Argenx takes a step towards convenience
The group is taking a subcutaneous formulation of efgartigimod to regulators, but is keeping quiet about price.
Last year Argenx bagged approval for the first FcRn antagonist, efgartigimod, trademarked as the intravenously delivered Vyvgart. Now a subcutaneous version is heading to regulators by year end, following success in the pivotal Adapt-SC trial in generalised myasthenia gravis.
There are some lingering questions about the incidence of adverse events with the subcutaneous formulation. But assuming that these will not worry the FDA, the big unknown at present is how Argenx will choose to price this more convenient option – something that, for now, it will not discuss.
New brand, new price?
Argenx’s chief operating officer, Keith Woods, noted during a conference call today that, as the subcutaneous formulation was created with Halozyme’s delivery technology, it would be classed as a completely different product to Vyvgart in the US – with a different BLA, brand name and, perhaps, price.
Although he said the company had not yet decided on cost, he highlighted a scenario in which a subcutaneous drug administered at home could be priced higher than the typical $225,000 a year for the intravenous formulation, but still be cheaper for healthcare systems by sidestepping the need for patient visits and nursing time.
He emphasised that Argenx would market both options, to give patients choice. He said some patients would not want to self-administer, so might prefer the intravenous version; meanwhile, for others, the speed of the subcutaneous version, which takes around 30 seconds to deliver, would win out.
Argenx believes that around 70% of generalised myasthenia gravis (GMG) patients will plump for subcutaneous efgartigimod and 30% for Vyvgart, based on their own market research. The group is also trialling efgartigimod, both intravenous and subcutaneous, in a raft of other indications.
|Approaching clinical readouts for Argenx and efgartigimod|
|Adapt-SC||Head-to-head trial of SC vs IV in GMG||Positive topline data Mar 2022|
|Adapt-SC+||Long-term safety study of SC formulation in GMG||Completes Apr 2023|
|Advance||Pivotal trial of IV formulation in ITP||Topline data due Q2 2022|
|Advance-SC||Pivotal trial of SC formation in ITP||Topline data due Q1 2023|
|Advance-SC+||Long-term safety study of SC formulation in ITP||Completes Oct 2026|
|Adhere||Phase 2 trial of SC formulation in CIDP||Topline data due Q1 2023|
|Adhere+||Long-term safety study of SC formulation in CIDP||Completes Sep 2024|
|Address||Pivotal trial of SC formulation in pemphigus||Under review owing to events in Ukraine|
|Address+||Long-term safety study of SC formulation in pemphigus||Completes Aug 2023|
|Note: CIDP=chronic inflammatory demyelinating polyneuropathy; GMG=generalised myasthenia gravis; ITP=immune thrombocytopenia; IV=intravenous; SC=subcutaneous. Source: Evaluate Pharma, clinicaltrials.gov & company statements.|
In GMG, at least, the path forward is now clear. Adapt-SC met its primary endpoint, showing that subcutaneous efgartigimod was non-inferior to Vyvgart on total IgG reduction from baseline at day 29.
This is a proxy for efficacy, and Argenx says it has buy-in from the FDA on this bridging strategy.
Adapt-SC also showed a comparable performance with the subcutaneous and intravenous formulations on measures of clinical efficacy, which were secondary endpoints.
However, the incidence of adverse events raised eyebrows, with analysts on today’s call flagging injection site reactions and the fact that more patients in the subcutaneous arm experienced a rebound in GMG symptoms. Argenx execs stressed that 18 of 21 injection site reactions were mild, and the rest resolved after treatment with local steroids and antihistamines.
On GMG rebound, Argenx’s chief executive officer, Tim Van Hauwermeiren, said cases typically happened towards the end of the follow-up period and that this was to be expected given that patients only received a single treatment cycle in the trial – for both formulations this involves four weekly doses.
When asked about the discrepancy between the arms, he replied that it was up to physicians whether or not to report worsening symptoms. Another explanation could be that IgG rebound appeared to occur slightly sooner with the subcutaneous versus intravenous formulations, something that could be solved by earlier retreatment with the former.
Argenx is testing repeat dosing, on an as-needed basis, in the Adapt-SC+ long-term safety study. It has a priority review voucher, but has not yet decided whether to use this for subcutaneous efgartigimod.
As for the anti-FcRn competition, UCB’s rozanolixizumab, which is infused subcutaneously over one to two hours, recently hit in the pivotal MycarinG in GMG, but full results are not yet available. Johnson & Johnson has an intravenous project, nipocalimab, in a phase 3 GMG trial that is set to complete in 2024.
|Subcutaneous vs intravenous efgartigimod: results from the Adapt-SC study|
|Mean total IgG reduction from baseline at wk 29*||66.4%||62.2%|
|Minimal symptom expression||37.0%||38.2%|
|Pts with ≥grade 3 AE||16.4%||7.3%|
|Injection site reactions||38.2%||1.8%|
|Myasthenia gravis symptoms||10.9%||1.8%|
|*Primary endpoint; MG-ADL responder: ≥2-point reduction ≥4 consecutive weeks during the first cycle; QMG responder: ≥3-point reduction for ≥4 consecutive weeks during the first cycle; MSE: MG-ADL score of 0 or 1. Source: company presentation.|