Anaphylaxis: the Darth Vader of allergies

EU Clears AstraZeneca's New-form Severe Asthma Drug Tezspire

AstraZeneca's first-in-class severe asthma therapy Tezspire has been approved in the EU in a new pen injector formulation suitable for administration by patients themselves.

The green light for the pre-filled, single-use pen version of Tezspire (tezepelumab) comes just four months after the TSLP inhibitor became the first biologic therapy for severe asthma to be cleared in the EU for use in all patients, and not restricted to those with forms of the disease tied to specific characteristics such as high levels of eosinophils.

AZ's head of biopharma R&D Mene Pangalos said the new device would help support the use of Tezspire to treat "a broad population of severe asthma patients." It is estimated that there are 2.5 million patients worldwide with severe asthma who are uncontrolled, without any phenotypic and biomarker limitation.

At the moment the biologic is delivered as a pre-filled syringe (pictured above) that is dosed once a month by a healthcare worker, but the new formulation will allow patients to take greater control of their treatment.

Like its predecessor, it is approved in the EU for use in patients 12 years and older with severe asthma who are inadequately controlled with high dose inhaled corticosteroids plus another medicinal product.

The new version has been authorised on the back of the phase 1 PATH-BRIDGE and phase 3 PATH-HOME studies, which showed that 92% of healthcare providers, patients, and caregivers were able to successfully administer it, with no loss of efficacy compared to the approved formulation.

Analysts have suggested that Tezspire could become a $1 billion-plus product, thanks to its ability to be prescribed across the board in eligible severe asthma patients.

That gives it an advantage over other biologics for severe asthma, such as Sanofi/Regeneron's IL-4/IL-13 inhibitor Dupixent (dupilumab) and AZ's IL-5 inhibitor Fasenra (benralizumab) - which competes with GlaxoSmithKline's Nucala (mepolizumab) and Teva's Cinqaero (reslizumab), which have restrictions on their use.

The EU approval for the pen injector has come ahead of the US, where Tezspire has been sold by AZ's partner Amgen since the start of 2022. Uptake in the US has exceeded expectations, with Amgen reporting $55 million in sales in the third quarter of 2022, taking its tally for the first nine months to $91 million.

That suggests Tezspire will more than double predictions for 2022 sales of around $50 million from analysts at Piper Sandler, who reckoned 2023 sales would quickly rise to $500 million.

The strong US sales have come despite a list price of around $47,000 per year ahead of discounts or rebates, well above a "placeholder" price of $28,000 that the Institute for Clinical and Economic Review (ICER) said would be too high to be cost-effective in a pre-approval report.

AZ said it expects a regulatory decision by the FDA on the pre-filled pen in the first half of 2023.

The approval came as AZ revealed it was pulling another product from the market in the US – hairy cell leukaemia therapy Lumoxiti (moxetumomab pasudotox) after four years. The decision was taken in the face of low clinical uptake that the company has attributed to complex administration and a demanding regimen to prevent toxicity and monitor patients.

The Unmet Need In T2-low Asthma: A Critical Gap In Treatment

Severe asthma is traditionally classified into either high or low T-helper cell type 2 (T2) subtypes. T2-high asthma, which is characterised by allergic inflammation and elevated eosinophil levels, has seen significant advances in treatment and disease management with the advent of biological therapies. However, T2-low asthma, which lacks the characteristic biomarkers that are associated with T2-high asthma, remains underdiagnosed and underserved. Experts interviewed by leading data and analytics company GlobalData emphasise the challenges in diagnosing T2-low asthma due to the absence of reliable biomarkers, leading to delayed treatments for many patients. Recent studies have shown the need for better diagnostic tools, as current methods fail to distinguish T2-low asthma from other forms, hindering effective treatment decisions (Kankaanranta, 2023).

Although biologic therapies have revolutionised the treatment of T2-high asthma, T2-low asthma remains largely neglected. Many key opinion leaders (KOLs) interviewed by GlobalData stressed the lack of biologic therapies specifically targeting T2-low asthma. Current biologic treatments focus primarily on eosinophilic or allergic inflammation, leaving patients with non-eosinophilic or neutrophilic asthma with limited options. In the broader treatment landscape, competitors such as Areteia Therapeutics' dexpramipexole, which has potential applications beyond eosinophilic asthma, and AstraZeneca's Breztri, currently approved for chronic obstructive pulmonary disease but being explored for asthma, are noteworthy. Additionally, Sanofi's dual interleukin-13 and thymic stromal lymphopoietin antibodies have garnered attention for their potential to address complex asthma phenotypes, including T2-low cases. As such, advanced strategies such as multi-omics analyses and precision medicine, hold promise for identifying novel therapeutic targets, offering the potential to significantly improve outcomes for this underserved group (Fouka et al, 2022).

A significant barrier to effective treatment is the diagnostic challenge. In Japan, experts note that biomarkers such as eosinophils and immunoglobulin E are commonly used to diagnose asthma subtypes, but these markers are ineffective for diagnosing T2-low asthma, complicating early detection. It has also been noted that without reliable biomarkers, many patients with T2-low asthma remain undiagnosed and untreated (Kankaanranta, 2023). As asthma prevalence continues to rise globally- particularly in regions with high pollution - the urgency for more accurate diagnostic tools and therapies becomes clear.

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Along with diagnostic hurdles, treatment adherence remains a significant challenge. One US KOL notes that despite the availability of biologics, adherence is often compromised by issues such as inhaler technique, high medication costs, and inconsistent use. This aligns with findings indicating widespread inhaler misuse, where many patients fail to use their medications correctly despite multiple instructions. Improving patient education on proper inhaler use and ensuring better access to treatments are essential to enhancing asthma control and preventing exacerbations.

In conclusion, T2-low asthma represents a critical unmet need in asthma management. Despite significant progress in treating T2-high asthma, patients with T2-low asthma continue to lack effective therapies. More research is needed to identify reliable biomarkers and develop targeted treatments for this population. Additionally, enhancing diagnostic methods, improving patient education, and increasing adherence to treatments will be essential for improving outcomes for all asthma patients, particularly those with T2-low asthma.

"The unmet need in T2-low asthma: A critical gap in treatment" was originally created and published by Pharmaceutical Technology, a GlobalData owned brand.

 

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New Nasal Swab Test Holds Promise For Asthma Treatment

Diagnosing precisely what type of asthma a child has and fine-tuning the treatment for it involves an invasive procedure under general anesthesia. For children with mild asthma, it's just not worth the risks involved – or even ethical – to put them through the procedure, according to clinicians in the field.

That is why a new nasal swab test that can identify a child's subtype of asthma may transform the way the disease is treated, according to the University of Pittsburgh researchers who developed it. 

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"Because asthma is a highly variable disease with different endotypes, which are driven by different immune cells and respond differently to treatments, the first step toward better therapies is accurate diagnosis of endotype," said Dr. Juan Celedón, chief of pulmonary medicine at UPMC Children's Hospital of Pittsburgh.

Asthma is the most common chronic childhood disease, affecting approximately 1 in 10 children, according to the National Institutes of Health. The disease, which has no cure, causes airways to constrict and sometimes produces excess mucus. It is generally classified as T-2 high, T-17 high and low low, based on cells that cause inflammation.

Celedón and his team collected nasal samples across three studies from 459 Puerto Rican and Black children, who have higher rates of asthma and are more likely to die from it than white children due to social inequities caused by structural racism, according to the Asthma and Allergy Foundation of America.

The study, published Thursday in JAMA, found that 23% to 29% of the children had the T2-high subgroup, 35% to 47% had T17-high and 30% to 38% had low-low.

A potent type of new drugs called biologics target the immune cells that drive T2-high asthma, but no such medication exists for the other subgroups of the disease. The nasal swab test may now spur other areas of asthma research, Celedón said.

"One of the million-dollar questions in asthma is why some kids get worse as they enter puberty, some stay the same and others get better," Celedón said. "Before puberty, asthma is more common in boys, but the incidence of asthma goes up in females in adulthood. Is this related to endotype? Does endotype change over time or in response to treatments? We don't know. But now that we can easily measure endotype, we can start to answer these questions."

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