About Waylivra

Waylivra is an antisense oligonucleotide designed to inhibit the translation of apoC-III (1)

About Waylivra

Waylivra is an antisense oligonucleotide designed to inhibit the translation of apoC-III (1)

Waylivra Mode of Action

By reducing ApoC-III*, Waylivra removes an inhibitor of triglyceride clearance, enabling triglyceride metabolism through an LPL-independent pathway in patients with FCS.1

* Apolipoprotein C-III (ApoC-III) modulates triglyceride levels primarily by inhibiting the LPL-dependent pathway but also the LPL-independent pathway.



Waylivra significantly reduced fasting triglycerides1

When added to diet, Waylivra delivered a 77 % mean reduction in fasting triglycerides at 3 months and maintained statically significant reductions for a full year.1

Waylivra led to a lower incidence of pancreatitis1,2

An analysis of patients with a history of recurrent pancreatitis events (≥ 2 events in the 5 years prior to Study Day 1) showed a significant reduction in pancreatitis attacks in Waylivra-treated patients compared to placebo-treated patients (p=0.0242).1

Pancreatitis attacks* during the 52-week study period:

  • in the Waylivra group: none of the 7 patients who had 24 pancreatitis attacks* in the 5 years prior to study enrollment, experienced an attack.
  • in the placebo group: 3 of the patients who had 17 pancreatitis attacks* in the prior 5 years.

The APPROACH trial was a phase 3, double-blind study that evaluated efficacy and safety of volanesorsen for familial chylomicronemia syndrome in adults with confirmed genetic mutations or low LPL activity and high fasting triglyceride levels. Participants underwent a diet stabilization phase before being randomized to receive weekly volanesorsen or placebo, with a primary endpoint of fasting triglyceride level change at 3 months. Conducted globally across 40 centers, the trial ensured ethical compliance and patient consent, with safety monitored through adverse event tracking. Data analysis was performed using an ANCOVA model, with a hierarchical approach to secondary endpoints and additional exploratory analyses for lipid changes.


Results support the long-term use of Waylivra in patients with FCS3

The OLE-study* evaluated long-term Waylivra treatment in 62 patients** with FCS and showed:

Sustained efficacy up to 156 weeks

Consistent safety profile up to 156 weeks with previously published studies

The results of the OLE-study support the long-term use of Waylivra in adult patients with genetically confirmed FCS at high risk for pancreatitis in conjunction with diet

* This study had some limitations, including those inherent with an open-label study design. Without a placebo or non-treatment group, assessing whether an actual reduction in acute pancreatitis risk occurred is challenging.

** Confirmation of FCS type I phenotype–based on disease history, PCR, or next-generation sequencing results.


Waylivra safety profile1

System organ class Very common reactions (≥1/10) Common reactions (≥1/100 to <1/10)
Blood and lymphatic system disorders Thrombocytopenia Leukopenia, lymphopenia, eosinophilia, immune thrombocytopenic purpura, spontaneous haematoma
Immune system disorders   Immunisation reaction, hypersensitivity, serum sickness-like reaction
Metabolism and nutrition disorders   Diabetes mellitus
Psychiatric disorders   Insomnia
Nervous system disorders Headache Syncope, hypoaesthesia, presyncope, retinal migraine, dizziness, tremor
Eye disorders   Conjunctival haemorrhage, vision blurred
Vascular disorders   Haematoma, hypertension, haemorrhage, hot flush
Respiratory, thoracic, and mediastinal disorders   Dyspnoea, pharyngeal oedema, wheezing, epistaxis, cough, nasal congestion
Gastrointestinal disorders   Nausea, diarrhoea, vomiting, abdominal distension, abdominal pain, dry mouth, gingival bleeding, mouth haemorrhage, parotid gland enlargement, dyspepsia, gingival swelling
Skin and subcutaneous tissue disorders   Erythema, pruritus, rash, urticaria, hyperhidrosis, petechiae, ecchymosis, night sweats, papule, skin hypertrophy, swelling face
Musculoskeletal and connective tissue disorders Myalgia Arthralgia, pain in extremity, arthritis, musculoskeletal pain, back pain, neck pain, pain in jaw, muscle spasms, joint stiffness, myositis, peripheral arthritis
Renal and urinary disorders   Haematuria, proteinuria
General disorders and administration site conditions Injection site erythema, injection site pain, injection site swelling, injection site discolouration, injection site induration, injection site pruritus, injection site bruising, chills, injection site oedema Injection site haematoma, asthenia, fatigue, injection site reaction, pyrexia, injection site hypoaesthesia, injection site haemorrhage, injection site warmth, injection site dryness, injection site pallor, injection site urticaria, injection site vesicles, malaise, feeling hot, influenza-like illness, injection site discomfort, injection site inflammation, injection site mass, oedema, pain, injection site paraesthesia, injection site scab, injection site papule, injection site rash, non-cardiac chest pain, vessel puncture site haemorrhage
Investigations Platelet count decreased Haemoglobin decreased, white blood cell count decreased, blood creatinine increased, blood urea increased, creatinine renal clearance decreased, hepatic enzyme increased, international normalised ratio increased, transaminases increased
Injury, poisoning, and procedural complications   Contusion


The most common adverse reactions reported in the APPROACH trial were injection-site reactions and decreased platelet count including thrombocytopenia.2


  • Hypersensitivity to the active substance or to any of the excipients.
  • Chronic or unexplained thrombocytopenia. Treatment should not be initiated in patients with thrombocytopenia (platelet count <140 x 109/L).

Please refer to Waylivra summary of product characteristics for further safety information.

Platelet monitoring

Platelet monitoring is necessary during treatment1


  • Prior to initiation of Waylivra, patients should have a platelet count ≥140 × 109/L
  • During treatment, platelet levels should be monitored at least every 2 weeks and dosing and frequency of monitoring modified according to the table below


Platelet count (× 109/L) Dose (285 mg prefilled syringe) Monitoring frequency
Normal ≥140 Starting dose: Weekly.
After 3 months: Every 2 weeks
Every 2 weeks
100 to 139 Every 2 weeks Weekly
75 to 99 Pause treatment for ≥4 weeks and resume treatment after platelet levels ≥100 x 109/L Weekly
50 to 74a Pause treatment for ≥4 weeks and resume treatment after platelet levels ≥100 × 109/L Every 2-3 days
<50a,b Discontinue treatment. Glucocorticoids recommended  


a. Discontinuation of antiplatelet medicinal products/NSAIDs/anticoagulants should be considered for platelet levels <75 × 109/L. Treatment with these medicinal products must be discontinued at platelet levels <50 × 109/L.1
b. Consultation of a haematologist is needed to reconsider the benefit/risk for possible further treatment with Waylivra in a patient who has discontinued due to severe thrombocyotpenia (<50 x 109/L).1

Please refer to Waylivra summary of product characteristics for further safety information.


  1. Waylivra EMA Summary of Product Characteristics. November 2022
  2. Witztum JL et al. Volanesorsen and Triglyceride Levels in Familial Chylomicronemia Syndrome. N Engl J Med. 2019 Aug 8;381(6):531-542. doi: 10.1056/NEJMoa1715944. PMID: 31390500.
  3. Witzum JL et al., Journal of Clinical Lipidology (2023) 000, 1–14 Published: March 21, 2023. DOI:https://doi.org/10.1016/j.jacl.2023.03.007