US regulators have approved the first-in-class drug efgartigimod for the treatment of the rare muscle disease generalized myasthenia gravis, opening up its developer argenx to billion-dollar revenues.
Efgartigimod, to be marketed as Vyvgart, is an antibody fragment drug for use in adults with generalized myasthenia gravis. The FDA’s decision represents the first successful drug approval for argenx.
According to Evaluate Vantage Pharma, the drug is predicted to make €2.7B ($3B) in sales by 2026. argenx has also applied for approval in the EU, which is expected in summer 2022. The firm has also made a similar application in Japan.
“This is a tremendously exciting moment for the company,” said Jon Beauchamp, argenx’s Vice President and Head of EU Medical Affairs. He added that the hope was that efgartigimod would provide a “step change” in the care of patients.
“We hear about stories of mothers who can’t pick up their babies for example or their children because they are so debilitated by this muscle weakness.”
Generalized myasthenia gravis is a chronic autoimmune condition affecting approximately 15 in every 100,000 people. In this disease, antibodies mistakenly attack the site of communication between nerves and muscles, called the neuromuscular junction.
Patients become tired, with vision, limbs, and breathing also affected. They rarely reach remission with current typical treatments, which generally consist of steroids and broad immunosuppressants.
Efgartigimod brings a new, targeted approach that selectively removes the antibodies that are causing the damage. It does so by blocking a protein called neonatal Fc receptor (FcRn), which normally stops IgG antibodies from being cleared from the blood – the type that includes the autoantibodies attacking the patient’s healthy tissue. Blocking FcRn means more IgG autoantibodies are taken away, stopping damage at the neuromuscular junction.
The drug was first conceived in 2013, when argenx came up with the novel approach of utilizing a fragment of an antibody – the Fc fragment – which is very effective at blocking the FcRn receptor.
“It’s a new mechanism of action, of course… it’s an innovative new drug so we have to spend some time educating about that,” Beauchamp acknowledged. “But physicians really do understand it, once they understand the mechanism of action, they see that it is really a rational approach.”
Lenny Van Steenhuyse, Associate Director of Corporate Finance, Life Sciences, at KBC Securities, agreed that professionals would need guidance.
“Although efgartigimod is anticipated to become a multi-blockbuster, initial commercial rollout is anticipated to be slow,” he said. “This relates to FcRn as a novel mode of action and the need for quite some physician education on the drug.”
Van Steenhuyse noted that myasthenia gravis also had quite a variable presentation, leading to the need for individualized dosing regimens.
“As such, adoption is expected to be more modest given the less straightforward usage of the drug. Also, establishing reimbursement after approval is a process that requires some months, and adoption will mainly be driven by reimbursement,” said Van Steenhuyse.
Efgartigimod is delivered through cycles of intravenous infusion, with each infusion taking about an hour. But argenx is also working on a subcutaneous version for more convenient administration.
Competition for efgartigimod in generalized myasthenia gravis is fierce and currently falls into two main categories: other anti-neonatal FcRn blocker drugs in clinical trials and treatments that block C5, a protein that promotes inflammation and is involved in many autoimmune conditions including ANCA-associated vasculitis.
Other anti-neonatal FcRn blockers include UCB’s rozanolixizumab, which has the potential advantage of a subcutaneous infusion. Positive phase III study results have just been announced and the company plans to make regulatory filings in the US, EU, and Japan in the third quarter of 2022.
Among the C5 inhibitors, ravulizumab-cwvz returned positive phase III findings in summer. The drug’s developer, the AstraZeneca-owned Alexion, plans to make regulatory filings in the US, EU and Japan by early 2022.
Ravulizumab-cwvz is a successor to eculizumab, for which Alexion won FDA approval in 2017 – making it the first US approval for generalized myasthenia gravis in more than 60 years.
argenx is developing efgartigimod for six other autoimmune diseases where IgG antibodies are involved, including the blood disorder immune thrombocytopenia and the skin blistering disorder pemphigus vulgaris. The aim is to have 15 diseases under study by 2025.
argenx also has the investigational antibody cancer drug cusatuzumab, for which there was previously an alliance with Janssen. However, Janssen returned the rights to argenx earlier this year after the big pharma was disappointed by phase II results from the drug. argenx is working out what the next development steps will be.
Nonetheless, argenx has raised enormous funding in the past, and with an approval under its belt, the company may be able to bankroll more of its own research going forward.
Cover image via Anastasiia Slynko. Inline table via Jon Smith