Upstream Bio’s stock value took a 47% downturn following the debut of topline results from a Phase II trial on its lead candidate, verekitug in severe asthma.
The therapy met its primary trial endpoint in the ongoing VALIANT study (NCT06196879) by demonstrating a 56% reduction in the rate of yearly asthma flare-ups compared with placebo in patients on a 12-week, 100mg dosing schedule. This rate mirrors the 56% reduction in flares observed in the Phase III NAVIGATOR trial (NCT03347279) on AstraZeneca and Amgen’s marketed once-monthly therapy for severe asthma, Tezspire (tezepelumab). However, researchers have not conducted a head-to-head study.
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However, the the 400mg dose of verekitug given every 24 weeks did not match Tezspire’s disease-modifying activity in the NAVIGATOR trial, as patients only experienced a 39% decrease in asthma flare-ups at week 60. Tezspire led to an 0.93 annualised asthma exacerbation rate compated with 2.10 in the placebo group.
Pre-specified analyses of secondary outcomes at week 24 found that patients treated with verekitug, a thymic stromal lymphopoietin (TSLP) blocker, also experienced statistically significant improvements in forced expiratory volume in one second (FEV1) and exhaled nitric oxide (FeNO) compared with the placebo group. Both FeNO and FEV1 are key biomarkers for type-2 airway inflammation.
Verekitug was well tolerated across all active doses, with its safety profile remaining consistent with previous studies done on the subcutaneous therapy.
Despite the endpoint being met, investors were unconvinced with the topline data. Upstream’s share price dropped 47% from $27.81 at market close on 10 February to $14.69 at the same time the next. Upstream published the VALIANT data before market open on 11 February. Upstream’s market cap is $793.8m.
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By GlobalDataIn a research note, William Blair analyst Matt Phipps noted that investor feedback has primarily centred around the success of verekitug as a twice-yearly dosing option.
Phipps said: “The lower exacerbation reduction seen at 400mg Q6M has raised concerns on the competitive positioning of verekitug versus others in Phase II/III development. The onus is now on the competitors to demonstrate strong exacerbation reduction and symptom improvement at a Q6M dosing regimen”.
Next steps for verekitug
Following the VALIANT readout, Upstream plans to initiate registrational trials evaluating verekitug in both severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). These plans are pending next step discussions with regulators.
Upstream plans to present additional findings from the VALIANT study at a future medical conference.
Upstream is also looking to progress verekitug’s development in chronic obstructive pulmonary disease (COPD) through the Phase II VENTURE study, which has enrolled more than 60% of target patients, according to an 11 February statement.
Severe asthma’s market gap
In an investor call discussing the results, analysts were keen to know how verekitug may compare with other approved medications within the severe asthma indication – including blockbuster sellers Dupixent (dupilumab) and Tezspire.
When asked how verekitug may fit into the market, Upstream’s head of R&D and CMO, Aaron Deykin, noted that novel agents will likely be able to “come in and take substantial share – not by eroding the share of others, but by driving penetration”.
“We think it could break out in multiple ways; that could be total efficacy, eligible patient populations or patient convenience and dosing intervals,” Deykin said.
To achieve a high uptake amongst patients, verekitug will have to compete for market share with drugs like Dupixent and Tezspire.
While Dupixent’s sales figures may see a decline upon its loss of market exclusivity from 2030, GlobalData forecasts that the drug will generate peak sales of $25.7bn for Sanofi and Regeneron in 2030. GlobalData estimates that Tezspire will generate peak sales of $4.4bn for Amgen and AstraZeneca in 2031.
A recent report from GlobalData, parent company of Clinical Trials Arena, forecasts that the global severe asthma market will grow to $10.1bn by 2033.
