Vyvgart Hytrulo (efgartigimod alfa and hyaluronidase-qvfc) for myasthenia gravis
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What is Vyvgart Hytrulo for myasthenia gravis?
Vyvgart Hytrulo (efgartigimod alfa and hyaluronidase-qvfc) is an injection therapy approved in the U.S. for adults with generalized myasthenia gravis (gMG) who are positive for antibodies targeting the acetylcholine receptor (AChR) — the most common type of MG-causing antibody.
Developed by Argenx, the treatment is administered via a subcutaneous, or under-the-skin injection, and is designed to ease symptoms in people with gMG. This administration method is expected to be easier and more convenient than that of the company’s older formulation of efgartigimod alpha, known as Vyvgart — which is approved in the U.S. for the same indication but given via intravenous (into-the-vein) injections.
Vyvgart Hytrulo is a product combination of Vyvgart’s active substance and a recombinant, or man-made, version of the human hyaluronidase PH20 enzyme, which degrades certain proteins in the skin to facilitate the delivery and absorption of biologic therapies.
Therapy snapshot
| Brand Name: | Vyvgart Hytrulo |
| Chemical Name: | Efgartigimod alfa and hyaluronidase-qvfc |
| Usage: | Treatment of generalized myasthenia gravis |
| Administration: | Under-the-skin (subcutaneous) injection |
How does Vyvgart Hytrulo work?
Myasthenia gravis (MG) is a rare autoimmune disorder driven by self-reactive antibodies that mistakenly attack proteins involved in nerve-muscle communication, causing the disease’s typical symptoms of muscle weakness and fatigue.
In most cases, these self-reactive antibodies target AChR, a protein receptor that triggers muscle contraction upon binding to a signaling molecule called acetylcholine.
Most antibodies circulating in the bloodstream, including those driving MG, belong to a class of antibodies known as the IgG class. Over time, IgG antibodies are eventually broken down and recycled, but a protein called neonatal Fc receptor (FcRn) helps to stabilize IgG antibodies circulating in the bloodstream and prevent their destruction.
Similarly to Vyvgart, Vyvgart Hytrulo works by blocking FcRn, thereby increasing the rate at which IgG antibodies, such as the self-reactive ones driving MG, are broken down. By lowering the levels of MG-driving antibodies, the therapy is expected to ease disease symptoms.
Vyvgart Hytrulo was developed using a technology from Halozyme Therapeutics, called Enhanze, that facilitates the delivery of biologic therapies typically given by an into-the-vein infusion. It relies on the use of the company’s proprietary recombinant human hyaluronidase PH20 enzyme to break down a major component of skin tissue, facilitating the dispersion and absorption of medicines given via subcutaneous injection.
Who can take Vyvgart Hytrulo?
Vyvgart Hytrulo was approved by the U.S. Food and Drug Administration in June 2023 to treat adults with gMG who are positive for anti-AChR antibodies. The decision made it the first subcutaneous therapy to gain approval in the U.S. for gMG.
In November 2023, the therapy also has been approved for the same indication by regulatory authorities in Europe, where it is marketed as Vyvgart SC. The therapy also was approved in Japan in January 2024, where it is marketed as Vyvdura, for the treatment of adults with gMG who do not sufficiently respond to first-line treatment with steroids or nonsteroidal immunosuppressive therapies.
Who should not take Vyvgart Hytrulo?
There are no known contraindications for the use of Vyvgart Hytrulo. However, its administration should be delayed in patients with an active infection until that infection is resolved.
Vyvgart Hytrulo also has been associated with hypersensitivity reactions, including rash, swelling of the deeper layers of the skin, and shortness of breath. If such a reaction occurs, proper supportive measures should be instituted by healthcare professionals if needed, or the patient should seek medical attention.
How is Vyvgart Hytrulo administered?
Vyvgart Hytrulo is given via a subcutaneous injection that should be administered only by a trained healthcare professional. Administration takes approximately 30 to 90 seconds, or less than two minutes at its maximum, to complete.
The therapy’s recommended dose is 1,008 mg efgartigimod alfa and 11,200 units of hyaluronidase. It is supplied in single-dose vials containing 5.6 mL of a yellowish, clear to opalescent solution.
Patients initially receive a first treatment cycle consisting of weekly injections over a period of four weeks, or about one month. Additional treatment cycles of four weekly injections are then given based on a patient’s clinical response. The safety of initiating a new cycle sooner than 50 days from the start of the previous cycle has not been established.
If patients miss a planned dose, the therapy may be administered for up to three days after the scheduled date. If more than three days go by without dosing, the original schedule should be resumed until the treatment cycle is completed.
Vyvgart Hytrulo may decrease the effectiveness of vaccines. Thus, it’s recommended that patients receive all age-appropriate vaccinations before starting a new treatment cycle. Vaccination with live-attenuated or live vaccines is not recommended during treatment.
Vyvgart Hytrulo in clinical trials
The approval of Vyvgart Hytrulo in the U.S. was mainly supported by data from the Phase 3 ADAPT-SC clinical trial (NCT04735432), completed in 2021.
ADAPT-SC trial
ADAPT-SC compared the effects of Vyvgart Hytrulo with the traditional into-the-vein Vyvgart over 12 weeks, or about three months. The trial enrolled 110 adults with gMG in North America, Europe, and Japan. Participants were randomly assigned to receive either four weekly doses of Vyvgart Hytrulo (1,000 mg) or Vyvgart at 10 mg/kg.
The results showed that Vyvgart Hytrulo was as effective, or noninferior, to Vyvgart in its ability to lower total IgG antibody levels one week after the last dose (a mean drop of 66.4% vs. 62.2%). A similar observation was made regarding its ability to lower the levels of anti-AChR antibodies.
The subcutaneous formulation also lead to improvements in the MG Activities of Daily Living (MG-ADL) and Quantitative MG (QMG) scores that were consistent with those seen in the ADAPT trial (NCT03669588) of Vyvgart.
Specifically, 69.1% of patients treated with Vyvgart Hytrulo attained clinically meaningful improvements in the MG-ADL, a patient-reported measure of disease severity, and 65.5% had meaningful improvements in QMG, a measure of MG severity as reported by clinicians. The safety profile of the two treatments also was similar.
Ongoing trials
ADAPT-SC+ trial
The ongoing Phase 3 ADAPT-SC+ trial (NCT04818671) is investigating the long-term safety and tolerability of Vyvgart Hytrulo for up to 3.5 years. Most patients who completed ADAPT-SC opted to enroll in the open-label extension study, which also included patients who had previously participated in other clinical trials of Vyvgart.
Interim, six-month data from ADAPT-SC+ showed that Vyvgart Hytrulo had a consistent effect in easing disease symptoms with each cycle of treatment. No new safety concerns were identified with longer treatment.
This trial is expected to conclude in December 2024.
Common side effects of Vyvgart Hytrulo
The most common side effects of efgartigimod alfa and Vyvgart Hytrulo reported in clinical trials of gMG patients were:
- respiratory tract infections
- headache
- urinary tract infection
- injection site reactions (redness, itching, bruising, and pain at the injection site).
Infections
Vyvgart Hytrulo may increase the risk of infections. The most commonly reported infections in clinical trials among patients treated with efgartigimod alfa were those involving the urinary and respiratory tracts. Most of these were considered to be mild to moderate in severity.
Patients on Vyvgart Hytrulo should be closely monitored for signs and symptoms of infections. It’s recommended that Vyvgart Hytrulo be withheld and appropriate treatment be given in patients experiencing a serious infection until that infection has resolved.
Allergic reactions
Allergic reactions, including breathing difficulties, swelling, and rash, have been observed in patients given Vyvgart Hytrulo and other efgartigimod alfa formulations. Urticaria, commonly known as hives, also has been reported in patients treated with Vyvgart Hytrulo. In clinical trials, these reactions were mild or moderate in severity, occurred within a few hours following therapy administration, and did not lead to treatment discontinuation.
Healthcare professionals should monitor patients for clinical signs and symptoms of an allergic reaction for at least 30 minutes following the administration of Vyvgart Hytrulo. If an allergic reaction occurs, appropriate measures should be instituted as needed, or the patient should seek medical attention.
Use in pregnancy and breastfeeding
There are no available data on the use of Vyvgart Hytrulo, or other products containing efgartigimod alfa, in pregnant people. Similarly, there is no information regarding the presence of efgartigimod alfa or hyaluronidase stemming from the administration of Vyvgart Hytrulo in breast milk, any potential effects on the breastfed infant, or on milk production.
In preclinical studies in animals, no evidence of abnormal fetal development or other adverse events were observed in the offspring when into-the-vein efgartigimod was given during pregnancy or lactation at much higher doses than those used in humans.
One study in which hyaluronidase was administered to mice during pregnancy and lactation at a dose up to 5,000 times higher than the recommended human dose showed no adverse effects on prenatal and/or postnatal development. However, increased embryo mortality and reduced fetal body weight were documented in another study in which hyaluronidase was given by subcutaneous injection to pregnant mice at the highest doses tested.
Patients who are pregnant or wish to become pregnant or breastfeed while using Vyvgart Hytrulo should discuss this with their healthcare providers.
Because Vyvgart Hytrulo is anticipated to reduce maternal IgG levels, it’s expected that passive immune protection typically provided by the mother to the newborn will be reduced. A risk-to-benefit analysis should be carried out before administering live or live-attenuated vaccines to infants who were exposed to Vyvgart Hytrulo in the womb.
Myasthenia Gravis News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
FAQs about Vyvgart Hytrulo
The U.S. Food and Drug Administration (FDA) approved Vyvgart Hytrulo in June 2023 to treat adults with generalized myasthenia gravis (gMG) who are positive for antibodies targeting the acetylcholine receptor. With that decision, Vyvgart Hytrulo became the first therapy administered via an under-the-skin injection to gain approval in the U.S. for gMG.
According to exploratory data from the ADAPT-SC trial, which supported the approval of Vyvgart Hytrulo for people with generalized myasthenia gravis (gMG), some patients may see results as early as one week after the last injection of a treatment cycle. However, each patient is unique and may respond differently to a given treatment; thus, a discussion with their healthcare team can help gMG patients better understand how Vyvgart Hytrulo may help in their particular case.
Hair loss and weight gain have not been reported in clinical trials as side effects of treatment with Vyvgart Hytrulo. Patients are advised to speak with their healthcare provider if they experience any unusual symptoms or side effects while on the medication.
There are no available data on the use of Vyvgart Hytrulo during pregnancy in humans. In animal studies, administration of efgartigimod alfa and hyaluronidase — both components of Vyvgart Hytrulo — were generally not associated with adverse developmental effects during pregnancy or after birth. Yet, it’s recommended patients who are pregnant or planning to become pregnant talk with their healthcare providers to know if the therapy is safe during that period.
Efgartigimod alfa, a key component of Vyvgart Hytrulo, has been reported to have no or a negligible impact on a person’s ability to drive and use machines. Nevertheless, it’s recommended patients be careful before attempting to drive or use any machines until they know how Vyvgart Hytrulo affects them. Patients starting treatment with Vyvgart Hytrulo should talk with their healthcare team regarding the treatment’s potential impact on daily activities like driving.
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