FDA approves under-the-skin Vyvgart Hytrulo to treat gMG
New efgartigimod formulation takes less than 2 minutes to administer
Note: This story was updated June 28, 2023, to correct the time frame of the ADAPT-SC+ clinical trial, in which patients will be treated for up to 3.5 years.
The newly approved therapy is indicated for gMG patients who are positive for antibodies against the acetylcholine receptor (AChR) — the most common type of MG-driving self-reactive antibodies.
Vyvgart Hytrulo is an under-the-skin, or subcutaneous, product combination of efgartigimod alfa, the active agent in Argenx’s into-the-vein gMG therapy Vyvgart, and a recombinant, or man-made, human hyaluronidase PH20 enzyme. That enzyme plays a key role in the treatment’s subcutaneous mode of delivery.
With this approval, Vyvgart Hytrulo has now become the first FDA-approved gMG therapy to be delivered via an under-the-skin injection, which takes less than two minutes — up to 90 seconds — to be administered. In comparison, the into-the-vein or intravenous therapy takes about one hour.
“[The FDA’s] approval of Vyvgart Hytrulo is another significant milestone on our path to redefine what well-controlled means for gMG patients,” Luc Truyen, MD, PhD, Argenx’s chief medical officer, said in a company press release, adding, “With our broad gMG offering of both a first-in-class infusion and [subcutaneous] injection, we continue to offer an individualized treatment approach and [the] possibility of staying symptom free, while providing patients options of how and where they want to seek treatment.”
Approval hailed by patients, advocates
As stated in its label, Vyvgart Hytrulo should be administered by a healthcare professional. The medication should be given via a single subcutaneous injection containing a fixed dose of 1,008 mg of efgartigimod alfa over a period of 30 to 90 seconds, in cycles of once weekly injections lasting four weeks.
In addition to its much shorter administration time, Vyvgart Hytrulo also gives patients the opportunity to be given the medication at home — an option generally not possible with the intravenous formulation.
Such advances are particularly noteworthy, according to Sharon Hesterlee, PhD, chief research officer of the Muscular Dystrophy Association (MDA), given that few treatment options were available a decade ago.
“The approval of an additional formulation of Vyvgart is another important step toward treating gMG, a disease that, up until a few years ago, had no approved therapies,” Hesterlee said in an MDA press release.
“Now those living with gMG will have the choice to receive a subcutaneous injection of an effective disease modifying therapeutic,” Hesterlee said.
The decision was well received by the patient community, as well as by several patient organizations and associations.
“The availability of another gMG treatment option from Argenx, now in a subcutaneous delivery, is a meaningful advancement for the patient community,” said Allison Foss, executive director of the Myasthenia Gravis Association.
“Patients now have the opportunity to receive treatment in an infusion center, at home or at a physician’s office — providing more flexibility and freedom of choice that can make daily living easier for gMG patients and their caregivers,” Foss said.
Stephanie Madole is a mother of two daughters with gMG. While both are on other therapies, she called the FDA approval “an exciting step forward.”
“I feel the new formulation of Vyvgart has the potential to be more convenient, which will definitely make a difference for many families,” Madole said, adding, “Continued research and more therapeutic options are imperative.”
“The new formulation replaces a one-hour infusion with a shot given at home; which matters for families like ours who drive 8 hours round trip for infusions and our girls miss school and days where they’re able to spend time just being kids,” Madole said.
Vyvgart Hytrulo likely available in July
According to Argenx, Vyvgart Hytrulo should become available to patients in the U.S. in July. As part of its commitment to supporting patients’ access to its medicines, Argenx has decided to price Vyvgart Hytrulo at parity with its previously approved gMG therapy, Vyvgart.
Additionally, the company is placing Vyvgart’s patient personalized support program, My Vyvgart Path, at the disposal of patients starting treatment with Vyvgart Hytrulo. The program includes useful resources and information on disease education, as well as on financial assistance programs.
The FDA’s decision comes about nine months after Argenx initially filed the regulatory application and about seven months after the agency granted it priority review. Early this year, the FDA delayed by three months its review deadline, initially set for mid-March, so it could thoroughly analyze additional information submitted by Argenx.
Subcutaneous efgartigimod also is under regulatory review both in the European Union and Japan. A decision in the EU is expected by year’s end, with action in the Asian nation anticipated early next year.
In MG, the body’s immune system produces self-reactive antibodies that wrongly attack healthy proteins at neuromuscular junctions where nerve and muscle cells communicate.
Efgartigimod is an antibody fragment that binds to and blocks the activity of the neonatal Fc receptor, a protein that normally helps prevent antibodies circulating in the bloodstream from being destroyed. As such, it is expected to increase the rate at which the self-reactive antibodies that drive MG are broken down, lowering their levels in the blood and ultimately easing disease symptoms.
Vyvgart is an approved efgartigimod formulation that is administered directly into the bloodstream through hour-long infusions. One cycle of treatment consists of weekly infusions given over the course of four weeks, with additional treatment cycles given based on a patient’s clinical response.
The therapy is approved in the U.S. and other regions for adults with gMG who are positive for anti-AChR antibodies. Such patients make up about 85% of the total gMG population.
Vyvgart Hytrulo was designed to provide an efgartigimod formulation that was easier to administer than Vyvgart. It was developed using a technology from Halozyme Therapeutics, called ENHANZE. That technology facilitates the delivery of biologic therapies that are typically administered by infusion directly into the bloodstream. It relies on the use of a proprietary enzyme that breaks down a major component of skin tissue, facilitating the dispersion and absorption of medicines given via subcutaneous injection.
“We are pleased that Argenx has received FDA approval for the subcutaneous form of efgartigimod, which reinforces their commitment to the patient community with a broadening of treatment options that brings flexibility for patients,” Helen Torley, Halozyme’s president and CEO, said in another press release.
New efgartigimod formulation comparable to Vyvgart in trials
The therapy’s approval was supported mainly by data from the international Phase 3 ADAPT-SC clinical trial (NCT04735432). That trial tested Vyvgart Hytrulo against Vyvgart in 110 adults with gMG.
Participants, most of whom were positive for anti-AChR antibodies, were assigned randomly to receive weekly treatment with either Vyvgart Hytrulo (1,000 mg) or Vyvgart (10 mg/kg) for four weeks, or about one treatment cycle.
Results showed that Vyvgart Hytrulo was, at least, not inferior to Vyvgart in its ability to lower the levels of immunoglobulin G (IgG) — a class of antibodies that includes those implicated in MG — after 29 days of treatment (a mean drop of 66.4% vs. 62.2%). Comparable results between the two therapies were seen regardless of patients’ anti-AChR antibody status.
More than two-thirds (69.1%) of Vyvgart Hytrulo-treated patients experienced a clinically significant reduction in the disease’s impact on daily life, as reflected by a drop of two or more points on the MG Activities of Daily Living score for at least four consecutive weeks.
About as many patients on Vyvgart Hytrulo (65.5%) showed a similarly sustained reduction in disease severity, as reflected by a drop of at least three points on the Quantitative MG score.
More than one-third of patients (37%) were symptom-free after one treatment cycle of Vyvgart Hytrulo.
The therapy was tolerated well generally, with a safety profile comparable to that of Vyvgart. The most frequently reported side effects with the new formulation were mild-to-moderate injection site reactions, all of which resolved with time.
Now with the approval of Vyvgart Hytrulo, we have a broad gMG treatment offering with both [intravenous] and [subcutaneous] administration options and can select based on patient needs and preference without sacrificing clinical benefit or safety.
“The clinical trials of Vyvgart continue to show significant benefit to patients with a favorable safety profile and clear improvements in gMG disease scores. Now with the approval of Vyvgart Hytrulo, we have a broad gMG treatment offering with both [intravenous] and [subcutaneous] administration options and can select based on patient needs and preference without sacrificing clinical benefit or safety,” said James F. Howard Jr., MD, professor of neurology at the University of North Carolina at Chapel Hill School of Medicine and principal investigator in ADAPT-SC.
Most patients completing ADAPT-SC chose to enter an open-label extension study, called ADAPT-SC+ (NCT04818671), in which all will receive Vyvgart Hytrulo for up to 3.5 years. Repeated treatment cycles will be given as needed, separated by about one month or more.
Interim, six-month data showed that each Vyvgart Hytrulo cycle was associated with a reduction in disease severity and that no new safety concerns were identified with longer treatment.