Biotech heads towards big catalysts
The second quarter promises big data reveals for Fibrogen, Travere, Argenx and Bavarian Nordic.
Following our analysis of key upcoming data for big pharma, Evaluate Vantage continues with a look at the important clinical results expected for biotech companies with a market cap of at least $1bn.
Fibrogen is hoping to make a mark in idiopathic pulmonary fibrosis with pamrevlumab, while Travere is gearing up to release longer term data on Filspari in focal segmental glomerulosclerosis. Elsewhere, Argenx will report data on its subcutaneous version of Vyvgart in an important new commercial opportunity for the anti-FcRn class, while Bavarian hopes to follow big pharma into the respiratory syncytial virus vaccine space.
Fibrogen’s chance in IPF
Pamrevlumab, Fibrogen’s antibody against connective tissue growth factor has two pivotal readouts due in the next quarter, in Duchenne muscular dystrophy and idiopathic pulmonary fibrosis, although data in the latter setting are the bigger focus. Results from the phase 3 study Zephyrus-1 are due on the primary measure of change in forced vital capacity (FVC) against placebo.
Roche’s Esbriet and Boehringer’s Ofev, both of which anti-fibrotics, are the only FDA approved treatments for IPF. Aside from limited efficacy, gastrointestinal side effects including diarrhoea and nausea are major limitations to use.
In phase 2 pamrevlumab hit its primary endpoint, significantly reducing the decline in FVC versus placebo. According to analysts at Cowen, physicians want to see a 39% delta between the trial's arms on reduction in FVC decline in Zephyrus-1.
Pamrevlumab could have a tolerability advantage over Esbriet and Ofev, with 16% of treated patients experiencing diarrhoea versus 8% on placebo in the earlier study. The larger phase 3 study will be a test of whether this rate continues.
Third time’s the charm?
Travere’s sparsentan, now branded Filspari, recently gained an accelerated FDA approval in IgA nephropathy, and data are now expected in another kidney disorder, focal segmental glomerulosclerosis (FSGS).
Filspari is a dual endothelin and angiotensin II receptor antagonist. Travere has twice tried to file for accelerated approval in FSGS, and failed both times. The initial filing was based on proteinuria data and the second, based on data from the phase 3 Duplex study, included an initial look at the slope of estimated glomerular filtration rate (eGFR), a harder endpoint.
Next quarter Travere expects to report two-year eGFR data from Duplex, versus irbesartan control. This could support a full approval.
Duplex has already shown a significant reduction in proteinuria, which Travere believes should translate into a significant treatment effect on eGFR. The company has noted that a ~0.75-1.0mL/min difference in the eGFR slope would be clinically meaningful.
Argenx’s next market
Argenx’s Vyvgart is already approved in myasthenia gravis as an intravenous therapy, and data on a subcutaneous version of the same active ingredient efgartigimod in a potentially large new setting – chronic inflammatory demyelinating polyneuropathy – are on the horizon.
The outcome to look for from Argenx’s Adhere study is the time to first relapse, as measured by a disability score called INCAT. Subcutaneous efgartigimod will have to look as good as intravenous immunoglobulins, the standard of care in CIDP, which have improved relapse rates by 24-37% over placebo.
However, to grab real share in this established market subcutaneous efgartigimod needs to offer an efficacy advantage over immunoglobulins. The anti-FcRn space is highly competitive, and Argenx needs this win to stay ahead.
Behind the rest in RSV
Bavarian Nordic has a lot of catching up to do in RSV. Both Pfizer and GSK have had positive FDA adcoms with their projects, both of which have Pdufas set for May. Moderna is due to file its candidate soon and J&J is also expected to report data in the second quarter.
Bavarian's phase 3 Vanir study tests MVA-BN RSV in 20,000 adults aged 60 and older and the primary measure is rate of lower respiratory tract disease compared with placebo.
The bar has been set by Moderna’s mRNA-1345 showing efficacy of 83.7%, which on a cross-trial basis looks competitive with GSK’s Arexvy and Pfizer’s Abrysvo vaccines. On safety both GSK and Pfizer’s FDA panels brought up cases of Guillain-Barré syndrome, which will be managed by postmarketing or pharmacovigilance efforts.
Even if MVA-BN RSV proves as good as the rest Bavarian might be fourth or fifth to market, which could make it tough to compete.
The table below contains a fuller list of upcoming catalysts with consensus forecasts from Evaluate Pharma.
|Big biotech's Q2 clinical catalysts|
|Product||Company||Therapy area||Q2 clinical catalyst||2028e indication sales ($m)||Note/Vantage coverage|
|Subcutaneous efgartigimod||Argenx||CIDP||Ph2 registrational Adhere||1,513||See text and Argenx's big bid to stay ahead|
|Domvanalimab +/- zimberelimab +/- etrumadenant||Gilead/Arcus||1st-line NSCLC (≥50% PD-L1)||Ph2 Arc-7 at Asco||905||Tigit project, more mature PFS expected, earlier look was positive but clinically disappointing (Three Tigit players look to surprise in 2023)|
|Filspari (sparsentan)||Travere||Focal segmental glomerulosclerosis||Pivotal Ph3 Duplex, 2 year eGFR data||302||See text|
|MORF-057||Morphic||Ulcerative colitis||Ph2 Emerald-1 open-label||284||See Morphic looks to justify “oral Entyvio” excitement|
|ARO-ANG3||Arrowhead||Mixed dyslipidemia, homozygous familial hypercholesterolemia||Ph2 Arches-2, Gateway (HoFH)||257||Anti-angiopoietin-like 3 RNAi therapeutic; Regeneron's Evkeeza, a MAb, is approved in HoFH|
|Alnylam||Hypertension||Ph2 Kardia-1 mid year (monotherapy)||218||SubQ RNAi therapeutic targeting liver-expressed angiotensinogen, admin quarterly and biannually, data from add-on study Kardia-2 at YE|
|Vatiquinone||PTC Therapeutics||Friedreich ataxia||Ph3 Move-FA||100||15-lipoxygenase inhibitor, Reata's Skyclarys (Nrf2 activator) was recently approved in the setting|
|Chronic graft versus host disease, 2L+ setting||Pivotal Agave-201 mid year||91||Anti-CSF1R monoclonal antibody, generated positive data at Ash 2021 (68% ORR at pivotal doses) in heavily pre-treated (3L+) chronic GvHD|
|AXS-12 (reboxetine)||Axsome||Narcolepsy||Ph3 Symphony||57||Oral norepinephrine reuptake inhibitor, narcolepsy marketed dominated by Jazz and Harmony Biosciences|
|PTC518||PTC Therapeutics||Huntington's disease||Ph2 Pivot-HD 12-week biomarker and safety data||13||Small-molecule RNA splicing modulator|
|MVA-BN RSV||Bavarian Nordic||RSV (adults ≥60)||Ph3 Vanir mid year||-||See text|
|Pamrevlumab||Fibrogen||Non-ambulatory Duchenne muscular dystrophy patients, idiopathic pulmonary fibrosis||Ph3 Lelantos-1 (DMD, Q2), Ph3 Zephyrus-1 (IPF, mid year)||-||See text for IPF; DMD study Lelantos-1 primary is functional assessment, secondary includes change in forced vital capacity|
|Vax-24||Vaxcyte||Pneumococcal vaccine (adults aged 65 and over)||Ph2 vs. Prevnar 20, topline safety, tolerability and immunogenicity||-||24-valent vaccine; GSK bought Affinivax for its early stage 24-valent vaccine|
|Fibrogen||Anaemia in lower risk myelodysplastic syndrome (MDS)||Ph3 Matterhorn||-||Last chance to salvage something for roxa, in the US (Pressure piles up on pamrevlumab)|
|CIDP: Chronic inflammatory demyelinating polyneuropathy. Sources: Evaluate Pharma, analyst notes, clinicaltrials.gov.|