Spevigo (Spesolimab)

What Is Spevigo and What Is It Used For?

Spevigo contains the active substance spesolimab, a humanized monoclonal antibody that belongs to a group of medicines known as interleukin (IL) inhibitors. Spesolimab works by specifically targeting and blocking the activity of a protein called the interleukin-36 receptor (IL-36R). This receptor plays a critical role in the inflammatory signaling cascade that underlies generalized pustular psoriasis. By binding to IL-36R, spesolimab prevents the inflammatory cytokines IL-36 alpha, IL-36 beta, and IL-36 gamma from activating the receptor and triggering the downstream inflammatory response.

Generalized pustular psoriasis (GPP) is a rare, severe, and potentially life-threatening form of psoriasis that is distinct from the more common plaque psoriasis. GPP is characterized by sudden, widespread episodes known as flares, during which painful, sterile, pus-filled blisters (pustules) appear rapidly across large areas of the skin. The surrounding skin becomes red, inflamed, and intensely tender. In addition to the dramatic skin manifestations, patients may experience systemic symptoms including high fever, extreme fatigue, headache, a burning sensation of the skin, and malaise. In severe cases, GPP flares can lead to serious complications such as secondary skin infections, sepsis, organ failure, and even death if not promptly and effectively managed.

The genetic basis of GPP involves mutations in genes affecting the IL-36 signaling pathway, most notably loss-of-function mutations in the IL36RN gene, which encodes the IL-36 receptor antagonist (IL-36Ra). When IL-36Ra is deficient or non-functional, unopposed IL-36 signaling drives the excessive neutrophilic inflammation characteristic of GPP. Spesolimab directly addresses this molecular mechanism by blocking IL-36R activation, thereby reducing pustule formation and the associated signs and symptoms of the disease.

Spevigo was initially approved in 2022 for the treatment of acute GPP flares as an intravenous infusion. The subcutaneous pre-filled syringe formulation was subsequently approved for the prevention of GPP flares, providing patients with a more convenient maintenance treatment option. Clinical trials, including the pivotal Effisayil 2 study, demonstrated that subcutaneous spesolimab significantly reduced the risk of GPP flares compared with placebo over a 48-week treatment period.

It is important to note that Spevigo specifically targets GPP and is not indicated for the treatment of plaque psoriasis or other forms of psoriasis. The distinction is clinically significant, as the pathophysiology of GPP differs fundamentally from that of plaque psoriasis, and treatments effective for one may not be effective for the other.

What Should You Know Before Taking Spevigo?

Before initiating treatment with Spevigo, a physician with experience in treating patients with inflammatory skin diseases should conduct a thorough evaluation. This includes screening for infections, reviewing vaccination history, and assessing any potential contraindications. The following information is essential for safe and effective use of this medicine.

Contraindications

You must not use Spevigo if you:

• Are allergic to spesolimab or any of the other ingredients in this medicine (sodium acetate trihydrate, concentrated acetic acid, sucrose, arginine hydrochloride, polysorbate 20, and water for injections).
• Have active tuberculosis (TB) or other severe, active infections. Spesolimab suppresses certain immune pathways and can increase the risk of infection progression. Tuberculosis screening, typically with a tuberculin skin test or interferon-gamma release assay, should be performed before starting treatment.

Warnings and Precautions

Speak with your doctor or nurse before and during use of Spevigo if you:

• Have an ongoing or recurring infection. Symptoms such as fever, flu-like symptoms, fatigue, shortness of breath, persistent cough, warm/red/painful skin, or painful blistering rash may indicate an infection that requires medical attention.
• Have or have had tuberculosis (TB), or have been in close contact with someone who has TB. Your doctor should test you for TB before you begin treatment.
• Have recently been vaccinated or plan to be vaccinated. You should not receive live vaccines for at least 16 weeks after receiving Spevigo. Your doctor will review your immunization status and administer any necessary vaccines before starting treatment. Inactivated vaccines may be given during treatment, but their effectiveness may be reduced.
• Experience symptoms of peripheral neuropathy, such as new weakness in your arms or legs, numbness, tingling, or a burning sensation in any part of your body. These symptoms may indicate nerve damage and should be reported promptly.

Infections

Spesolimab modulates immune signaling and may increase the risk of infections. In clinical trials, upper respiratory tract infections and urinary tract infections were among the most commonly reported adverse events. Patients should be educated about the signs and symptoms of infection and instructed to seek medical attention promptly if they occur. Healthcare providers should exercise caution when considering Spevigo in patients with a history of chronic or recurrent infections, and treatment should be interrupted if a serious infection develops.

Allergic Reactions

Allergic reactions, including delayed hypersensitivity reactions occurring 2-8 weeks after administration, have been reported with Spevigo. Symptoms may include difficulty breathing or swallowing, swelling of the face, lips, tongue, or throat, severe itching with red rash or raised bumps, or a feeling of faintness. Patients should seek immediate medical attention if they experience any of these symptoms. In addition, patients should be aware that widespread skin rash, fever, and facial swelling occurring weeks after treatment may indicate a delayed allergic reaction.

Drug Interactions

Inform your doctor about all medicines you are currently taking, have recently taken, or might take. Particular attention should be paid to:

• Live vaccines: Must not be administered for at least 16 weeks after Spevigo treatment. This includes vaccines for measles, mumps, rubella (MMR), varicella (chickenpox), oral polio, and yellow fever, among others.
• Other immunosuppressive therapies: The concurrent use of Spevigo with other immunosuppressive agents has not been extensively studied. Combination therapy may increase the risk of infections, and the decision to use Spevigo alongside other immunosuppressants should be made on an individual basis with careful risk-benefit assessment.
• CYP450 substrates: Chronic inflammation can alter the activity of cytochrome P450 enzymes. Since spesolimab reduces IL-36-driven inflammation, it could theoretically affect the metabolism of drugs processed by CYP450 enzymes. Patients on narrow therapeutic index drugs (e.g., warfarin, cyclosporine) should be monitored accordingly.

Pregnancy and Breastfeeding

Pregnancy: If you are pregnant, think you may be pregnant, or are planning to have a baby, seek advice from your doctor before using Spevigo. The effects of spesolimab on pregnancy outcomes in humans are unknown. As a precautionary measure, it is best to avoid the use of Spevigo during pregnancy. If you are pregnant, this medicine should only be used if your doctor has clearly recommended it after a thorough evaluation of the potential benefits versus risks.

Breastfeeding: It is not known whether spesolimab passes into human breast milk. As an IgG1 monoclonal antibody, spesolimab may pass into breast milk, particularly in the first days after childbirth. Patients who are breastfeeding or planning to breastfeed should discuss the decision with their healthcare provider to weigh the benefits of treatment against the potential risks to the nursing infant.

Children and Adolescents

Spevigo is approved for use in adolescents aged 12 years and older. It has not been studied in children under 12 years of age, and its use is not recommended in this age group. Dosing in adolescents is weight-based: those weighing 40 kg or more receive the standard adult dose, while those weighing 30 to less than 40 kg receive a reduced dose (see dosage section).

Driving and Operating Machinery

Spevigo is not expected to affect your ability to drive or use machines. No studies on the effects on driving or machine operation have been performed, but the pharmacological properties of spesolimab do not suggest any impairment of these abilities.

Important Information About Excipients

This medicine contains polysorbate 20 (0.4 mg per 1 mL pre-filled syringe), which may cause allergic reactions in some individuals. Tell your doctor if you have any known allergies to polysorbates. The medicine also contains less than 1 mmol (23 mg) sodium per dose and is therefore essentially sodium-free.

How Does Spevigo Interact with Other Drugs?

As a monoclonal antibody targeting the IL-36 receptor, spesolimab is not metabolized by cytochrome P450 enzymes and is therefore unlikely to cause direct pharmacokinetic drug-drug interactions. However, by modulating the immune system and reducing inflammation, spesolimab may indirectly affect the metabolism of concomitant medications. The following interactions should be considered:

Patients should always inform their healthcare provider of all prescription and over-the-counter medications, herbal supplements, and vitamins they are taking before starting Spevigo. This allows the treating physician to evaluate the potential for interactions and make appropriate adjustments to the treatment plan.

What Is the Correct Dosage of Spevigo?

Always use Spevigo exactly as your doctor or pharmacist has instructed. If you are unsure, check with your healthcare provider. Spevigo is administered by subcutaneous (under the skin) injection. The first dose should always be given by a healthcare professional. After proper training, patients or their caregivers may self-administer subsequent doses at home.

Adults and Adolescents (12+ years, weighing 40 kg or more)

Adolescents (12+ years, weighing 30 to less than 40 kg)

For adolescents weighing 30 to less than 40 kg, all doses should be administered by a healthcare professional (doctor or nurse) rather than self-injected at home.

How to Administer

Spevigo is injected under the skin (subcutaneously) in the upper thigh or the abdomen (at least 5 cm from the navel). The injection should not be given into areas that are tender, bruised, red, hard, or scarred. A different injection site should be used each time, at least 2 cm from the previous site. When multiple injections are needed for a single dose, each injection should be given at a separate site.

Before injection, remove the pre-filled syringe from the refrigerator and allow it to reach room temperature for 15 to 30 minutes. Do not speed up the warming process using microwaves or hot water. Inspect the solution before use: it should be clear to slightly shimmering, colorless to slightly brownish-yellow. Very small white or translucent particles are normal. Do not use the syringe if the solution is cloudy, contains flakes, or large or colored particles.

Missed Dose

If you forget to use Spevigo, inject a dose as soon as you remember. If you are unsure about what to do, contact your healthcare provider for guidance. Do not inject a double dose to make up for a missed dose. Try to return to your regular dosing schedule as soon as possible.

Overdose

If you have used more Spevigo than prescribed, or if the dose was taken earlier than directed, speak with your doctor. In clinical studies, doses higher than the recommended therapeutic dose have been administered without additional safety signals emerging. However, there is no specific antidote for spesolimab overdose, and management should be supportive and symptomatic under medical supervision.

Stopping Treatment

Do not stop using Spevigo without first speaking to your doctor. Discontinuing treatment may lead to the return of GPP symptoms or the occurrence of a flare. Your physician will work with you to determine the appropriate duration of treatment and will monitor your condition throughout.

What Are the Side Effects of Spevigo?

Like all medicines, Spevigo can cause side effects, although not everybody gets them. Most side effects are mild to moderate in severity and tend to decrease over time as the body adjusts to the medicine. However, some side effects can be serious and require prompt medical attention.

The following side effects have been reported with Spevigo, organized by frequency:

In clinical trials for the subcutaneous formulation, injection site reactions were the most frequently observed adverse events, occurring in a significant proportion of patients. These reactions were generally mild to moderate and did not lead to treatment discontinuation in most cases. The incidence of infections was higher with spesolimab compared to placebo, reflecting the immunomodulatory mechanism of the drug.

Long-term safety data from open-label extension studies have shown a consistent safety profile over treatment periods exceeding one year, with no new safety signals emerging. However, as with all biologic therapies, ongoing pharmacovigilance is essential, and patients should report any unusual or persistent symptoms to their healthcare provider.

Reporting Side Effects

Reporting suspected adverse reactions after the medicine has been authorized is important. It allows continued monitoring of the benefit-risk balance of the medicine. Healthcare professionals and patients are encouraged to report any suspected adverse reactions to their national regulatory authority (e.g., the EMA in Europe, the FDA in the United States, or the MHRA in the United Kingdom).

How Should You Store Spevigo?

Proper storage of Spevigo is essential to maintain the stability and efficacy of the medicine. Improper storage can lead to degradation of the active substance and may render the medicine ineffective or potentially harmful. The following storage guidelines should be strictly followed:

• Store in a refrigerator at 2 °C to 8 °C (36 °F to 46 °F).
• Do not freeze. If Spevigo has been frozen, even if subsequently thawed, do not use it and discard it properly.
• Room temperature storage: If necessary, Spevigo can be stored at temperatures up to 25 °C (77 °F) for a maximum of 14 days. Discard the medicine if it has been stored at room temperature for more than 14 days.
• Keep in the original packaging to protect the solution from light.
• Keep out of the sight and reach of children.
• Do not use after the expiry date (EXP) printed on the pre-filled syringe and carton. The expiry date refers to the last day of that month.
• Do not use if the solution is cloudy, contains flakes, or large or colored particles.

Used pre-filled syringes and needle shields should be placed in a sharps disposal container immediately after use. Do not dispose of pre-filled syringes in household waste. Ask your pharmacist how to dispose of medicines and sharps containers that are no longer needed. These measures help to protect the environment and prevent accidental needle-stick injuries.

What Does Spevigo Contain?

Understanding the composition of Spevigo is important for patients who have known allergies or sensitivities to specific excipients. Each pre-filled syringe contains:

Active Substance

• Spesolimab 150 mg in 1 mL solution – a humanized IgG1 monoclonal antibody produced by recombinant DNA technology in Chinese hamster ovary (CHO) cells.

Inactive Ingredients (Excipients)

• Sodium acetate trihydrate (E262) – buffer to maintain pH stability
• Concentrated acetic acid (E260) – for pH adjustment
• Sucrose – stabilizer to protect the antibody during storage
• Arginine hydrochloride – stabilizer to prevent aggregation
• Polysorbate 20 (E432) – surfactant to prevent protein aggregation (0.4 mg per syringe; may cause allergic reactions in susceptible individuals)
• Water for injections – solvent

Appearance and Packaging

Spevigo injection solution is a clear to slightly shimmering, colorless to slightly brownish-yellow liquid in a pre-filled syringe with a needle safety device. Very small white or translucent particles may be present and are normal. Each carton contains 2 pre-filled syringes. The needle retracts into the safety shield after injection to prevent accidental needle-stick injuries.

The marketing authorization holder is LEO Pharma A/S (Industriparken 55, DK-2750 Ballerup, Denmark), and the manufacturer is Boehringer Ingelheim Pharma GmbH & Co. KG (Birkendorfer Strasse 65, 88397 Biberach an der Riss, Germany).