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Subcutaneous efgartigimod PH20 granted approval by the FDA for the treatment of CIDP

On 21st June 2024, the U.S Food and Drug Administration approved subcutaneous efgartigimod alfa and hyaluronidase-qvfc combination injection (efgartigimod PH20; VYVGART Hytrulo) for the treatment of adults diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP). This marks the first approval of a neonatal Fc receptor (FcRn) blocker to treat CIDP.1

CIDP is a rare, immune-mediated, neurological disorder characterized by fatigue, progressive muscle weakness, and impaired sensory function in the limbs. The autoimmune disorder is believed to result from dysfunctional immune responses to unknown antigens, although the specific triggering events and pathophysiological mechanisms involved remain unclear.2 The disease affects peripheral nerves by destroying the myelin sheaths surrounding nerve fibers and causing inflammation of nerve roots. Some patients with CIPD experience a relapse of symptoms after stabilizing, while others experience a progressive decline. Early diagnosis is crucial, as around 90% of people diagnosed with CIDP improve with treatment; without it, permanent nerve damage and disability may occur.3

Currently, the most common treatments for CIDP include corticosteroids such as prednisone, plasma exchange procedures, and intravenous immunoglobulin.3 Steroid-sparing immunosuppressive agents may also be utilized for maintenance therapy. While corticosteroids can often provide long-term remission from CIDP symptoms through their anti-inflammatory action, there is a significant risk of serious side effects when used for a prolonged period of time. These include osteoporosis, high blood pressure, and sleep and mood changes.3 These side effects, coupled with the disease burden of CIDP, can significantly impact a patient’s quality of life and adherence to treatment. Moreover, there are no clear indicators of which patient groups may benefit from specific therapies.

Recent evidence emerging from clinical trials highlights the role of IgG antibodies in facilitating the pathology seen in CIDP, making efgartigimod PH20 an exciting advancement in the search for a new treatment. Efgartigimod alfa, a human recombinant IgG antibody fragment, acts by binding and blocking FcRn. This prevents FcRn from recycling IgG, thereby reducing circulating IgG levels.4 In doing so, efgartigimod alfa inhibits IgG immune-complex mediated responses and so ameliorates the symptoms associated with autoimmune disease.5 The addition of recombinant human hyaluronidase PH20 facilitates subcutaneous injection delivery of the biologic. Its unique mechanism of action targeting IgG-driven pathogenesis, ease of administration, and favorable safety profile make it a promising alternative to current treatments. This landmark drug approval is the first of its kind in the field of CIDP and remains the first and only FcRn antagonist approved by the FDA that is administered by subcutaneous injection.1

“Today’s approval of VYVGART Hytrulo gives doctors and patients a new, safe and effective treatment option that may lessen the burden of treatment that some patients experience.” -Jeffrey Allen, MD, Professor, University of Minnesota and Principal Investigator in the ADHERE trial.4

“Patients have been waiting, and today argenx is delivering the first innovative treatment for CIDP in more than 30 years” -Luc Truyen, MD, PhD, chief medical officer of argenx.4

The FDA’s milestone approval of efgartigimod PH20 comes after the publication of data from the Phase II ADHERE study (NCT04281472), the largest CIDP trial to date.6 This multicenter, randomized, double-blind, placebo-controlled trial was conducted on 322 adults with active CIDP and aimed to evaluate the safety and efficacy of efgartigimod PH20 compared to placebo. The trial consisted of a ≤12-week run-in period in which any current treatments were stopped, before an open-label Stage A of the same length in which subjects were administered 1000mg efgartigimod PH20 SC weekly. This was followed by the placebo-controlled Stage B in which treatment responders were randomized to receive up to 48-weeks of weekly treatment versus placebo.

The study met its Stage B primary endpoint – efficacy based on time to first deterioration of the INCAT disability score – with efgartigimod PH20 significantly reducing clinical deterioration compared to placebo (p=0.000039).6 The study saw a 61% reduction in the risk of relapse compared to placebo and observed clinical benefits across all patient subgroups, regardless of the treatment they were previously receiving. Notably, efgartigimod PH20 treatment was associated with clinically meaningful improvements in grip strength and activity/social participation in Stage A, which were maintained by those treated in Stage B, but lost by those receiving placebo.4 The drug’s safety profile was also consistent with the profile of efgartigimod and prior trials conducted. Common side effects were mild to moderate infections and hypersensitivity reactions.4

“With these positive ADHERE data, we have generated strong clinical evidence that CIDP has a significant IgG-driven pathogenesis component and that VYVGART Hytrulo can meaningfully improve and stabilize disease symptoms with a favorable safety profile and a simple route of administration” -Luc Truyen, MD, PhD, chief medical officer of argenx.4

Efgartigimod alfa is not only poised to improve CIDP treatment outcomes. In 2023, efgartigimod PH20 was approved for the treatment of anti-acetylcholine receptor antibody-positive myasthenia gravis in adults, following approval of an intravenous formulation in 2021. Efgartigimod is also being investigated for the treatment of other autoimmune diseases, such as immune thrombocytopenia, autoimmune myositis, and AChR-negative myasthenia gravis.

Despite available treatments, many patients with CIDP still suffer debilitating symptoms, with over half of patients experiencing severe disability as a result of CIDP at some point in their disease.3 Additionally, 10-15% of patients show resistance to all current treatments.3 The FDA’s endorsement of efgartigimod PH20 for CIDP treatment represents a significant advancement in its management, providing new hope of both addressing the underlying immune pathophysiology of CIDP and reducing side effects compared to alternative immunosuppressive therapies.

Written by Katie Robinson

Reviewed by Juliet Lawrence

References:

  1. Argenx. argenx Announces FDA Approval of VYVGART Hytrulo for Chronic Inflammatory Demyelinating Polyneuropathy [Press Release]. 21st June 2024. Accessed 21st June 2024.
  2. Dimachkie M, Barohn R. Chronic Inflammatory Demyelinating Polyneuropathy. Curr Treat Options Neurol. Jun 2013; 15(3):350-366.
  3. Gogia B, Rocha Cabrero F, Khan Suheb MZ, et al. Chronic inflammatory demyelinating polyradiculoneuropathy. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2023. Updated 4th March 2024. Accessed 21st June 2024.
  4. Argenx. argenx Reports Positive Topline Data from ADHERE Study of VYVGART Hytrulo in Patients with Chronic Inflammatory Demyelinating Polyneuropathy [Press Release]. 17th July 2023. Accessed 21st June 2024.
  5. Blumberg LJ, Humphries JE, Jones SD, et al. Blocking FcRn in humans reduces circulating IgG levels and inhibits IgG immune complex-mediated immune responses. Sci Adv. Dec 2019;5(12):eaax9586.
  6. Allen J, Basta I, Eggers C, et al. Efficacy, Safety, and Tolerability of Efgartigimod in Patients with Chronic Inflammatory Demyelinating Polyneuropathy: Results from the ADHERE Trial (PL5.002). Neurology. Apr 2024; 102 (17_supplement_1)