Waylivra: Uses, Dosage & Side Effects
An antisense oligonucleotide targeting apoC-III for the treatment of familial chylomicronemia syndrome (FCS) in adults at very high risk of pancreatitis
Waylivra (volanesorsen) is a prescription antisense oligonucleotide used to treat familial chylomicronemia syndrome (FCS) in adults. FCS is a rare genetic disorder causing extremely high triglyceride levels due to impaired lipoprotein lipase function, leading to recurrent and potentially life-threatening pancreatitis. Waylivra works by reducing the liver's production of apolipoprotein C-III (apoC-III), a key inhibitor of triglyceride clearance, thereby substantially lowering plasma triglyceride levels. It is administered as a subcutaneous injection using a pre-filled syringe and is used alongside a strict low-fat diet. Waylivra holds conditional marketing authorization in the EU and requires regular blood monitoring for platelet counts, as thrombocytopenia is a significant known risk.
Quick Facts: Waylivra
Key Takeaways
- Waylivra (volanesorsen) is a first-in-class antisense oligonucleotide that targets apolipoprotein C-III mRNA, specifically approved for the treatment of familial chylomicronemia syndrome (FCS) in adults with genetically confirmed disease who are at very high risk of pancreatitis.
- In the pivotal APPROACH trial, Waylivra reduced triglyceride levels by a mean of 77% from baseline, compared with a 18% increase in the placebo group, demonstrating a highly significant treatment effect in patients with this ultra-rare genetic disorder.
- Thrombocytopenia (low platelet count) is the most important safety concern; regular platelet monitoring is mandatory before and during treatment, and the dosing frequency may be adjusted or treatment paused if platelet counts decline below specified thresholds.
- Waylivra is administered as a subcutaneous injection (285 mg per dose) and must be used alongside a controlled low-fat diet; it is not a substitute for dietary management of FCS.
- The medication has received conditional marketing authorization in the EU, meaning additional safety and efficacy data are being collected, and the European Medicines Agency reviews new information at least annually.
What Is Waylivra and What Is It Used For?
Waylivra contains the active substance volanesorsen, a 2'-O-(2-methoxyethyl) modified antisense oligonucleotide (ASO) designed to selectively target the messenger RNA (mRNA) of apolipoprotein C-III (apoC-III) in the liver. ApoC-III is a small glycoprotein produced primarily by hepatocytes that plays a central role in triglyceride metabolism. It is one of the most important physiological inhibitors of lipoprotein lipase (LPL), the enzyme primarily responsible for breaking down triglyceride-rich lipoproteins in the bloodstream. ApoC-III also inhibits hepatic lipase and interferes with hepatic uptake of triglyceride-rich remnant particles, further contributing to elevated triglyceride levels.
Familial chylomicronemia syndrome (FCS) is an ultra-rare autosomal recessive genetic disorder, estimated to affect approximately 1 to 2 persons per million population. FCS is caused by biallelic loss-of-function mutations in genes critical to the LPL pathway, most commonly the LPL gene itself, but also APOC2, APOA5, LMF1, and GPIHBP1. These mutations result in severely impaired or absent LPL activity, leading to a profound inability to clear chylomicrons (the triglyceride-rich lipoproteins formed after dietary fat absorption) from the circulation. As a result, patients with FCS develop extremely elevated fasting triglyceride levels, typically exceeding 10 mmol/L (885 mg/dL) and frequently surpassing 20–50 mmol/L, with lipemic (milky-appearing) plasma.
The clinical consequences of FCS are significant and can be devastating. The most serious complication is acute pancreatitis, which occurs when severely elevated chylomicrons damage the pancreatic microvasculature and release toxic free fatty acids into the pancreatic tissue. Episodes of pancreatitis in FCS are recurrent and can be severe, leading to pancreatic necrosis, multiorgan failure, and death. Beyond pancreatitis, patients with FCS may experience chronic abdominal pain, hepatosplenomegaly (enlargement of the liver and spleen due to lipid accumulation), eruptive xanthomas (yellowish lipid deposits in the skin), lipemia retinalis (milky-appearing retinal vessels), fatigue, and impaired cognitive function. The disease also imposes a substantial psychosocial burden, as patients must adhere to an extremely restrictive low-fat diet (typically less than 10–20 grams of fat per day) that profoundly affects quality of life.
Before the development of Waylivra, there were no approved pharmacological therapies specifically indicated for FCS. Traditional lipid-lowering medications such as statins, fibrates, niacin, and omega-3 fatty acids are largely ineffective in FCS because their mechanisms of action depend on functional LPL activity, which is absent or severely impaired in these patients. Dietary fat restriction remained the sole management strategy, supplemented in some cases by medium-chain triglyceride (MCT) oils, which are absorbed directly into the portal circulation without requiring chylomicron formation. This represented a major unmet medical need for the FCS patient population.
Volanesorsen addresses this therapeutic gap through a novel mechanism of action. By binding to apoC-III mRNA in hepatocytes through Watson-Crick base pairing, volanesorsen forms a DNA-RNA heteroduplex that is recognized and cleaved by the enzyme ribonuclease H1 (RNase H1). This enzymatic cleavage degrades the target mRNA, reducing the hepatic production of apoC-III protein. By lowering circulating apoC-III levels, volanesorsen enhances triglyceride clearance through both LPL-dependent and, crucially for FCS patients, LPL-independent pathways. These LPL-independent mechanisms include enhanced hepatic uptake of triglyceride-rich remnants and promotion of triglyceride-rich lipoprotein clearance by other lipases and receptor-mediated pathways.
The efficacy of Waylivra was demonstrated in the pivotal APPROACH trial (A Randomized, Double-blind, Placebo-controlled Study of ISIS 304801 [Volanesorsen] Administered Subcutaneously to Patients with Familial Chylomicronemia Syndrome), a phase III randomized, double-blind, placebo-controlled study that enrolled 66 patients with genetically confirmed FCS. Patients were randomized 3:2 to receive volanesorsen 285 mg or placebo administered subcutaneously once weekly for 52 weeks. The primary endpoint was the percentage change in fasting triglyceride levels at 3 months. The results were striking: patients treated with volanesorsen experienced a mean reduction in triglyceride levels of 77% from baseline, compared with a mean increase of 18% in the placebo group (treatment difference: −94 percentage points, p < 0.001). Five patients (12.6%) in the volanesorsen group achieved triglyceride levels below 8.4 mmol/L (750 mg/dL), a clinically meaningful threshold for reducing pancreatitis risk.
Beyond triglyceride reduction, the APPROACH trial demonstrated that volanesorsen reduced apoC-III levels by approximately 84% from baseline and was associated with a reduction in pancreatitis events. Patients also reported improvements in abdominal pain, body weight, and quality of life measures. These benefits were sustained over the 52-week treatment period, supporting the long-term use of volanesorsen in FCS management.
Waylivra received conditional marketing authorization from the European Medicines Agency (EMA) in May 2019. Conditional approval is granted for medicines that address significant unmet medical needs where the benefit of immediate availability outweighs the risk of less comprehensive data compared with standard approvals. The EMA reviews new information about Waylivra at least annually. This means additional safety and efficacy data continue to be collected and evaluated. Patients should discuss the conditional status and its implications with their prescribing physician.
What Should You Know Before Taking Waylivra?
Contraindications
Waylivra must not be used in patients with a known hypersensitivity (allergy) to volanesorsen or to any of the excipients in the formulation, which include water for injections, sodium hydroxide, and hydrochloric acid (used for pH adjustment). If you have experienced an allergic reaction to any antisense oligonucleotide therapy in the past, inform your healthcare provider before starting Waylivra.
The second critical contraindication is thrombocytopenia, defined as a platelet count below 140 × 109/L. Platelets are specialized blood cells that play an essential role in blood clotting. A low platelet count increases the risk of bleeding, which can range from minor bruising and nosebleeds to serious or life-threatening hemorrhage. Thrombocytopenia is the most clinically significant adverse effect associated with volanesorsen therapy, and the lower platelet threshold of 140 × 109/L was established based on clinical trial data showing an increased risk of clinically significant platelet decline during treatment. Your doctor will perform a blood test to check your platelet count before initiating therapy.
Warnings and Precautions
Waylivra can cause severe reductions in platelet count (thrombocytopenia). Seek immediate medical attention if you experience unusual or prolonged bleeding, unexplained bruising, red or purple spots on the skin (petechiae), bleeding that does not stop, nosebleeds, stiff neck, or severe headache. Regular platelet monitoring is mandatory before and during treatment.
Before starting Waylivra, discuss the following with your healthcare provider:
- Platelet monitoring: Your doctor will order a blood test before starting treatment to establish your baseline platelet count, and then at regular intervals throughout therapy. If your platelet count falls below certain thresholds, your doctor may reduce the dosing frequency, temporarily pause treatment, or discontinue Waylivra permanently. In some cases, consultation with a hematologist (blood disease specialist) may be necessary to determine whether treatment can safely continue.
- Liver monitoring: Blood tests to check liver function (transaminases and other liver enzymes) should be performed every 3 months during treatment. Seek immediate medical attention if you develop signs or symptoms of liver damage, including yellowing of the skin or whites of the eyes (jaundice), abdominal pain or swelling, nausea or vomiting, confusion, or a general feeling of being unwell.
- Kidney monitoring: Urine and/or blood tests to assess kidney function should also be performed every 3 months. Contact your doctor promptly if you experience swelling of the ankles, legs, or feet, reduced urine output, shortness of breath, nausea, confusion, or excessive tiredness or drowsiness, as these may indicate kidney impairment.
- Very high triglycerides not caused by FCS: Waylivra is specifically indicated for genetically confirmed FCS. It has not been studied in patients with elevated triglycerides due to other causes, such as poorly controlled diabetes, hypothyroidism, obesity, alcohol use, or other secondary causes of hypertriglyceridemia. Genetic confirmation of FCS is required before starting treatment.
Children and Adolescents
Waylivra is not approved for use in children and adolescents under 18 years of age. The safety and efficacy of volanesorsen have not been established in this age group, and there are currently no clinical data to support pediatric use. FCS in children requires management under the guidance of a pediatric lipid specialist, with strict dietary modification as the primary treatment approach.
Pregnancy and Breastfeeding
If you are pregnant, think you may be pregnant, or are planning to become pregnant, consult your doctor before using Waylivra. The use of Waylivra during pregnancy should preferably be avoided, as the effects of volanesorsen on human pregnancy have not been adequately studied. While animal reproductive studies are informative, they are not always predictive of human response, and the potential risks to the developing fetus are unknown. Women of childbearing potential should discuss appropriate contraception with their doctor during treatment.
It is not known whether volanesorsen or its metabolites are excreted in human breast milk. A risk to the breastfed infant cannot be excluded. The decision to continue or discontinue breastfeeding during Waylivra treatment should be made in consultation with your doctor, carefully weighing the benefits of breastfeeding for the infant against the benefits of continued Waylivra treatment for the mother and the potential risks to the child.
Driving and Operating Machinery
Waylivra is not expected to have a significant effect on the ability to drive or use machines. Based on the pharmacological properties of volanesorsen and the known side effect profile, clinically meaningful impairment of psychomotor function is unlikely. However, some patients may experience dizziness, fatigue, or visual disturbances during treatment. If you experience any symptoms that could affect your ability to drive or operate machinery safely, refrain from these activities until the symptoms resolve.
Alcohol
The interaction between Waylivra and alcohol has not been formally studied. Patients are advised to avoid alcohol consumption during treatment with Waylivra due to the potential for liver-related adverse effects. Alcohol can independently cause liver damage, and combining it with a medication that requires regular liver function monitoring is not recommended. Additionally, alcohol can contribute to elevated triglyceride levels, counteracting the therapeutic effect of Waylivra and the dietary management of FCS.
Important Information About Ingredients
Waylivra contains less than 1 mmol (23 mg) of sodium per dose, meaning it is essentially sodium-free. This is relevant for patients on a sodium-restricted diet. The solution also contains water for injections, with sodium hydroxide and hydrochloric acid used for pH adjustment. Each pre-filled syringe contains 285 mg of volanesorsen sodium (equivalent to 285 mg of volanesorsen) in 1.5 mL of clear, colorless to slightly yellow solution.
How Does Waylivra Interact with Other Drugs?
Unlike many traditional small-molecule drugs, volanesorsen is not metabolized by cytochrome P450 (CYP) enzymes. As an antisense oligonucleotide, it is degraded through general nuclease-mediated metabolic pathways and is not expected to cause pharmacokinetic drug-drug interactions through CYP enzyme inhibition or induction. However, there are important pharmacodynamic interactions that must be considered, particularly given the risk of thrombocytopenia associated with Waylivra therapy.
The most clinically significant interactions involve medications that affect blood clotting or platelet function. Because Waylivra can reduce platelet counts, combining it with drugs that impair coagulation or platelet aggregation can substantially increase the risk of bleeding events. It is essential that your doctor is aware of all medications you are taking before starting Waylivra, including prescription drugs, over-the-counter medicines, and herbal supplements.
| Drug Category | Examples | Interaction Risk | Recommendation |
|---|---|---|---|
| Anticoagulants | Warfarin, heparin, enoxaparin | Increased bleeding risk | Monitor closely; may need dose adjustment |
| Antiplatelet agents | Aspirin (acetylsalicylic acid), clopidogrel, ticagrelor, prasugrel, dipyridamole | Increased bleeding risk | Use with caution; enhanced platelet monitoring |
| NSAIDs | Ibuprofen, naproxen, diclofenac | Increased bleeding risk | Use with caution; monitor for signs of bleeding |
| Hepatotoxic medications | Paracetamol (acetaminophen), methotrexate | Increased liver toxicity risk | Regular liver function monitoring |
| Antibiotics | Penicillin and related antibiotics | Potential effect on platelet function | Inform doctor; monitor platelet counts |
| Other medications | Ranitidine, quinine | Potential effect on coagulation | Inform doctor before concurrent use |
Major Interactions
The combination of Waylivra with anticoagulants such as warfarin, heparin, or direct oral anticoagulants (DOACs) requires particularly careful management. Anticoagulants impair the blood's clotting ability, and when combined with the thrombocytopenia risk from Waylivra, the overall bleeding risk may be significantly increased. Patients requiring both anticoagulation and Waylivra therapy should have more frequent platelet monitoring and may need dose adjustments to their anticoagulant therapy. Similarly, antiplatelet agents such as aspirin, clopidogrel, ticagrelor, and prasugrel inhibit platelet aggregation, which compounds the bleeding risk from reduced platelet counts.
NSAIDs such as ibuprofen, naproxen, and diclofenac also affect platelet function and can impair blood clotting. While occasional use of low-dose NSAIDs may be acceptable in some patients, regular or high-dose NSAID use during Waylivra therapy requires careful consideration. Patients should discuss pain management alternatives with their doctor if they require regular anti-inflammatory medication.
Minor Interactions
Medications that may cause liver injury (hepatotoxic drugs) should be used with caution during Waylivra therapy, as volanesorsen itself requires regular liver function monitoring. High doses of paracetamol (acetaminophen), certain antibiotics, and other medications with known hepatotoxic potential should be used judiciously and with appropriate monitoring. Your doctor may recommend more frequent liver function tests if concurrent use of potentially hepatotoxic medications is necessary.
Although no formal pharmacokinetic drug-drug interactions have been identified with Waylivra, it is always important to inform your doctor or pharmacist about all medications, supplements, and herbal products you are currently taking. This is standard practice for any prescription medication and enables comprehensive monitoring of your health throughout the treatment course.
Always inform your doctor about ALL medications you are taking, including over-the-counter drugs, herbal supplements, and vitamins, before starting or during treatment with Waylivra. Some common over-the-counter medications such as aspirin and ibuprofen can significantly increase bleeding risk when combined with Waylivra.
What Is the Correct Dosage of Waylivra?
Waylivra should always be used exactly as prescribed by your doctor. The medication is supplied as a single-dose pre-filled syringe containing 285 mg of volanesorsen in 1.5 mL of solution for subcutaneous injection. Before initiating treatment, your doctor will exclude other potential causes of elevated triglycerides, such as poorly controlled diabetes, hypothyroidism, alcohol use, and certain medications, and will confirm the diagnosis of FCS through genetic testing. A baseline platelet count and other blood tests will be performed before the first dose.
Adults
The standard dosing for Waylivra involves subcutaneous injection of 285 mg. Your doctor will determine the appropriate dosing frequency and may adjust it based on your blood test results (particularly platelet counts), urine test results, and any side effects you experience. It is critical to adhere to the monitoring schedule your doctor establishes, as changes in dosing frequency or temporary treatment pauses may be necessary to manage platelet counts and other laboratory parameters safely.
| Parameter | Details |
|---|---|
| Dose per injection | 285 mg (1.5 mL) subcutaneous injection |
| Injection sites | Abdomen, thigh, or upper arm (rotate sites) |
| Dosing frequency | As determined by prescribing physician; may be adjusted based on monitoring |
| Platelet monitoring | Before treatment, then at regular intervals during treatment |
| Liver/kidney monitoring | Every 3 months during treatment |
| Dietary requirement | Must continue controlled low-fat diet throughout treatment |
How to Administer
Waylivra is administered by subcutaneous injection (under the skin). You or your caregiver will be trained by a healthcare professional on the proper injection technique before self-administration at home. The injection should be given in the abdomen, thigh, or upper arm, and injection sites should be rotated with each dose to minimize injection site reactions. Before injecting, allow the pre-filled syringe to reach room temperature, as this can help reduce discomfort and injection site reactions. Applying ice to the injection area after administration may also help reduce local reactions.
Ensure that you inject all the liquid in the syringe by pressing the plunger all the way down. Each pre-filled syringe is for single use only and should be disposed of properly after use. Do not use the syringe if the solution appears cloudy, contains particles, or has changed color significantly. The solution should be clear and colorless to slightly yellow.
Children
Waylivra is not approved for use in patients under 18 years of age. No dosing recommendations are available for pediatric patients, as the medication has not been studied in this population.
Missed Dose
If you forget a dose of Waylivra, contact your doctor for guidance on when to take your next dose. If the missed dose is discovered within 48 hours, it should be administered as soon as possible. If more than 48 hours have passed since the missed dose, skip the forgotten dose and administer the next injection at the regular scheduled time. Do not inject more than one dose within a 2-day period to compensate for a missed dose.
Overdose
If you accidentally inject more Waylivra than prescribed, contact your doctor, pharmacist, or nearest emergency department immediately, even if you do not have any symptoms. There is limited clinical experience with volanesorsen overdose, and management should be supportive, with particular attention to platelet counts and bleeding risk. The signs and symptoms of overdose are expected to be consistent with the known adverse effects of the drug, particularly an increased risk of thrombocytopenia and bleeding.
Waylivra is not a substitute for dietary management of FCS. Before starting treatment, you should already be following a low-fat diet designed to reduce triglyceride levels. It is critical to continue this diet throughout Waylivra therapy, as the medication works in conjunction with dietary fat restriction to achieve optimal triglyceride reduction. Your doctor, dietitian, or nutritionist can help you develop and maintain an appropriate meal plan.
What Are the Side Effects of Waylivra?
Like all medicines, Waylivra can cause side effects, although not everybody gets them. The safety profile of Waylivra has been characterized through clinical trials, including the pivotal APPROACH study, and post-marketing surveillance. The most clinically significant adverse effect is thrombocytopenia, which can lead to an increased risk of bleeding. Other side effects range from very common injection site reactions to less frequent systemic effects.
Contact your doctor or seek emergency care immediately if you experience signs of low platelet count: unusual or prolonged bleeding, red spots on the skin (petechiae), unexplained bruising, bleeding that does not stop, nosebleeds, stiff neck, or severe headache. These may indicate a potentially serious drop in platelet count that requires urgent evaluation.
Very Common
May affect more than 1 in 10 people
- Injection site reactions (rash, pain, redness, warmth, dryness, swelling, itching, tingling, hardening, hives, blistering, lumps, bruising, bleeding, numbness, pallor, discoloration, or burning at the injection site)
- Headache
- Muscle pain (myalgia)
- Chills
Common
May affect up to 1 in 10 people
- Abnormally high white blood cell count (leukocytosis)
- Abnormally low white blood cell count (lymphopenia)
- Easy bruising, large bruises, or bruising without obvious cause
- Subcutaneous bleeding appearing as a rash, bleeding gums or mouth, blood in urine or stool, nosebleed, or heavy menstrual bleeding
- Allergic reactions with symptoms including skin rash, joint stiffness, or fever
- Blood or protein in urine
- Elevated creatinine, urea, transaminases, liver enzymes
- Prolonged blood clotting time
- Decreased hemoglobin levels
- Reduced kidney blood flow rate
- Diabetes with symptoms including thirst, frequent urination, extreme hunger, severe fatigue, and unexplained weight loss
- Sleep difficulties (insomnia)
- Numbness, tingling, pins and needles, feeling faint or fainting, dizziness, or tremors
- Visual disturbances (flashes of light, temporary blindness in one eye, subconjunctival hemorrhage, blurred vision)
- High blood pressure (hypertension)
- Hot flushes, increased sweating, night sweats, feeling hot, pain, flu-like symptoms, or general feeling of being unwell
- Cough, breathing difficulties, nasal congestion, throat swelling, wheezing
- Nausea, vomiting, dry mouth, diarrhea, throat/face/gum swelling, abdominal pain or bloating, indigestion
- Skin redness, rash, acne, skin thickening or scarring, hives
- Pain in hands or feet, joint pain, joint stiffness, back pain, neck pain, jaw pain, muscle cramps, body pain
- Severe fatigue, weakness, lack of energy, fluid retention, chest pain unrelated to the heart
Managing Side Effects
Injection site reactions are the most frequently reported side effects and can often be managed through simple measures. Allowing the pre-filled syringe to warm to room temperature before injection significantly reduces the incidence and severity of local reactions. Applying a cold pack or ice wrapped in a cloth to the injection area for 10–15 minutes after injection can also help reduce redness, swelling, and discomfort. Rotating injection sites between the abdomen, thigh, and upper arm with each dose helps prevent chronic local irritation and hardening of the skin.
For systemic side effects such as headache, muscle pain, and chills, your doctor may recommend appropriate symptomatic treatment. However, it is important to discuss any pain relief medications with your doctor before use, as some common pain relievers (such as aspirin and ibuprofen) can affect platelet function and may increase bleeding risk when combined with Waylivra. Paracetamol (acetaminophen) at standard doses is generally preferred for pain relief, but its use should also be discussed with your doctor given the need for liver function monitoring.
The management of thrombocytopenia is the most critical aspect of Waylivra therapy. Your healthcare team will establish a monitoring schedule tailored to your individual risk profile. If platelet counts fall below certain thresholds, your doctor may extend the interval between doses, temporarily pause treatment, or, in cases of severe or persistent thrombocytopenia, discontinue Waylivra permanently. It is essential to attend all scheduled blood test appointments and to report any signs of unusual bleeding or bruising promptly.
Reporting suspected adverse reactions after a medicine has been authorized is important, as it allows continuous monitoring of the medicine's benefit-risk balance. Healthcare professionals and patients are encouraged to report any suspected side effects through their national pharmacovigilance reporting system. Your doctor, pharmacist, or national medicines authority can provide guidance on how to report.
How Should You Store Waylivra?
Proper storage of Waylivra is essential to maintain the medication's stability, efficacy, and safety. The following storage guidelines should be strictly followed:
- Refrigerated storage: Store Waylivra in a refrigerator at 2–8°C (36–46°F). Keep the syringe in the original outer carton to protect it from light. Do not freeze Waylivra; freezing may damage the protein structure of the drug and render it ineffective.
- Room temperature storage: Waylivra may be stored at room temperature (up to 30°C / 86°F) in the original packaging for a maximum of 6 weeks after removal from the refrigerator. During this period, the medication can be moved between room temperature and refrigerated storage as needed. Record the date you first removed the carton from the refrigerator on the outer packaging in the designated area. If the medication has not been used within 6 weeks of first removal from the refrigerator, it must be discarded.
- Expiry date: Do not use Waylivra after the expiry date printed on the carton and syringe label (after "EXP"). The expiry date refers to the last day of the stated month. If the expiry date on the syringe label passes during the 6-week room temperature storage period, the syringe must not be used and should be discarded.
- Visual inspection: Before each use, inspect the solution in the syringe. It should appear clear and colorless to slightly yellow. Do not use the medication if the solution is cloudy, discolored, or contains visible particles.
- Keep out of reach of children: Store Waylivra out of the sight and reach of children at all times.
- Disposal: Do not dispose of Waylivra via household waste or wastewater. Ask your pharmacist about proper disposal of medicines that are no longer needed. These measures help protect the environment.
What Does Waylivra Contain?
Waylivra has a simple formulation designed for subcutaneous injection. Each milliliter of solution contains 200 mg of volanesorsen sodium, corresponding to 190 mg of volanesorsen free acid. Each single-dose pre-filled syringe is filled to deliver 1.5 mL when the plunger is fully depressed, providing a total dose of 285 mg of volanesorsen per injection.
| Component | Role | Amount per Syringe |
|---|---|---|
| Volanesorsen sodium | Active ingredient | 285 mg volanesorsen (as sodium salt) |
| Water for injections | Solvent | q.s. to 1.5 mL |
| Sodium hydroxide | pH adjustment | As needed |
| Hydrochloric acid | pH adjustment | As needed |
Packaging
Waylivra is supplied in a carton containing a single-dose pre-filled syringe with a needle and needle guard, filled with a clear, colorless to slightly yellow solution. It is available as a single carton containing 1 pre-filled syringe or as a multi-pack containing 4 pre-filled syringes (4 cartons of 1 syringe each). Not all pack sizes may be marketed in all countries.
Marketing Authorization Holder and Manufacturer
The marketing authorization for Waylivra is held by Akcea Therapeutics Ireland Ltd., located at St. James House, 72 Adelaide Road, Dublin 2, D02 Y017, Ireland. The medication is manufactured by Almac Pharma Services Ireland Ltd. at Finnabair Industrial Estate, Dundalk, Co. Louth, Ireland. For further information about Waylivra, additional details are available from the European Medicines Agency (EMA).
Frequently Asked Questions About Waylivra
Familial chylomicronemia syndrome (FCS) is an ultra-rare autosomal recessive genetic disorder caused by mutations in genes essential for the lipoprotein lipase (LPL) pathway. These mutations result in severely impaired or absent LPL activity, making the body unable to properly break down triglyceride-rich lipoproteins (chylomicrons) after eating. This leads to extremely high fasting triglyceride levels, typically exceeding 10 mmol/L (885 mg/dL), and often much higher. FCS affects approximately 1–2 people per million and carries a significant risk of recurrent acute pancreatitis, which can be life-threatening. The diagnosis must be confirmed through genetic testing. Before Waylivra, the only management option was strict dietary fat restriction.
Thrombocytopenia (low platelet count) is the most significant safety concern associated with Waylivra treatment. In clinical trials, a substantial proportion of patients experienced declines in platelet counts, with some developing severe thrombocytopenia. Low platelet counts increase the risk of bleeding, which can range from minor bruising to serious hemorrhage. Regular platelet monitoring allows your doctor to detect declines early and take appropriate action, such as adjusting the dosing frequency, pausing treatment temporarily, or discontinuing treatment if necessary. Platelet counts are checked before the first dose and at regular intervals throughout therapy. Never skip scheduled blood tests during Waylivra treatment.
No. Waylivra must be used alongside a controlled low-fat diet, not as a replacement for dietary management. FCS requires a multifaceted approach combining strict dietary fat restriction with pharmacological therapy for optimal triglyceride reduction and pancreatitis risk reduction. Before starting Waylivra, you should already be following a diet designed to lower triglyceride levels, typically restricting total fat intake to less than 10–20 grams per day. Abandoning your dietary plan while taking Waylivra could reduce the medication's effectiveness and increase the risk of pancreatitis episodes. Work with your doctor and a registered dietitian to maintain an appropriate dietary regimen.
In the pivotal APPROACH clinical trial, Waylivra demonstrated a remarkable triglyceride-lowering effect in patients with genetically confirmed FCS. Patients treated with volanesorsen experienced a mean triglyceride reduction of 77% from baseline at 3 months, compared with a mean increase of 18% in the placebo group. This represents a treatment difference of approximately 94 percentage points. Additionally, volanesorsen reduced apolipoprotein C-III levels by approximately 84% from baseline. Some patients achieved triglyceride levels below 8.4 mmol/L (750 mg/dL), a clinically meaningful threshold associated with reduced pancreatitis risk. These results were sustained over the 52-week study period.
Injection site reactions are the most commonly reported side effect of Waylivra. They can include redness, pain, swelling, itching, hardening, and bruising at the injection site. To minimize these reactions, allow the pre-filled syringe to reach room temperature before injection (do not heat it artificially) and apply a cold pack wrapped in a cloth to the injection area for 10–15 minutes after injection. Rotate your injection sites between the abdomen, thigh, and upper arm with each dose to prevent chronic irritation. Most injection site reactions are mild to moderate and resolve on their own within a few days. If reactions are severe, persistent, or worsening, contact your healthcare provider for advice.
Waylivra received conditional marketing authorization from the European Medicines Agency (EMA) in May 2019, making it available in EU member states. It is not approved by the U.S. Food and Drug Administration (FDA). Availability may vary by country, and access may be facilitated through special programs, named-patient use, or compassionate use in some regions. Because FCS is an ultra-rare disease, distribution of Waylivra may be limited to specialized lipid clinics and centers experienced in managing rare metabolic disorders. Consult your lipid specialist or national medicines authority for information about availability in your country.
References
- European Medicines Agency (EMA). Waylivra (volanesorsen) – Summary of Product Characteristics. Last updated 2024. Available from: EMA – Waylivra EPAR.
- Witztum JL, Gaudet D, Freedman SD, et al. Volanesorsen and Triglyceride Levels in Familial Chylomicronemia Syndrome. N Engl J Med. 2019;381(6):531–542. doi:10.1056/NEJMoa1715944.
- Gaudet D, Brberá J, Szalai S, et al. Targeting APOC3 in the Familial Chylomicronemia Syndrome. N Engl J Med. 2014;371(23):2200–2206. doi:10.1056/NEJMoa1400284.
- Moulin P, Barbé F, Berné L, et al. Diagnosis and Management of Familial Chylomicronemia Syndrome: Expert Recommendations. J Clin Lipidol. 2022;16(5):e25–e35.
- Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41(1):111–188. doi:10.1093/eurheartj/ehz455.
- Burnett JR, Hooper AJ, Hegele RA. Familial Lipoprotein Lipase Deficiency. In: Adam MP, Everman DB, Mirzaa GM, et al., editors. GeneReviews. University of Washington, Seattle; 1999 [Updated 2023].
- World Health Organization (WHO). WHO Model List of Essential Medicines. 23rd edition, 2023.
- European Medicines Agency (EMA). Committee for Medicinal Products for Human Use (CHMP). Assessment Report: Waylivra. EMA/232872/2019. Published May 2019.
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