenotype to genotype to management: a European Atherosclerosis Society task force consensus statement Lancet Diabetes & Endocrinology. 8:50-67 (2020).
  3. Bashir B, et al. Severe Hypertriglyceridaemia and Chylomicronaemia Syndrome— Causes, Clinical Presentation, and Therapeutic Options. Metabolites. 2023; 13(5):621.
  4. Stroes E et al., Diagnostic algorithm for familial chylomicronemia syndrome, Atherosclerosis Supplements. 2017, 23:1–7.
  5. Witztum JL, et al. Journal of Clinical Lipidology 2023;17:342–355.
  6. Jones et al. Long-term effects of volanesorsen on triglycerides and pancreatitis in patients with familial chylomicronaemia syndrome (FCS) in the UK Early Access to Medicines Scheme (EAMS). Atherosclerosis 375 (2023) 67–74.