Biotechnology

Arrowhead Pharma therapy shows promising results for asthma


Arrowhead Pharmaceuticals Inc. have announced interim results from the ongoing phase 1/2 clinical study ARO-RAGE, an investigative RNA interference therapy (RNAi) designed to reduce receptor production for advanced glycation end products (RAGE) as a potential treatment for inflammatory lung diseases, such as asthma.

These data represent the first clinical demonstration of the potential utility of Arrowhead Pharmaceuticals’ targeted RNAi (TRiM) molecular platform optimized for lung delivery.

Matthias Salathe, professor, Pulmonary, Critical Care and Sleep Medicine, and Vice-Chancellor for Research at the University of Kansas Medical Center, said: “These interim data for phase 1/2 ARO-RAGE are very encouraging. An unmet need continues to exist for the many patients with severe asthma who suffer persistent symptoms and exacerbations, despite current therapy.

“Reducing RAGE protein expression in lung epithelial cells to levels demonstrated by ARO-RAGE to date in this study has the potential to treat patients with asthma and other inflammatory lung diseases in completely new ways. RAGE represents a promising target for intervention because its activation has been implicated as a proximal regulator of the inflammatory cascade in the asthmatic airway, and thus silencing RAGE can produce potent anti-inflammatory effects. I look forward to the availability of additional results from this important trial.”

Arrow Medicine‘ learning outcomes

Interim results of ARO-RAGE administration in part 1 of an ongoing phase 1/2 study in normal healthy volunteers include: reduced soluble RAGE (sRAGE) measured in serum after two doses on day 1 and day 29, maximum reduction in mean the mean maximum reduction at the 92 mg dose was 80% with a maximum reduction of 90%, and the mean maximum reduction at the 10 to 44 mg dose level showed a dose response ranging from 31% to 59%.

The results also demonstrated that the duration of the pharmacological effects lasted at least 6 weeks after the second dose of 92 mg. The average reduction at the 92 mg dose was 75% with a maximum reduction of 92%, while the average reduction at the 10 to 44 mg dose ranged from 44% to 52%. A reduction in serum sRAGE was also observed after a single dose.

The average maximum reduction at the 92 mg dose was 56% with a maximum reduction of 68%, and the average maximum reduction at the dose level of 10 to 44 mg showed a dose response and ranged from 23% to 53%. No serious or severe side effects have been reported. Data are not yet available for single or multiple dose cohorts at 184 mg, the highest dose being tested.

Christopher Anzalone, president and CEO at Arrowhead Pharmaceuticals, said: “We think this interim data with ARO-RAGE represents clinical validation of Arrowhead’s inhaled lung TRiM platform and, in particular, ARO-RAGE as a potential new therapy to treat patients with pneumonia. . disease. High levels of target gene knockdown, long duration of effect, and promising safety and tolerability results are all very encouraging signs for the growth path of our RNAi therapy candidates utilizing this same platform. We look forward to providing additional data at the upcoming R&D Day on June 1, 2023, and at future medical appointments.”

Earlier this year, AstraZeneca’s Airsupra received US approval as a new rescue treatment for asthma. Another company tackling asthma is a startup, Upstream Bio, which last year announced a trial to develop a new long-acting asthma treatment.

About RAGE

RAGE is involved in the pathogenesis of various inflammatory diseases, including asthma. Reduction of RAGE expression via RNAi was designed to reduce the amount of RAGE protein expressed on lung epithelial cells. Reduced RAGE expression in the lung epithelium may result in reduced RAGE-dependent inflammatory pathways, leading to decreased exacerbation frequency and increased airflow in asthmatic patients.



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