After a string of clinical failures, the Dutch biotech argenx landed a much-needed win on Friday when the FDA approved its autoimmune disease drug, Vyvgart, for a second rare condition.
The disease, known as chronic inflammatory demyelinating polyradiculoneuropathy, or CIDP, arises when a person’s immune system attacks the protective insulation around their nerves. It’s more common in men and can cause fatigue, numbness, weakness and a “pins and needles” feeling in the limbs.
There are about 24,000 people with CIDP in the US under treatment, and standard therapies such as steroids and intravenous immunoglobulins don’t work for everyone. In a Phase 2 study, argenx showed its drug reduced the risk of relapse by 61% compared to placebo in a sizable subset of patients who showed improvements on the drug in a brief trial period.
The drug was approved as a once-weekly injection for adults with CIDP, regardless of whether they’ve tried older treatments first. “This is the best case scenario,” argenx CEO Tim Van Hauwermeiren said during a call with investors Friday evening.
Injectable and infusible forms of argenx’s drug are already approved for myasthenia gravis, another autoimmune condition, and last year brought in sales of $1.2 billion. It’s argenx’s sole product, and the company has wooed investors with plans to potentially treat more than a dozen autoimmune diseases with it, echoing the strategy that turned AbbVie’s Humira into an all-time blockbuster.
The scientific rationale for the strategy seems sound: Vyvgart helps flush out the self-sabotaging “autoantibodies” believed to be responsible for many autoimmune conditions. It works by blocking a common protein called FcRn, which cells use to recycle antibodies and keep them circulating in the blood.
With promising results in several early studies and strong sales in myasthenia gravis, argenx’s market cap breached $30 billion last summer. But the company’s value fell as low as $20 billion after the drug failed to beat placebo in Phase 3 trials for two autoimmune conditions: a blood platelets disease called primary immune thrombocytopenia, or ITP, and a skin-blistering disease called pemphigus. (Despite the failure, Vyvgart was approved for ITP in Japan.)
And in June, Vyvgart failed in a Phase 2 study of people who developed a cardiac condition called postural orthostatic tachycardia syndrome after a Covid-19 infection. But the company remains bullish about Vyvgart’s sweeping potential and plans to reveal topline data from its own study in another autoimmune condition, called Sjögren’s disease, in July.
Other companies, including Johnson & Johnson and Roivant, also have big ambitions with their own FcRn inhibitors, and J&J recently also unveiled positive data testing its drug in Sjögren’s disease.
A new option for an overlooked disease
The dose and frequency of the drug vary by patient. Last summer, argenx estimated that Vyvgart costs $225,000 annually for the average myasthenia gravis patient. During the investor call on Friday, the company said out-of-pocket costs will be similar for people with CIPD, but that the more frequent dosing means it could earn roughly $450,000 a year from those patients.
Chief operating officer Karen Massey said the company will initially focus on an estimated 12,000 patients who are not well-managed by their current therapy.
Treatments for CIDP have seen relatively little innovation in decades. Steroids are used to broadly tamp down the immune system. Immunoglobulin infusions or injections — often used to treat immune deficiencies — also seem to help some people, although it’s not entirely clear why. Some patients get their blood filtered in a process called plasmapheresis, and by helping clear out a person’s antibodies, Vyvgart may prove to be a more convenient alternative to that cumbersome procedure.
In its Phase 2 study, argenx first tested whether CIDP patients improved on the drug during a 12-week trial period. Improvement could be the difference between going from requiring a wheelchair to using a walker, or from needing both hands on a walker to using a simple cane.
According to the company’s press release last summer (the data haven’t been published in a medical journal yet), 67% of patients had meaningful improvements. Those patients moved on to the second stage of the study, where they were randomly assigned to continue receiving the drug or get a placebo injection. After 48 weeks, only 34% of patients on Vyvgart relapsed, compared to 60% on placebo.
The difference was statistically significant and helped bolster the notion that autoantibodies are an important part of the disease in some people. But the drug doesn’t work for everyone, and argenx doesn’t have a good way of predicting who is most likely to benefit.
“Unfortunately there hasn’t been anything that’s really stood out to us as being an ‘aha moment’ where we understood response versus lack of response,” Jeff Guptill, neuromuscular lead at argenx, told Endpoints News during a press briefing. The company is conducting biomarker studies to understand this further, he added.
Sanofi is testing a drug based on a different mechanism in CIDP patients. At a neurology conference in April, it presented positive but early data from a Phase 2 study of riliprubart, an antibody that inhibits an innate immune system protein called C1s that can trigger a cascade of inflammation and cell death.
Editor’s note: This story was updated with information from the argenx investor call, including drug pricing.