Vyvgart Hytrulo for myasthenia gravis

Last updated Nov. 1, 2024, by Joana Carvalho, PhD
Fact-checked by Inês Martins, PhD

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 an injection under the skin, or subcutaneously, and is designed to ease symptoms in people with gMG. This administration method is expected to be easier and more convenient than with Vyvgart, the company’s older formulation of efgartigimod alpha that’s approved for the same indication but given via intravenous infusions, or into the bloodstream.

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.

Vyvgart Hytrulo is also approved for treating chronic inflammatory demyelinating polyneuropathy, a rare autoimmune disorder that affects nerves.

Therapy snapshot

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 the neonatal Fc receptor (FcRn) protein helps to stabilize IgG antibodies circulating in the bloodstream and prevent their destruction.

Like 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 infusion into a vein. 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 with myasthenia gravis 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.

The therapy was approved later that year for the same indication in Europe, where it is marketed as Vyvgart SC. Vyvgart Hytrulo is also approved in Japan under the brand name Vyvdura for adults with gMG who do not sufficiently respond to first-line treatment with steroids or nonsteroidal immunosuppressive therapies.

Who should not take Vyvgart Hytrulo?

Vyvgart Hytrulo is contraindicated, or not recommended, for patients with serious allergies to efgartigimod alfa, hyaluronidase, or any of the other components in the therapy.

How is Vyvgart Hytrulo administered in myasthenia gravis?

Vyvgart Hytrulo is administered via subcutaneous injections that should be given only by a trained healthcare professional. Administration takes approximately 30 to 90 seconds to complete.

Patients initially receive a first treatment cycle consisting of weekly injections over four weeks. Additional treatment cycles of four once-weekly injections are then given based on the 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.

During each infusion and for one hour thereafter, patients should be closely monitored by a healthcare professional for any signs of allergic reactions and appropriate measures should be instituted if such a reaction occurs.

The therapy’s recommended dose is 1,008 mg of efgartigimod alfa and 11,200 units of hyaluronidase. It’s supplied in single-dose vials containing 5.6 mL of a yellowish, clear to opalescent solution.

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 have passed, the original dosing schedule should be resumed until the treatment cycle is completed.

Because Vyvgart Hytrulo causes a temporary reduction in IgG levels, vaccination with live vaccines is not recommended during treatment. Before starting a new treatment cycle, the need to administer age-appropriate vaccines should be evaluated in all patients.

Vyvgart Hytrulo in clinical trials

The approvals of Vyvgart Hytrulo were 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 approved intravenous formulation Vyvgart in 110 adults with gMG enrolled at sites in North America, Europe, and Japan. The participants were randomly assigned to either four weekly doses of Vyvgart Hytrulo (1,000 mg) or Vyvgart and were followed for up to 10 weeks total.

The results showed Vyvgart Hytrulo was at least as effective as Vyvgart, or not inferior to it, in its ability to lower total IgG 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 anti-AChR antibody levels.

The subcutaneous formulation also led to improvements in two measures of disease severity, the MG Activities of Daily Living (MG-ADL) and Quantitative MG (QMG), that were consistent with those seen with Vyvgart.

Specifically, 69.1% of patients in each group attained clinically meaningful improvements in the MG-ADL, a patient-reported measure of disease severity, and meaningful improvements in QMG, a measure of MG severity as reported by clinicians, were observed in 65.5% of those given Vyvgart Hytrulo and in 51.9% of participants treated with Vyvgart. The safety profile of the two treatments also was similar.

Ongoing trials

After completing ADAPT-SC, most patients opted to enroll in an open-label extension study called ADAPT-SC+ (NCT04818671), which is investigating the long-term safety and tolerability of Vyvgart Hytrulo for up to three and a half years. The trial, which is still ongoing, also included patients who’d participated in other Vyvgart clinical trials.

Interim data from ADAPT-SC+ showed Vyvgart Hytrulo had a consistent effect in easing disease symptoms with each cycle of treatment. Specifically, a reduction of about 4 points in MG-ADL scores was seen in patients treated with Vyvgart Hytrulo during the first three treatment cycles. Moreover, around a third of patients achieved a state of minimal symptom expression (MG-ADL score of 0 or 1) at any point in the first three treatment cycles. No new safety concerns were identified with longer treatment.

Another ongoing Phase 2/3 clinical trial called ADAPT JR SC (NCT06392386) is assessing the safety and pharmacological properties of Vyvgart Hytrulo in children ages 2-17 with gMG. An estimated 12 participants are expected to enroll at sites in the U.S. and Europe.

Primary trial goals include evaluating blood levels of the therapy and IgG levels after treatment. Secondary goals include safety, changes in quality of life and measures of disease severity, as well as vaccine response after treatment. A long-term extension of that trial called ADAPT JR+ (NCT05374590) will then evaluate the treatment’s safety for up to four years. This extension, which is expected to finish in 2028, will also include participants given intravenous Vyvgart in a similar pediatric trial.

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 having 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 or Vyvgart Hytrulo. 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 to three weeks after being administered, and didn’t lead to treatment being discontinued.

In postmarketing studies of intravenous Vyvgart, anaphylaxis, which is a severe or potentially life-threatening allergic reaction, and low blood pressure resulting in fainting have occurred during or within one hour of administration. In some cases, these reactions led to permanent treatment discontinuation.

Healthcare professionals should monitor patients for clinical signs and symptoms of an allergic reaction for at least 30 minutes after Vyvgart Hytrulo is administered. If an allergic reaction occurs, appropriate measures should be instituted as needed, or the patient should seek medical attention.

Infusion-related reactions

Infusion-related reactions have been reported in patients treated with intravenous Vyvgart in postmarketing studies. Symptoms of such reactions included high blood pressure, chills, shivering, and pain in the chest, abdomen, and back. These reactions occurred during or within one hour after administration and led to infusion discontinuation.

The benefits and risks of readministering Vyvgart Hytrulo should be considered in patients who have experienced a severe infusion-related reaction. In those having a mild to moderate reaction, patients may be rechallenged with close clinical observation, slower infusion rates, and pre-medications.

Use in pregnancy and breastfeeding

There are no available data on pregnant people using efgartigimod alfa-based products. Similarly, there is no information on whether efgartigimod alfa or hyaluronidase can be found in breast milk after treatment with Vyvgart Hytrulo, or on their potential effects on the breastfed infant, or milk production.

In animal studies, no evidence of abnormal fetal development or other adverse events were observed when intravenous efgartigimod was given during pregnancy or lactation at much higher doses than those used in humans. A study in which hyaluronidase was given by subcutaneous injection to pregnant mice did report increased embryo mortality.

Patients who are pregnant or nursing, and those who wish to become pregnant or breastfeed, should discuss with their healthcare providers whether it’s safe to use Vyvgart Hytrulo.

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. Patients and healthcare providers should consider the potential risks and benefits before administering live vaccines to infants exposed to Vyvgart Hytrulo in the womb.

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