Vyvgart Hytrulo - 2 indications

• for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody positive; approved June of 2023 
• for the treatment of chronic inflammatory demyelinating polyneuropathy;  approved June of 2024

General Information

Vyvgart Hytrulo is a combination of efgartigimod alfa, a neonatal Fc receptor blocker, and hyaluronidase, an endoglycosidase.

Vyvgart Hytrulo is specifically indicated:

• for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody positive
• for the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP)  

Dosing/Administration

Vyvgart Hytrulo is supplied as a solution for subcutaneous injection. 

Because Vyvgart Hytrulo causes transient reduction in IgG levels, immunization with live attenuated or live vaccines is not recommended during treatment with Vyvgart Hytrulo. Evaluate the need to administer age-appropriate immunizations according to immunization guidelines before initiation of a new treatment cycle with Vyvgart Hytrulo.

Scroll down for the recommended dosing guidelines for each indication.

Mechanism of Action

Vyvgart Hytrulo is a coformulation of efgartigimod alfa and hyaluronidase.

Efgartigimod alfa is a human IgG1 antibody fragment that binds to the neonatal Fc receptor (FcRn), resulting in the reduction of circulating IgG.

Hyaluronidase increases permeability of the subcutaneous tissue by depolymerizing hyaluronan. This effect is transient and permeability of the subcutaneous tissue is restored within 24 to 48 hours.

Side Effects

Adverse effects associated with the use of Vyvgart Hytrulo may include, but are not limited to, the following:

• respiratory tract infections
• headache
• urinary tract infection

Indication 1 - AChR antibody positive generalized myasthenia gravis (gMG) 

The recommended dosage of Vyvgart Hytrulo is 1,008 mg / 11,200 units (1,008 mg efgartigimod alfa and 11,200 units hyaluronidase) administered subcutaneously over approximately 30 to 90 seconds in cycles of once weekly injections for 4 weeks.

Administer subsequent treatment cycles according to clinical evaluation. The safety of initiating subsequent cycles sooner than 50 days from the start of the previous treatment cycle has not been established.

 If a scheduled dose is missed, Vyvgart Hytrulo may be administered up to 3 days after the scheduled time point. Thereafter, resume the original dosing schedule until the treatment cycle is completed.

FDA approval of Vyvgart Hytrulo was based on positive results from the Phase 3 ADAPT-SC study, which established the efficacy of Vyvgart Hytrulo by demonstrating a reduction in anti-AChR antibody levels comparable to intravenous Vyvgart in adult gMG patients. ADAPT-SC was a bridging study to the Phase 3 ADAPT study, which formed the basis for approval of intravenous Vyvgart in December 2021.

In the ADAPT-SC study, the primary endpoint of noninferiority was met and Vyvgart Hytrulo demonstrated mean total IgG reduction of 66.4% from baseline at day 29, compared to 62.2% with Vyvgart. Additional key secondary endpoints were met, which were consistent with efficacy measures from the ADAPT study identifying the correlation between total IgG reduction and clinical benefit in gMG.

Indication 2 - chronic inflammatory demyelinating polyneuropathy

The FDA approval of Vyvgart Hytrulo for CIDP was based on the ADHERE study.

The study enrolled 322 adult patients with CIDP who were treatment naïve (not on active treatment within the past six months or newly diagnosed) or being treated with immunoglobulin therapy or corticosteroids. The trial consisted of an open-label Stage A followed by a randomized, placebo-controlled Stage B. Patients entered a run-in stage, where any ongoing CIDP treatment was stopped and in order to be eligible for Stage A had to demonstrate active disease, with clinically meaningful worsening on at least one CIDP clinical assessment tool, including INCAT, I-RODS, or mean grip strength. Treatment naïve patients were able to skip the run-in period with proof of recent worsening. To advance to Stage B, patients needed to demonstrate evidence of clinical improvement (ECI) with Vyvgart Hytrulo. ECI was achieved through improvement of the INCAT score, or improvement on I-RODS or mean grip strength if those scales had demonstrated worsening during the run-in period. In Stage B, patients were randomized to either Vyvgart Hytrulo or placebo for up to 48 weeks. The primary endpoint was measured once 88 total relapses or events were achieved in Stage B and was based on the hazard ratio for the time to first adjusted INCAT deterioration (i.e. relapse).

In the study, 69% (221/322) of patients treated with Vyvgart Hytrulo, regardless of prior treatment, demonstrated evidence of clinical improvement, including improvements in mobility, function and strength. ADHERE met its primary endpoint (p<0.0001) demonstrating a 61% reduction in the risk of relapse versus placebo.