Loargys (Pegzilarginase)

What Is Loargys and What Is It Used For?

Loargys (pegzilarginase) is an enzyme replacement therapy used to treat arginase 1 deficiency (ARG1-D), also known as hyperargininemia. It is approved for adults, adolescents and children aged 2 years and older. Loargys works by replacing the missing arginase enzyme, lowering dangerous arginine levels in the blood.

Arginase 1 deficiency is a rare inherited metabolic disorder that belongs to the group of urea cycle disorders. In healthy individuals, the enzyme arginase 1 plays a critical role in the urea cycle – the metabolic pathway by which the body converts nitrogen waste (ammonia) into urea for excretion. Arginase specifically catalyses the final step of this cycle, converting the amino acid arginine into ornithine and urea. When arginase is deficient or dysfunctional, arginine accumulates to abnormally high concentrations in the blood (hyperargininemia), leading to progressive and potentially severe clinical consequences.

The accumulation of arginine is toxic to the central nervous system. Patients with ARG1-D typically develop progressive spasticity (difficulty controlling muscles, particularly in the legs), impaired motor function, intellectual disability, seizures, and growth retardation. These symptoms usually become apparent in early childhood and can progress over time if not adequately managed. Some patients may also develop elevated ammonia levels (hyperammonaemia), although this is generally less severe than in other urea cycle disorders.

Loargys contains the active substance pegzilarginase, which is a modified (PEGylated) form of human arginase 1 produced using recombinant DNA technology. The PEGylation process attaches polyethylene glycol (PEG) chains to the enzyme, which significantly extends its duration of action in the body, allowing for once-weekly dosing rather than the continuous enzymatic activity normally provided by the endogenous enzyme. By supplementing the deficient enzyme, Loargys reduces plasma arginine concentrations toward the normal range, thereby mitigating the toxic effects of arginine accumulation.

Loargys is not intended to replace existing supportive care. Instead, it is used in combination with other disease management strategies, which may include a low-protein diet to limit dietary arginine intake, supplementation with essential amino acids to prevent nutritional deficiency, and medications to lower blood ammonia levels (such as nitrogen-scavenging agents) when needed. The treating physician will develop an individualised management plan that integrates Loargys with these supportive measures to achieve optimal disease control.

Orphan Medicine Status

Loargys has been designated as an orphan medicine by the European Medicines Agency (EMA) because ARG1-D is an ultra-rare condition. It is estimated to affect approximately 1 in 300,000 to 1 in 1,000,000 live births worldwide. Due to the extreme rarity of the disease, it has not been possible to obtain complete clinical data, and the medicine was approved under “exceptional circumstances.” This means that the EMA reviews any new data that becomes available annually and updates the prescribing information as needed.

What Should You Know Before Taking Loargys?

Do not use Loargys if you have had a severe allergic reaction to pegzilarginase or any of its other ingredients. Allergic reactions can occur, especially after the first doses. Your doctor will monitor you during treatment and adjust the dose based on regular blood tests.

Contraindications

Loargys must not be used if you have previously had a severe allergic reaction (anaphylaxis or serious hypersensitivity reaction) to the active substance pegzilarginase or to any of the other ingredients in the solution. The other ingredients include sodium chloride, potassium dihydrogen phosphate, dipotassium phosphate, glycerol, hydrochloric acid, sodium hydroxide, and water for injections. If you are unsure whether you have had a reaction to any of these components, consult your doctor before starting treatment.

Warnings and Precautions

Allergic reactions (hypersensitivity) are one of the most important safety concerns with Loargys. These reactions are most likely to occur after the initial doses, but they can also develop later during the course of treatment. Symptoms of an allergic reaction may include hives (urticaria), generalised itching, chest tightness, difficulty breathing (dyspnoea), facial swelling, skin rash, or low blood pressure.

If you develop signs of a serious allergic reaction during administration, the infusion or injection should be stopped immediately and your doctor will provide appropriate medical treatment. Depending on the severity, your doctor may decide to adjust subsequent doses, pre-medicate you with antihistamines or corticosteroids before future administrations, or discontinue Loargys entirely.

During treatment, your doctor will perform regular blood tests to measure your plasma arginine levels. These tests are essential for determining the correct dose of Loargys. Too high a dose may lower arginine levels excessively, which can itself cause symptoms such as nausea, vomiting, diarrhoea, and fatigue. Your doctor will titrate the dose to maintain arginine levels within a safe and therapeutic range.

Use in Children

Loargys is approved for children aged 2 years and older. It has not been studied in children under 2 years of age, and its safety and efficacy in this age group have not been established. The dose is calculated based on body weight (mg per kg) and is the same for all age groups from 2 years upward. Children and adolescents receiving Loargys should have their growth, nutritional status, and neurological development monitored regularly by their treating physician.

Other Medicines and Loargys

Tell your doctor if you are taking, have recently taken, or might take any other medicines. While no formal drug interaction studies have been conducted with Loargys, it is important for your healthcare team to have a complete picture of all medications and supplements you are using to ensure safe and coordinated care. Since ARG1-D patients often take nitrogen-scavenging agents and amino acid supplements concurrently, your doctor will manage these therapies as a whole.

Pregnancy and Breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before receiving Loargys. The medicine is not recommended during pregnancy because there is insufficient data on its safety in pregnant women.

It is not known whether pegzilarginase passes into breast milk. If you are breastfeeding, your doctor will help you weigh the benefits of treatment against any potential risks to the infant and decide whether to discontinue breastfeeding or discontinue treatment.

Driving and Using Machines

Loargys has no or negligible effect on the ability to drive and use machines. There is no evidence that it causes drowsiness, dizziness, or any other impairment that would affect driving or the operation of machinery.

Sodium and Potassium Content

Loargys contains less than 1 mmol sodium (23 mg) per dose, meaning it is essentially “sodium-free.” It also contains less than 1 mmol potassium (39 mg) per dose, making it essentially “potassium-free.” This is relevant for patients on sodium-restricted or potassium-restricted diets.

How Does Loargys Interact with Other Drugs?

No formal drug interaction studies have been conducted with Loargys. Because pegzilarginase is a PEGylated enzyme (not a small-molecule drug), it is not expected to interact through common metabolic pathways such as cytochrome P450 enzymes. However, always inform your doctor of all medications and supplements you are taking.

Pegzilarginase is a large recombinant protein that functions as an enzyme substitute. Unlike small-molecule drugs, it is not metabolised by cytochrome P450 (CYP) enzymes in the liver, nor does it inhibit or induce CYP pathways. Therefore, traditional pharmacokinetic drug interactions are not anticipated. The PEGylated protein is instead cleared through proteolytic degradation and renal elimination of PEG fragments, pathways that are generally independent of the metabolic routes used by most conventional drugs.

That said, patients with arginase 1 deficiency commonly receive multiple concomitant therapies that require careful coordination. These may include:

It is particularly important to note that valproic acid (valproate), commonly used as an antiepileptic drug, carries a specific risk in patients with urea cycle disorders because it can inhibit the urea cycle and precipitate hyperammonaemic crises. If you have ARG1-D and are prescribed an antiepileptic drug, your doctor should be aware of this risk and may choose alternative antiepileptic agents.

Because Loargys reduces plasma arginine levels, there is a theoretical possibility that it could affect the efficacy or clearance of other therapies indirectly by altering the metabolic environment. For example, as arginine levels normalise, the need for nitrogen-scavenging agents may decrease. Your doctor will reassess all concomitant medications periodically and adjust dosing as needed based on clinical response and laboratory monitoring.

What Is the Correct Dosage of Loargys?

The recommended starting dose of Loargys is 0.1 mg per kg of body weight, administered once weekly. Your doctor may increase or decrease the dose based on your blood arginine levels. Loargys is given either as an intravenous infusion (over at least 30 minutes) or as a subcutaneous injection.

Loargys will initially be administered by a healthcare professional. Your doctor will determine the appropriate dose based on your body weight and will adjust the dose over time guided by regular blood tests that measure your plasma arginine concentration. The goal is to maintain arginine levels within a safe range that minimises disease symptoms while avoiding excessive arginine depletion.

Adults and Adolescents

Children (Aged 2 Years and Older)

Route of Administration

Loargys can be administered by two routes, depending on what your doctor considers most appropriate:

• Intravenous (IV) infusion: The solution is diluted with sodium chloride 0.9% to the desired volume (maximum pegzilarginase concentration of 0.5 mg/ml) and infused over at least 30 minutes. IV administration is typically performed in a healthcare setting. Do not mix Loargys with other medications or infuse other drugs through the same IV line simultaneously.
• Subcutaneous (SC) injection: The undiluted solution is injected under the skin in the abdomen, side of the thigh, or side/back of the upper arm. Rotate injection sites between doses. If the required dose exceeds 1 ml, it should be split into multiple injections at different sites, each at least 3 cm apart. After appropriate training from your doctor or nurse, you may self-administer subcutaneous injections at home.

Missed Dose

If you miss a dose, contact your doctor to arrange the next dose as soon as possible. Do not take a double dose to make up for the missed one. There must be at least 4 days between consecutive doses to avoid excessive arginine depletion.

Overdose

Stopping Loargys

Your doctor will decide whether and when to stop treatment with Loargys. If you discontinue the medicine, your plasma arginine levels are likely to rise again, potentially leading to a worsening of disease symptoms. Do not stop treatment on your own without consulting your doctor. If you have any questions about the duration of your treatment, discuss them with your healthcare team.

What Are the Side Effects of Loargys?

The most common side effects of Loargys are injection site reactions (pain, swelling, redness) and allergic reactions (hypersensitivity), both of which occur in more than 1 in 10 patients. Allergic reactions are most likely after the first doses but can occur at any time during treatment.

Like all medicines, Loargys can cause side effects, although not everybody gets them. Because ARG1-D is an ultra-rare disease and the clinical trial populations were small, the full side effect profile may not yet be completely characterised. Any new or unexpected symptoms should be reported to your doctor.

Because Loargys was approved under exceptional circumstances based on limited clinical data from a small patient population, the frequency categories above are based on the available evidence. It is possible that additional side effects may be identified as more patients are treated and the post-marketing safety database grows. The EMA reviews new safety data annually.

Managing Injection Site Reactions

Injection site reactions are among the most frequently reported side effects. These are generally mild to moderate and self-limiting, resolving within a few days. To minimise injection site discomfort, allow the vial to reach room temperature (15–30 minutes out of the refrigerator) before injection, rotate injection sites between each administration, and inject slowly. If reactions are persistent or bothersome, discuss them with your doctor, who may recommend topical measures or adjustments to the injection technique.

Managing Allergic Reactions

Your doctor may decide to pre-medicate you with antihistamines, corticosteroids, or other medications before your Loargys dose to reduce the risk of allergic reactions. If you have experienced an allergic reaction during a previous dose, do not skip subsequent doses without your doctor’s guidance – they will determine whether it is safe to continue with pre-medication or whether treatment should be discontinued.

Reporting Side Effects

It is important to report suspected side effects after the medicine has been authorised. This enables continuous monitoring of the benefit-risk balance. Healthcare professionals and patients are encouraged to report any suspected adverse reactions to their national medicines regulatory authority.

How Should You Store Loargys?

Store Loargys in a refrigerator at 2°C to 8°C. Do not freeze. Keep the vials in the original carton to protect from light. Once removed from the refrigerator, use within 2 hours at room temperature (up to 25°C). Each vial is for single use only.

Proper storage of Loargys is essential to maintain its efficacy and safety, as it is a biological medicine (a PEGylated recombinant enzyme) that is sensitive to temperature and light. Keep the medicine out of the sight and reach of children at all times.

• Refrigeration required: Store at 2°C to 8°C (36°F to 46°F). A standard household refrigerator set to its recommended temperature is suitable.
• Do not freeze: Freezing can damage the protein structure of the enzyme and render the medicine ineffective. If a vial has been accidentally frozen, do not use it – discard it and use a fresh vial.
• Protect from light: Keep the vials in the original carton at all times until ready for use.
• Room temperature use: Once removed from the refrigerator, Loargys can be stored at room temperature (up to 25°C / 77°F) for a maximum of 2 hours before administration. Do not return to the refrigerator after this period.
• Single use only: Each vial is intended for one-time use. Any remaining solution after the dose has been drawn up must be discarded. Do not save or re-use partially used vials.
• Prepared dose: If the solution is drawn into a syringe but not immediately administered, it may be stored protected from light at room temperature (up to 25°C) for up to 2 hours, or refrigerated (2°C to 8°C) for up to 4 hours. Discard if these time limits are exceeded.

Do not use this medicine after the expiry date printed on the vial label and carton (marked “EXP”). The expiry date refers to the last day of the stated month. Before use, visually inspect the solution: it should be colourless to slightly yellow or slightly pink, clear to slightly opalescent (pearlescent). Do not use if the solution is cloudy or contains visible particles.

Do not dispose of unused medicines via wastewater or household waste. Return any unused or expired vials to your pharmacy for safe disposal in accordance with local regulations.

What Does Loargys Contain?

Each vial of Loargys contains pegzilarginase at a concentration of 5 mg/ml. The solution is provided in single-use glass vials of 0.4 ml (2 mg) or 1 ml (5 mg). Inactive ingredients include sodium chloride, potassium dihydrogen phosphate, dipotassium phosphate, glycerol, and water for injections.

Active Ingredient

The active substance is pegzilarginase, a PEGylated recombinant human arginase 1 enzyme produced using recombinant DNA technology. Each 0.4 ml vial contains 2 mg of pegzilarginase and each 1 ml vial contains 5 mg of pegzilarginase, both at a concentration of 5 mg/ml.

Inactive Ingredients (Excipients)

The other ingredients are: sodium chloride, potassium dihydrogen phosphate, dipotassium phosphate, glycerol, hydrochloric acid (for pH adjustment), sodium hydroxide (for pH adjustment), and water for injections. These excipients serve as a buffer system and stabiliser to maintain the enzyme in its active conformation during storage.

Appearance and Packaging

Loargys is a colourless to slightly yellow or slightly pink, clear to slightly opalescent (pearlescent) liquid in a clear glass vial. Each carton contains 1 single-use vial of either 0.4 ml or 1 ml solution. Not all pack sizes may be available in all countries.

Marketing Authorisation Holder

Immedica Pharma AB, Stockholm, Sweden. This medicine was authorised in the European Union under exceptional circumstances, and the EMA reviews new information annually to update the product information as necessary.

How Does Loargys Work in the Body?

Loargys works by replacing the missing or dysfunctional arginase 1 enzyme in patients with ARG1-D. Pegzilarginase hydrolyses (breaks down) arginine into ornithine and urea, directly reducing dangerously elevated plasma arginine levels. The PEGylation extends the enzyme’s circulating half-life, enabling once-weekly dosing.

To understand how Loargys works, it is helpful to understand the underlying biochemistry of arginase 1 deficiency. The urea cycle is a series of enzymatic reactions that takes place primarily in the liver. Its function is to detoxify ammonia – a waste product of protein metabolism – by converting it into urea, which is then excreted by the kidneys. Arginase 1 catalyses the final step of the urea cycle: the hydrolysis of arginine to ornithine and urea.

In patients with ARG1-D, mutations in the ARG1 gene result in absent or severely reduced arginase 1 enzyme activity. This leads to the accumulation of arginine in the plasma and tissues. Arginine itself, and its downstream metabolites (such as guanidino compounds), are believed to be neurotoxic at elevated concentrations. The progressive neurological symptoms seen in ARG1-D – including spasticity, cognitive impairment, and seizures – are thought to result primarily from this arginine-mediated toxicity rather than from ammonia accumulation alone, which distinguishes ARG1-D from most other urea cycle disorders.

Pegzilarginase is a recombinant human arginase 1 enzyme that has been PEGylated – meaning that polyethylene glycol (PEG) molecules have been covalently attached to the enzyme protein. PEGylation is a well-established pharmaceutical modification that serves two important purposes:

• Extended half-life: The PEG chains shield the enzyme from rapid degradation by the body’s proteolytic enzymes and reduce renal clearance. This dramatically extends the circulating half-life compared to native (unmodified) arginase 1, allowing the therapeutic effect to be maintained with once-weekly dosing.
• Reduced immunogenicity: PEGylation can decrease the likelihood that the immune system will recognise and mount an immune response against the foreign protein, although allergic reactions can still occur (as noted in the side effects section).

Once administered (either intravenously or subcutaneously), pegzilarginase circulates in the bloodstream and systematically hydrolyses arginine to ornithine and urea, mimicking the metabolic function of the deficient endogenous enzyme. This results in a dose-dependent reduction of plasma arginine concentrations. The therapeutic goal is to lower arginine to levels that prevent or slow the progression of neurological damage while maintaining sufficient arginine for essential biological functions such as protein synthesis and immune function.

The dose of Loargys is individually titrated using regular plasma arginine monitoring. Because the PEGylated enzyme has a prolonged half-life, its effects build gradually over the dosing interval, and it typically takes several weeks of dose adjustment to achieve stable, well-controlled arginine levels. Once a stable dose is established, ongoing monitoring at regular intervals ensures that arginine levels remain within the target range.

Frequently Asked Questions About Loargys