Exton, Pennsylvania, Aug. 15, 2023 (GLOBE NEWSWIRE) -- Since launching in May 2022, Sanofi/Regeneron’s Dupixent has been well received by gastroenterologists and allergists as an advancement for treating eosinophilic esophagitis (EoE). More than two-thirds of doctors view the IL-4 inhibiting biologic as a significant advancement for the treatment of EoE and three-quarters of doctors express high satisfaction with the clinical improvement they observe in their Dupixent-treated patients (Launch Dynamix™: Dupixent in Eosinophilic Esophagitis (US)).
Moreover, Dupixent continues to enjoy a unique position as the only advanced treatment for EoE. Several promising biologic challengers struggled in clinical trials, failing to achieve significant improvement in dysphagia, the most burdensome and common symptom of EoE. Trials for AstraZeneca’s Benralizumab, Allakos’ lirentelimab, GSK’s mepolizumab, and BMS’ cendakimab each yielded similar clinical results - reducing eosinophil counts - but missing endpoints in varying degrees on symptom reduction. Of the four, only cendakimab remains listed on the manufacturer’s pipeline.
Consequently, an unlikely candidate has emerged as the next significant advancement in EoE, potentially landing the coveted second-to-market position. APT-1011, a reformulation of the commonly used EoE treatment fluticasone, achieved significant improvements in both histologic and symptomatic endpoints. The combination of unmet patient needs and APT-1011 clinical effectiveness was sufficient to warrant Fast Track designation from the FDA in 2021.
Despite the promising position, Spherix found over two-thirds of gastroenterologists and allergists are not familiar with the emerging therapy, and only one-third stated a high likelihood to prescribe the medication when shown the clinical data. A somewhat surprising finding as Spherix noted earlier this year that gastroenterologists expressed equal enthusiasm for new steroid formulations as they did for new biologics for the treatment of EoE (Market Dynamix™: Eosinophilic Esophagitis (US) – 2022).
While not considered a direct competitor to biologics, APT-1011’s unique formulation of the “old dog,” fluticasone, improves delivery of the medication, providing better adhesion to the esophagus and limiting systemic absorption. This “new trick” comes courtesy of the drug’s origin from Adare Pharmaceutical Solutions, which developed AdvaTab®, a proprietary technology for patients who experience difficulty swallowing. While APT-1011 is easy to swallow, the more interesting characteristic is the effect on systemic absorption.
Published data showed:
Pharmacokinetic of APT-1011, both from a phase 1 study and from the phase 2b study, show picograms per mL levels in plasma, well below those associated with systemic side effects and suppression of endogenous cortisol.
The clinical implication is APT-1011 potentially eliminates systems risks associated with chronic corticosteroid use, such as hypertension, acne, water retention, glaucoma and others.
Speaking with physicians in depth, Spherix explored the benefits and implications of APT-1011 when compared to the gold standard EoE treatment, Dupixent. Both gastroenterologists and allergists, unsurprisingly, raised the common metaphor of shotguns and rifles when comparing the two – steroids being an agent that broadly suppresses immune function (shotgun), while Dupixent specifically targets the IL-4 immune pathway (rifle). A complimentary perspective for doctors to consider examined the local vs. systemic attributes for each. APT-1011 offers locally acting, broadly suppressing treatment, whereas Dupixent offers systemically acting, targeted suppression.
When pressed on the choice, doctors agreed the targeted nature of biologics are still conceptually preferred where chronic treatment is required. Whether locally acting or broadly, chronic use of steroids to suppress immune function comes with risk. As one physician states:
“corticosteroids are a wonder drug, but it’s a wonder anybody uses it, because there really is so many adverse effects” – US gastroenterologist
More specifically, an allergist noted the complexity of the immune system, discussing the various cells and signaling involved and highlighting instances where suppression could be unhelpful:
“you need those things [fibroblasts]. They’re everywhere and they repair tissue, take care of tissue. They don’t seem to be dysfunctional. They’re just doing their job” – US Allergist
However, when reviewing data from APT-1011s FLUTE trial, doctors broadly agreed the drug will play an important role in EoE treatment if approved. While the concept of locally acting, broad spectrum treatment vs. system targeted treatment was intellectually interesting, doctors emphasized the decision to use the drug (and all drugs) is predicated on the clinical data. Having reviewed the FLUTE data, each was sufficiently comfortable that the risk benefit profile is adequate to warrant use.
When pressed where APT-1011 fits in the treatment pathway, no definitive placement was agreed. Rather three principles will influence choice: the published APT-1011 clinical data, patient clinical presentation, and patient preference. Arguments were made to use of APT-1011 ahead of Dupixent (similar to today’s guidelines), after Dupixent, or in combination with the biologic.
The net findings from Spherix are both Dupixent and APT-1011 provide physicians with unique and differentiated tools to help EoE patients manage their condition. The addition of APT-1011 will likely increase the number of patients being treated overall, offering a more convenient alternative to today’s off-label steroid choices. Which patients will be treated with one of the two advanced options will ultimately be driven by individual patient need and situation.
Spherix plans to further research real world EoE treatment behavior as evidenced in patient medical charts (RealWorld Dynamix™: Eosinophilic Esophagitis (US)) later this year, including clarifying patient cohort characteristics associated with current and future treatments. Should APT-1011 receive FDA approval, Spherix will track the launch for 18 months through the launch service (Launch Dynamix™: APT-1011 (Ellodi) in Eosinophilic Esophagitis (US)).
About Launch Dynamix™
Launch Dynamix™ is an independent service providing a monthly benchmarking of newly launched products for the first eighteen months of commercial availability, augmented by a quarterly deep dive into patient types initiated, brand perceptions, promotional activity, and drivers and barriers to uptake.
About Market Dynamix™
Market Dynamix™ is an independent, subscription-based service that explores future dynamics of evolving healthcare markets within specific indications to help your company make well-informed, strategic decisions. The Spherix research method pairs together both qualitative analyses, fueled by interviews with leading international opinion leaders, and quantitative analysis, leveraging a proprietary network of specialists "in the trenches."
RealWorld Dynamix™
RealWorld Dynamix™ is an independent, data-driven service unveiling real patient management patterns through rigorous analysis of large-scale patient chart audits. Insights reveal the “why” behind treatment decisions, include year over year trending to quantify key aspects of market evolution, and integrate specialists’ attitudinal & demographic data to highlight differences between stated and actual treatment patterns.
About Spherix Global Insights
Spherix Global Insights is a leading provider of market research, business intelligence and advisory services to the global life sciences industry. The company's unique service offerings are powered by deep therapeutic knowledge, the Spherix Network specialty physician panel, and commercially relevant analyses to enable strategic decision-making by our valued customers.
A trusted advisor and industry thought leader, Spherix Global Insights provides specialized market expertise in six (6) focused therapeutic areas including: dermatology, gastroenterology, nephrology, neurology, rheumatology and ophthalmology.
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