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New Medicines

VyvgartMyasthenia gravis with generalised muscle weakness (Myasthenia Gravis Foundation of America (MGFA) class II, III, IVa and IVb)

Information

Vyvgart
New molecular entity
argenx
argenx

Development and Regulatory status

Phase III Clinical Trials
Recommended for approval (Positive opinion)
Launched
Yes
Yes
Jun 22Recommended for EU approval by CHMP “as an add on to standard therapy for the treatment of adult patients with generalised Myasthenia Gravis (gMG) who are anti acetylcholine receptor (AChR) antibody positive”. Vyvgart will be available as 20mg/ml concentrate for solution for infusion [18].
May 22MHRA grants Early Access to Medicines Scheme (EAMS) status to efgartigimod for treatment of adult patients with AChR-antibody seropositive generalised myasthenia gravis (gMG), including patients with refractory gMG who have failed, not tolerated or are ineligible for licensed treatment [17].
Jan 22Launched in the US with a wholesale acquisition cost of $5,950 per vial. One year of treatment would cost a typical myasthenia gravis patient about $225,000 [16].
Dec 21Approved by the FDA for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody positive [15]
Aug 21EMA validate MAA for efgartigimod for treatment of generalized myasthenia gravis (gMG) [14].
Feb 21Efgartigimod is considered by analysts to be the third most anticipated drug launch of 2021 [11].
Jan 21 Argenx have submitted a Biologics License Application to the FDA for efgartigimod; they plan to file with the EMA in H2 2021 [9].
Nov 20Efgartigimod is on track to be filed in generalised myasthenia gravis over the coming weeks [8].
Mar 20Company announced plans to submit a BLA to US FDA before the end of 2020.[7]
Feb 20argenx has received fast track designation for efgartigimod in MG from the FDA and expects to file a Biologics License Application (BLA) in Q4 2020 with launch planned for 2021. The company also plans to engage with the FDA in 2020 on a potential bridging strategy for 1000mg subcutaneous (SC) ENHANZE®-efgartigimod. No plans for EU development are described in the argenx latest business update [6].
Mar 18EU orphan status for treatment of myasthenia gravis granted; the FDA had previously also granted orphan status for the US [1].

Category

An antibody Fc fragment that blocks IgG recycling and increases clearance of disease-causing antibodies
Myasthenia gravis (MG) has an estimated incidence between 0.3 to 2.8 per 100,000 and UK prevalence is about 15 per 100,000. Younger patients are more likely to be female, however the sex ratio evens out with age and for older patients incidence in males is higher. Prevalence has increased with time due to declining mortality [3,4].
Myasthenia gravis with generalised muscle weakness (Myasthenia Gravis Foundation of America (MGFA) class II, III, IVa and IVb)
Intravenous infusion

Further information

Yes

Trial or other data

Jun 21 PIII ADAPT trial is published; efgartigimod was well tolerated and more efficacious vs. placebo (of 129 acetylcholine receptor antibody-positive patients, response in 68% vs 30% in cycle 1; respectively, OR 4.95; 95% CI 2.21–11.53, p<0.0001) [13].
Oct 20Additional data from the PIII ADAPT trial have been presented at the Myasthenia Gravis Foundation of America (MGFA) 2020 Virtual Scientific Session. 55.6% of efgartigimod-treated patients showed a five-point or greater improvement on the Myasthenia Gravis Activities of Daily Living score, and 50.0% had a six-point or greater improvement on the Quantitative Myasthenia Gravis score; 33.9% of efgartigimod-treated patients showed a nine-point or greater improvement on the QMG score vs. none on placebo [10].
May 20Positive topline results from its Phase III ADAPT clinical trial. In the trial, 67.7% of AChR-Ab+ pts receiving efgartigimod hit the primary endpoint vs. 29.7% of the placebo cohort. The primary endpoint was the percentage of responders on the Myasthenia Gravis Activities of Daily Living (MG-ADL) score among AChR-Ab+ generalised gMG pts. Responders were defined as having >2 point improvement on the MG-ADL score for >4 consecutive weeks.[7]
Jan 20PIII ADAPT study has finished recruiting; collection of primary outcome data on course to complete Jun 20 [5].
Mar 19The ADAPT follow-up study (NCT03770403) starts. This open-label study will recruit participants from the placebo-controlled phase to evaluate safety and tolerability up to one year; estimated primary completion is June 2021 [2].
Sep 18The ADAPT PIII study (NCT03669588) is a multi-national placebo-controlled fully-blinded trial involving MG patients (est. n=150) with generalised muscle weakness. Primary outcome measure is efficacy as assessed by the percentage of "Myasthenia Gravis Activities of Daily Living (MG-ADL) responders" in the acetylcholine receptor (AChR)-antibody (Ab) seropositive population at week 8, and estimated primary completion date is June 2020. The study is recruiting across North America, Europe, and Japan [2].

Evidence based evaluations

VyvgartMyasthenia gravis with generalised muscle weakness (Myasthenia Gravis Foundation of America (MGFA) class II, III, IVa and IVb) - new subcutaneous formulation

Information

Vyvgart
New formulation
argenx
argenx

Development and Regulatory status

None
Phase III Clinical Trials
Phase III Clinical Trials

Category

An antibody Fc fragment that blocks IgG recycling and increases clearance of disease-causing antibodies, co-formulated with ENHANZE (recombinant human hyaluronidase PH20) drug delivery technology.
Myasthenia gravis (MG) has an estimated incidence between 0.3 to 2.8 per 100,000 and UK prevalence is about 15 per 100,000. Younger patients are more likely to be female, however the sex ratio evens out with age. Diagnosis is made more often in the elderly in whom the sex ratio is roughly equal [1].
Myasthenia gravis with generalised muscle weakness (Myasthenia Gravis Foundation of America (MGFA) class II, III, IVa and IVb) - new subcutaneous formulation
Subcutaneous injection

VyvgartImmune thrombocytopenia (ITP)

Information

Vyvgart
Licence extension / variation
argenx
argenx

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials
Yes

Category

Efgartigimod binds to neonatal Fc receptor (FcRn) blocks IgG recycling (including disease causing autoantibodies) and increases IgG clearance, resulting in faster remission and drastically reduced length and seriousness of acute autoimmune crisis. [2]
In the UK ~3,000 to 4,000 of the population have ITP at any one time. In 2010-11 (www.hesonline.nhs.uk ), there were 7,622 hospital admissions in England for ITP, accounting for 8,291 bed days.
Immune thrombocytopenia (ITP)
Intravenous

VyvgartPemphigus

Information

Vyvgart
Licence extension/variation
argenx
argenx

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials

Category

First-in-class neonatal Fc receptor blocker. Efgartigimod alfa-fcab is a human IgG1 antibody fragment that binds to the neonatal Fc receptor (FcRn), resulting in the reduction of circulating IgG [1].
The pemphigus family are rare autoimmune blistering diseases affecting the skin and mucous membranes. The four major entities of the pemphigus group include pemphigus vulgaris, pemphigus foliaceus, immunoglobulin A (IgA) pemphigus, and paraneoplastic pemphigus. Pemphigus vulgaris represents the most common form of pemphigus, but is still classed as a rare disease. Annual incidence of pemphigus vulgaris worldwide ranges from 1/143,000 to 1,430,000 [2-4].
Pemphigus
Subcutaneous

VyvgartChronic inflammatory demyelinating polyneuropathy (CIDP)

Information

Vyvgart
Licence extension/variation
argenx
argenx

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials
Yes

Category

A human IgG1 antibody Fc fragment developed for the treatment of IgG-mediated autoimmune disorders. Binds to the neonatal Fc receptor (FcRn) utilising the ENHANZE® subcutaneous delivery technology, resulting in the reduction of circulating IgG [3].
CIDP is a rare disorder that can affect any age group and the onset of the disorder may begin during any decade of life. CIDP affects males twice as often as females and the average age of onset is 50. The prevalence of CIDP is estimated to be around 5-7 cases per 100,000 individuals [2].
Chronic inflammatory demyelinating polyneuropathy (CIDP)
Subcutaneous