Upcoming events – Wave takes on Huntington's and Argenx goes subcutaneous

After a delay Wave will finally see data for its Huntington's disease projects while Argenx's subcutaneous efgartigimod needs to keep the competition at bay.

Welcome to your weekly roundup of approaching clinical readouts. Most investor interest in Wave Life Sciences is centred around the Duchenne muscular dystrophy product suvodirsen, but a lot is also riding on the outcome of phase I/II trials for the Huntington’s disease assets WVE-120101 and WVE-120102.

Positive results could see Takeda exercise an option to develop the assets. But the road so far has not been smooth, as earlier this year Wave shares fell almost 20% after results from the two trials were delayed by slow patient enrolment.

Data on WVE-120102 are now due by the end of this quarter, with WVE-120101 results expected early next year. While the trials have been primarily designed to look at safety and tolerability, measurements will also include changes in huntingtin (HTT) protein. Secondary endpoints of functional changes as measured by the unified Huntington’s disease rating scale will be examined for early signs of disease modification, although this data won't be available by the end of the year.

Wave’s two antisense oligonucleotides bind HTT mRNA, preventing production of the mutant protein that lies behind Huntington's disease, but the company is not alone in tackling this disorder.

Roche and Ionis’s RG6042 is in the pivotal Generation-HD1 trial, and could be filed in early 2020. This project knocks out healthy and mutant forms of the HTT gene alike, and Wave hopes that leaving healthy HTT alone might prove a safer bet, as the long-term effect of knocking out expression of the wild-type HTT gene is unknown.

Antisense treatments might eventually come under pressure if Uniqure finds success with its Huntington's gene therapy AMT-130, which is due to start a phase I/II trial early next year. The Huntington’s market could be big enough for multiple therapies, but Wave will want to avoid any more delays and to be second, rather than third, to market.  

Antisense and gene therapy for Huntington's disease
Status Project Mechanism of action Company

2024e sales ($m)

Clinical trials
Phase III RG6042 HTT antisense Roche/Ionis 398 Generation-HD
Phase I/II WVE-120101 HTT SNP1 antisense Wave Life Sciences/Takeda 93 Precision-HD1
  WVE-120102 HTT SNP2 antisense Wave Life Sciences/Takeda 70 Precision-HD2


AMT-130 AAV5 vector carrying micro-RNA to silence HTT Uniqure 68 NCT04120493
HTT=Huntingtin. Source: EvaluatePharma & clinicaltrials.gov.

Subcutaneous key

Meanwhile, with Argenx’s lead in targeting the neonatal Fc receptor (FcRn) hanging by a thread the company needs to show that its latest subcutaneous formulation of efgartigimod can deliver. Argenyx is using an IV form in pivotal trials, but a SC version is a must-have if the project is to gain ground in chronic autoimmune disorders.

A phase I study of SC efgartigimod is due to report before the end of the year. The project uses Halozyme’s Enhanze technology, and needs to show non-inferiority to, and potentially interchangeability with, the IV formulation on the primary endpoint of IgG levels after 11 weeks' treatment. 

Efgartigimod, an antibody fragment, works by binding to FcRn, which controls the breakdown of IgG. Reducing the levels of IgG circulating in the body is the goal of treatments for IgG-mediated autoimmune diseases like myasthenia gravis and immune thrombocytopenia.

The phase I results will define Argenx's commercial plans, including potential bridging from later-stage IV studies, which could speed up the SC project's clinical development. 

Argenx signed an exclusive license with Halozyme back in February for $30m upfront, preventing other competitors from collaborating with Halozyme. Argenx also has its own SC form, not subject to the Halozyme deal, but this is designed for maintenance dosing.

Competition in the FcRn space is not far behind, so Argenx cannot afford to slip up. UCB’s whole antibody rozanolixizumab is delivered SC, although as an infusion rather than an injection like efgartigimod. Rozanolixizumab is in phase III trials for myasthenia gravis, and phase II results are due at Ash in primary immune thrombocytopenia.

Efgartigimod has an NPV of $4.4bn, according to EvaluatePharma, nearly matching Argenx's $4.9bn market cap. The Dutch biotech also has plenty of cash, having ended the third quarter with €923.2m ($1.02bn) in the bank and recently topped this up with a equity raise that brought in a further $557m.

Targeting FcRn
Status Project Company 2024e sales ($m) Administration Upcoming SC data
Phase III Efgartigimod Argenx 988 IV, SC and SC with Enhanze PhI data healthy volunteers due YE 2019
  Rozanolixizumab UCB 135 SC PhIII gMG due H1 2021
Phase II Nipocalimab Momenta  55 IV, SC planned -


4 IV, SC planned PhII gMG planned H2 2020
  IMVT-1401 Immunovant - SC PhII Graves' ophthalmopathy due Q1 2020
PhII gMG due Q2 2020
Phase I ABY-039 Alexion/Affibody - SC PhI healthy volunteers due H1 2020

IV=intravenous; SC=subcutaneous, gMG=generalized myasthenia gravis. Source: EvaluatePharma, Credit Suisse & clinicaltrials.gov.

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