Argenx's Vyvgart Hytrulo snares 2nd US nod as FDA gives green light in autoimmune disease CIDP

For more than a decade, argenx has sought to apply its novel antibody fragment treatment approach to various autoimmune diseases. 

Its vision started to come into focus two and a half years ago with the FDA approval for Vyvgart in generalized myasthenia gravis (gMG). Now, the drug has won approval to treat its second indication in the U.S. and its third globally as the U.S. FDA cleared the med to treat the rare and debilitating peripheral nervous system disease chronic inflammatory demyelinating polyneuropathy (CIDP).

Late Friday, the FDA cleared the way for Argenx’s Vyvgart Hytrulo—the Halozyme-partnered subcutaneous version of its inaugural med Vyvgart (efgartigimod)—in CIDP as a weekly injection. 

The green light marks a breakthrough after three decades of “very little meaningful innovation” in the disease, Susan Begelman, M.D., argenx's VP of global medical affairs & evidence generation, said on a media call.

In CIDP, the drug boasts a "best-case scenario broad label," William Blair analysts Myles Minter, Ph.D., and Matt Phipps, Ph.D., wrote in a note to clients Monday. They noted that argenx plans to initially target 12,000 CIDP patients whose disease is not well-managed on current therapy. 

The company eventually aims to reach a total addressable population of 24,000 treated CIDP patients out of 41,000 diagnosed, the analysts added. 

CIDP is a rare autoimmune disease of the peripheral nervous system that causes fatigue, muscle weakness and loss of feeling in patients’ arms and legs. That weakness can worsen over time or come and go, with the potential for symptoms to significantly impair a person’s ability to function on a day-to-day basis. Without treatment, one-third of people living with CIDP will need a wheelchair, argenx has pointed out.

Historically, the treatment toolbox for CIDP consisted of steroids, intravenous (IV) or subcutaneous (subQ) immunoglobulins or plasma exchanges, Begelman explained. Takeda, for its part, recently won a U.S. CIDP approval for its subcutaneous immune globulin treatment HyQvia in January

Even still, given that many people with CIDP experience residual symptoms, argenx’s research has found that more than half of CIDP patients report being either somewhat or completely dissatisfied with their symptoms. In turn, these patients continue to seek novel treatment options.

As for Vyvgart Hytrulo, the drug works by inhibiting the neonatal FC receptors (FcRn) responsible for recycling IgG molecules, including autoantibodies, inside the body, Jeff Guptill, M.D., neuromuscular lead at argenx, said on the media call.

While the presumed autoimmune nature of CIDP is not fully understood, it’s hypothesized that the disease is caused by autoantibodies—immunoglobulin molecules that are directed or targeted against the myelin coating and certain other proteins that surround the axon or the nerve fiber, Guptill explained. The nerve fibers are responsible for sending electrical signals throughout the body.

Vyvgart Hytrulo’s latest approval is based on results from the late-stage ADHERE study—the largest ever performed in CIDP patients, according to Guptill—which found that 69% of patients responded to Vyvgart. At the same time, the drug helped slash patients’ risk of relapse by 61% compared with placebo.

The drug was also linked to a fast onset of action, with 40% of patients responding to the therapy by the study’s four-week mark.

Overall, argenx’s new approval marks a “big day and a historic moment for CIDP patients,” argenx’s chief operating officer, Karen Massey, said in an interview.

Argenx has been expanding its commercial teams “significantly” in preparation for its CIDP launch, increasing both the number of staffers as well as the types of roles needed to provide different types of support, she said.

As for the rationale behind that expansion decision, aside from scaling up in CIDP, the opportunity in myasthenia gravis appears “bigger than we initially thought,” Massey pointed out.

The COO also flagged a large prescriber overlap between the two diseases, noting that argenx is currently targeting about 10,000 prescribers across gMG and CIDP.

Among those prescribing for gMG, roughly 72% of neurologists also write scripts for CIDP, Massey said. Those prescribers already working with Vyvgart in gMG will provide an initial tailwind for the drug’s CIDP launch, she added.

Meanwhile, the company has already started discussions with payers, where appropriate, in a bid to establish broad access for CIDP, Massey noted.

Argenx has estimated the price of Vyvgart Hytrulo in CIDP is $450,000 per year, which is nearly twice the $250,000 average annual cost of infused and injected immunoglobulin maintenance therapies, Minter and Phipps' team at William Blair pointed out. 

"[W]e expect this to be a subject of discussion with payers given the cost differential, but patient out-of-pocket costs will be similar," the analysts said. 

In terms of awareness, argenx has been working on unbranded disease state education efforts with healthcare practitioners and targeting patients too with its Shining Through campaign.

Regarding the drug’s performance in its flagship myasthenia gravis indication, “the momentum we’ve had since launch just continues to grow,” Massey said.

After the drug's initial approval in December 2021, argenx generated $400 million in 2022. The figure swelled to nearly $1.2 billion last year. 

Argenx hopes to be in active development for 15 Vyvgart indications by 2025, the company said during this year’s J.P. Morgan Healthcare Conference in January. Analysts at ODDO BHF have predicted Vyvgart could rake in peak sales of $11 billion in 2035 across multiple indications. 

Editor's note: This story has been updated with additional details from a William Blair analyst note.