Submission bundle primarily based on optimistic information from the Phase 3 ADAPT-SC trial demonstrating noninferiority of subcutaneous (SC) efgartigimod in contrast to intravenously administered VYVGART® (efgartigimod alfa-fcab) primarily based on complete immunoglobulin G (IgG) discount at day 29
Amsterdam, the Netherlands – September 21, 2022 – argenx SE (Euronext & Nasdaq: ARGX), a worldwide immunology firm dedicated to enhancing the lives of individuals affected by extreme autoimmune illnesses, as we speak introduced the submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for SC efgartigimod (1000mg efgartigimod-PH20) for the therapy of generalized myasthenia gravis (gMG) in grownup sufferers.
SC efgartigimod is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE® drug supply expertise. ENHANZE facilitates the subcutaneous injection supply of biologics which might be usually administered by way of intravenous (IV) infusion.
“Our vision for the gMG program is to deliver the broadest treatment offering for people living with this debilitating, and often overlooked disease. Every individual experiences gMG differently, which is why we’re excited about the possibility of introducing multiple ways to meet the needs of patients, including with route of administration and dosing schedule,” stated Tim Van Hauwermeiren, Chief Executive Officer of argenx. “The submission of this BLA is the latest milestone in honoring our commitment to the gMG patient community. We look forward to working closely with the agency through the BLA review process and to potentially bringing forth another first-in-class option for gMG patients.”
The BLA submission bundle consists of information from the Phase 3 ADAPT-SC research evaluating the noninferiority of the pharmacodynamic (PD) impact of SC efgartigimod as in contrast with intravenously administered VYVGART in grownup sufferers with gMG. The majority of enrolled sufferers have been optimistic for acetylcholine receptor (AChR) antibodies, however the trial additionally included sufferers the place AChR antibodies weren’t detected.
ADAPT-SC met its major endpoint (p< 0.0001) of complete IgG discount from baseline at day 29 demonstrating noninferiority of SC efgartigimod to VYVGART. Patients handled with SC efgartigimod achieved imply complete IgG discount of 66.4% from baseline at day 29, in contrast to 62.2% discount with VYVGART. Results have been constant throughout the general inhabitants, together with these with AChR antibodies and sufferers the place AChR antibodies weren’t detected. Further, 69.1% of sufferers handled with SC efgartigimod have been responders on the Myasthenia Gravis Activities of Daily Living (MG-ADL) rating. Responders are outlined as having not less than a two-point enchancment on the MG-ADL rating for not less than 4 consecutive weeks. 65.5% of sufferers handled with SC efgartigimod have been responders on the Quantitative Myasthenia Gravis (QMG) rating. Responders are outlined as having not less than a three-point enchancment on the QMG rating for not less than 4 consecutive weeks. Minimal symptom expression (MSE), a measure of symptom-free standing, was achieved in 37% of SC efgartigimod-treated sufferers after one therapy cycle. Onset of impact was additionally in step with the Phase 3 ADAPT research.
The security profile for SC efgartigimod was in step with the ADAPT research. It was usually well-tolerated; probably the most frequent opposed occasion being injection web site reactions (ISRs), generally noticed with biologics administered subcutaneously. All ISRs have been gentle to average and resolved over time. After finishing ADAPT-SC, 95% of contributors entered ADAPT-SC+, a three-year open-label extension research evaluating the long-term security and tolerability of SC efgartigimod.
Phase 3 ADAPT-SC Trial Design
The Phase 3 ADAPT-SC trial was a multicenter, randomized, open-label, parallel-group research evaluating the noninferiority of the pharmacodynamic (PD) impact of SC efgartigimod (1000mg efgartigimod-PH20) as in contrast with VYVGART (10mg/kg) in sufferers with gMG. The pharmacodynamic impact as measured by p.c change from baseline in complete IgG ranges at day 29, one week after the final dose of IV or SC efgartigimod, served as the first endpoint within the ADAPT-SC trial. The correlation between complete IgG discount and medical profit in gMG was demonstrated in a Phase 2 trial and the Phase 3 ADAPT trial, which served as the idea for approval of VYVGART within the U.S., Japan and Europe. Safety, medical efficacy, immunogenicity and pharmacokinetics (PK) have been additionally assessed.
A complete of 110 grownup sufferers with gMG in North America, Europe and Japan enrolled within the ADAPT-SC trial and have been handled. Inclusion standards of the trial have been the identical because the Phase 3 ADAPT trial of VYVGART; enrolled sufferers had a confirmed gMG prognosis and an MG-ADL complete rating of not less than 5 with larger than 50% of the full rating attributed to non-ocular signs, at screening and baseline. Patients have been on a secure dose of not less than one gMG therapy prior to randomization, together with acetylcholinesterase inhibitors, corticosteroids or nonsteroidal immunosuppressive medicine, and have been required to stay on that secure dose all through the first trial. Patients have been eligible to enroll in ADAPT-SC no matter antibody standing, together with sufferers with AChR antibodies (AChR-Ab+) and sufferers the place AChR antibodies weren’t detected.
Patients have been randomized in a 1:1 ratio to obtain SC efgartigimod or IV efgartigimod for one therapy cycle consisting of 4 doses at weekly intervals. The complete research period was roughly 12 weeks, together with seven weeks of follow-up after the therapy cycle.
See the complete Prescribing Information for VYVGART within the U.S., which incorporates the under Important Safety Information. For extra info associated to VYVGART in Japan, go to argenx.jp.
IMPORTANT SAFETY INFORMATION FOR VYVGART® (efgartigimod alfa-fcab) intravenous (IV) formulation (U.S. PRESCRIBING INFORMATION)
What is VYVGART® (efgartigimod alfa-fcab)?
VYVGART is a prescription drugs used to deal with a situation known as generalized myasthenia gravis, which causes muscle mass to tire and weaken simply all through the physique, in adults who’re optimistic for antibodies directed towards a protein known as acetylcholine receptor (anti-AChR antibody optimistic).
What is crucial info I ought to find out about VYVGART?
VYVGART might trigger severe unintended effects, together with:
- Infection. VYVGART might improve the danger of an infection. In a medical research, the commonest infections have been urinary tract and respiratory tract infections. More sufferers on VYVGART vs placebo had under regular ranges for white blood cell counts, lymphocyte counts, and neutrophil counts. The majority of infections and blood unintended effects have been gentle to average in severity. Your well being care supplier ought to verify you for infections earlier than beginning therapy, throughout therapy, and after therapy with VYVGART. Tell your well being care supplier in case you have any historical past of infections. Tell your well being care supplier instantly in case you have indicators or signs of an an infection throughout therapy with VYVGART similar to fever, chills, frequent and/or painful urination, cough, ache and blockage of nasal passages/sinus, wheezing, shortness of breath, fatigue, sore throat, extra phlegm, nasal discharge, again ache, and/or chest ache.
- Undesirable immune reactions (hypersensitivity reactions). VYVGART may cause the immune system to have undesirable reactions similar to rashes, swelling beneath the pores and skin, and shortness of breath. In medical research, the reactions have been gentle or average and occurred inside 1 hour to 3 weeks of administration, and the reactions didn’t lead to VYVGART discontinuation. Your well being care supplier ought to monitor you throughout and after therapy and discontinue VYVGART if wanted. Tell your well being care supplier instantly about any undesirable reactions.
Before taking VYVGART, inform your well being care supplier about your whole medical situations, together with when you:
- Have a historical past of an infection otherwise you suppose you may have an an infection
- Have obtained or are scheduled to obtain a vaccine (immunization). Discuss together with your well being care supplier whether or not you want to obtain age-appropriate immunizations earlier than initiation of a brand new therapy cycle with VYVGART. The use of vaccines throughout VYVGART therapy has not been studied, and the protection with stay or live-attenuated vaccines is unknown. Administration of stay or live-attenuated vaccines is just not really useful throughout therapy with VYVGART.
- Are pregnant or plan to turn out to be pregnant and are breastfeeding or plan to breastfeed.
Tell your well being care supplier about all of the medicines you are taking, together with prescription and over-the-counter medicines, nutritional vitamins, and natural dietary supplements.
What are the frequent unintended effects of VYVGART?
The most typical unintended effects of VYVGART are respiratory tract an infection, headache, and urinary tract an infection.
These should not all of the potential unintended effects of VYVGART. Call your physician for medical recommendation about unintended effects. You might report unintended effects to the US Food and Drug Administration at 1-800-FDA-1088.
Please see the complete Prescribing Information for VYVGART and discuss to your physician.
Efgartigimod is an antibody fragment designed to scale back pathogenic immunoglobulin G (IgG) antibodies by binding to the neonatal Fc receptor and blocking the IgG recycling course of. Efgartigimod is being investigated in a number of autoimmune illnesses identified to be mediated by disease-causing IgG antibodies, together with neuromuscular issues, blood issues, and pores and skin blistering illnesses, in each an intravenous and subcutaneous (SC) formulation. SC efgartigimod is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE® drug supply expertise.
VYVGART® (efgartigimod alfa-fcab) is a human IgG1 antibody fragment that binds to the neonatal Fc receptor (FcRn), ensuing within the discount of circulating immunoglobulin G (IgG) autoantibodies. It is the primary and solely permitted FcRn blocker. VYVGART is permitted within the United States and Europe for the therapy of adults with generalized myasthenia gravis (gMG) who’re anti-acetylcholine receptor (AChR) antibody optimistic, and in Japan for the therapy of adults with gMG who don’t have adequate response to steroids or non-steroidal immunosuppressive therapies (ISTs).
About Generalized Myasthenia Gravis
Generalized myasthenia gravis (gMG) is a uncommon and continual autoimmune illness the place IgG autoantibodies disrupt communication between nerves and muscle mass, inflicting debilitating and doubtlessly life-threatening muscle weak point. Approximately 85% of individuals with MG progress to gMG inside 24 months1, the place muscle mass all through the physique could also be affected. Patients with confirmed AChR antibodies account for roughly 85% of the full gMG inhabitants1.
argenx is a worldwide immunology firm dedicated to enhancing the lives of individuals affected by extreme autoimmune illnesses. Partnering with main tutorial researchers by its Immunology Innovation Program (IIP), argenx goals to translate immunology breakthroughs right into a world-class portfolio of novel antibody-based medicines. argenx developed and is commercializing the first-and-only permitted neonatal Fc receptor (FcRn) blocker within the U.S., Japan and the EU. The Company is evaluating efgartigimod in a number of severe autoimmune illnesses and advancing a number of earlier stage experimental medicines inside its therapeutic franchises. For extra info, go to www.argenx.com and comply with us on LinkedIn, Twitter, and Instagram.
Forward Looking Statements
The contents of this announcement embody statements which might be, or could also be deemed to be, “forward-looking statements.” These forward-looking statements will be recognized by way of forward-looking terminology, together with the phrases “believes,” “hope,” “estimates,” “anticipates,” “expects,” “intends,” “may,” “will,” or “should” and embody statements argenx makes regarding the submission of the Biologics License Application to the U.S. Food and Drug Administration for Subcutaneous (SC) Efgartigimod for Treatment of Generalized Myasthenia Gravis and the long-term security and tolerability of SC Efgartigimod. By their nature, forward-looking statements contain dangers and uncertainties and readers are cautioned that any such forward-looking statements should not ensures of future efficiency. argenx’s precise outcomes might differ materially from these predicted by the forward-looking statements because of varied necessary components. An additional checklist and outline of those dangers, uncertainties and different dangers will be present in argenx’s U.S. Securities and Exchange Commission (SEC) filings and stories, together with in argenx’s most up-to-date annual report on Form 20-F filed with the SEC in addition to subsequent filings and stories filed by argenx with the SEC. Given these uncertainties, the reader is suggested not to place any undue reliance on such forward-looking statements. These forward-looking statements converse solely as of the date of publication of this doc. argenx undertakes no obligation publicly replace or revise the data on this press launch, together with any forward-looking statements, besides as could also be required by legislation.
1 Behin et al. New Pathways and Therapeutics Targets in Autoimmune Myasthenia Gravis. J Neuromusc Dis 5. 2018. 265-277