Arrowhead Pharmaceuticals Presents New Clinical Data Showing ARO-RAGE Achieves High Level of Gene Knockdown in Patients with Asthma
Arrowhead Pharmaceuticals announced interim clinical data for ARO-RAGE, an investigational RNAi-based medicine for inflammatory lung diseases like asthma. The data revealed significant reductions in soluble RAGE (sRAGE) levels in both bronchoalveolar lavage fluid (BALF) and serum among healthy volunteers and asthma patients. ARO-RAGE achieved up to 88% reduction in sRAGE in asthma patients after two doses, with sustained effects supporting bi-monthly dosing. The treatment demonstrated a favorable safety profile with no serious adverse effects. Additionally, Arrowhead presented promising preclinical results for therapies targeting thymic stromal lymphopoietin (TSLP) and influenza A viruses.
- ARO-RAGE reduced serum sRAGE by up to 88% in asthma patients.
- Data supports bi-monthly dosing due to long-lasting effects.
- ARO-RAGE showed a favorable safety and tolerability profile with no serious adverse effects.
- Significant reductions in sRAGE observed in both BALF and serum in healthy volunteers and asthma patients.
- ARO-RAGE plasma exposure was in quantity and duration.
- Promising preclinical data for therapies targeting TSLP and influenza A viruses.
- The data presented is interim and from an ongoing Phase 1/2 study, which means it is not yet conclusive.
- No detailed financial data or projected revenues from ARO-RAGE were provided.
- The success in preclinical stages for other projects does not guarantee similar results in clinical trials.
Insights
The interim clinical data on ARO-RAGE is noteworthy for its high level of gene knockdown in patients with asthma. This RNAi-based medicine, leveraging Arrowhead's TRiMTM platform, showed up to
The fact that the treatment demonstrated a long duration of effect and a favorable safety profile is crucial. Typically, asthma treatments like corticosteroids can have long-term side effects, so a new approach with a favorable safety profile could be a game-changer. The two-month dosing interval is also beneficial, potentially increasing patient compliance and convenience.
However, it is important to note that these results are from an early-stage trial, specifically a Phase 1/2 study, which means further research in larger, more diverse populations is necessary to confirm these findings. Investors should closely follow the progression into Phase 2 studies, as this will provide more robust safety and efficacy data.
For retail investors, the potential market impact of a successful asthma treatment cannot be understated. However, the journey from clinical trials to market approval is fraught with hurdles, so caution is advised.
Arrowhead Pharmaceuticals' presentation of new clinical data on ARO-RAGE could have a substantial impact on its stock price. The company's ability to achieve up to 88% reduction in serum sRAGE in asthma patients is a significant milestone. This achievement not only highlights the potential of ARO-RAGE but also reinforces the value of the TRiMTM platform.
From a financial perspective, the announcement could drive investor confidence, especially as the company prepares to initiate a Phase 2 study in late 2024. The long duration of effect and favorable safety profile are particularly attractive to investors looking for sustainable, long-term gains. Furthermore, the ability to dose every two months could lead to higher patient adherence, potentially translating into steady revenue streams.
It is essential to remain cautious, though. The biotech sector is known for its volatility, primarily due to the high-risk nature of clinical trials. While the data is promising, the transition from Phase 1/2 to Phase 2 will be critical. Investors should consider diversifying their portfolios to mitigate risks associated with the early stages of biotech development.
Investors should also pay attention to Arrowhead's cash burn rate and funding strategies as the company advances its pipeline. The current results are positive, but sustained financial health is key to long-term success.
- ARO-RAGE reduced serum sRAGE by up to
- Additional promising results presented on two preclinical stage programs targeting thymic stromal lymphopoietin (TSLP) and influenza A viruses
“These results underscore the potential of our proprietary TRiMTM platform to enable us to develop impactful new therapies to potentially treat multiple pulmonary diseases with significant unmet needs. Arrowhead was the first company to show that RNAi could be harnessed to achieve high levels of target gene knockdown in the lung in healthy human subjects and these data presented at ATS 2024 build on that success,” said James Hamilton, M.D., chief of discovery and translational medicine at Arrowhead. “Our ARO-RAGE data is first-in-class and demonstrated deep and sustained knockdown in the lung in patients with mild to moderate asthma, a long duration of effect that appears to support every two-month dosing, and a favorable safety and tolerability profile. These results give us further confidence as we move towards the initiation of a Phase 2 study in late 2024.”
Select ARO-RAGE Results
In the ongoing 1001 study, ARO-RAGE achieved the following key results as of 05 April 2024:
- Single and multiple doses of ARO-RAGE in NHVs led to dose dependent reductions in sRAGE in both BALF and in serum
-
After two doses of ARO-RAGE in patients with mild to moderate asthma, serum sRAGE was reduced up to
88% with a mean maximum reduction up to77% - Serum sRAGE was reduced in a dose-responsive manner with similar reductions observed in NHVs and patients with asthma at each dose level
- Pharmacodynamic effects were long lasting, with a duration that appears to support once every two-month dosing
- ARO-RAGE plasma exposure following a single dose in NHVs was of limited quantity and duration
Safety and Tolerability Results
ARO-RAGE has shown a favorable safety profile to date, with no demonstrated pattern of effect on systemic safety labs and no demonstrated pattern of detrimental effect on lung function (FEV1, FVC, or DLCO) over time. There have been no serious adverse effects related to study drug and no treatment emergent adverse events leading to trial withdrawal or study drug discontinuation.
Arrowhead also presented preclinical data on two additional lung targeted programs that utilize the company’s proprietary Targeted RNAi Molecule (TRiMTM) platform. ARO-TSLP is designed to silence the epithelial cytokine thymic stromal lymphopoietin (TSLP), a genetically and clinically validated therapeutic target that activates multiple immune cell lineages to promote asthmatic inflammation. ARO-IAV is designed to silence expression of highly conserved influenza A viruses, including the highly pathogenic avian influenza virus (H5N1).
Details about the ATS presentations are listed below.
American Thoracic Society (ATS) 2024 International Conference – May 17-22, 2024
Title: A First-in-Human Study of ARO-RAGE, a Novel Inhaled RNA-Interference Therapy for Asthma
Date/Time: May 19, 2024, 11:30 a.m. PDT
Type: Late-Breaking Poster
Title: A lung-targeted therapeutic siRNA against highly conserved viral M1 mRNAs effectively limits highly pathogenic influenza A infection in mice
Date/Time: May 20, 2024, 11:30 a.m. PDT
Type: Poster
Title: Lung-targeted RNAi molecules silence human TSLP expression in PCLS cultures and humanized mice and suppress pulmonary allergic inflammation
Date/Time: May 20, 2024, 11:30 a.m. PDT
Type: Poster
Presentation materials may be accessed on the Events and Presentations page in the Investors section of the Arrowhead website.
About Pulmonary TRiMTM Platform
Arrowhead’s pulmonary Targeted RNAi Molecule (TRiMTM) delivery platform facilitates selective delivery of therapeutic small interfering RNAs (siRNAs) to the lung epithelium via an integrin αvβ6 targeting moiety, mediating durable gene silencing upon inhalation utilizing a nebulizer.
About ARO-RAGE
ARO-RAGE is an investigational RNAi therapeutic targeting the receptor for advanced glycation end-products (RAGE) as a potential treatment for inflammatory lung diseases. RAGE is implicated as an upstream mediator of Type-2 and non-Type-2 inflammatory cascades and is involved in the pathogenesis of asthma and numerous inflammatory diseases1,2,3. Silencing RAGE expression via RNAi is designed to reduce the amount of RAGE protein expressed on pulmonary epithelial cells. Reduced RAGE expression in the pulmonary epithelium may result in reduction of RAGE-dependent inflammatory pathways, leading to decreased exacerbation frequency and improved airflow in patients with asthma.
About the ARORAGE-1001 Phase 1/2 Study
ARORAGE-1001 (NCT05276570) is an ongoing Phase 1/2a, randomized, double-blinded, placebo-controlled study in normal healthy volunteers (NHV) (Part 1), in patients with mild to moderate asthma (Part 2), and in patients with high baseline fractional exhaled nitric oxide (FeNO) (Part 3). Subjects receive ascending doses of ARO-RAGE or placebo via nebulizer on Day 1 in the single-ascending dose cohorts or Days 1 and 29 in the multiple-ascending dose cohorts. The objectives of the study include the assessment of safety and tolerability, pharmacokinetics, and pharmacodynamics of ARO-RAGE in NHVs and patients with asthma.
About Arrowhead Pharmaceuticals
Arrowhead Pharmaceuticals develops medicines that treat intractable diseases by silencing the genes that cause them. Using a broad portfolio of RNA chemistries and efficient modes of delivery, Arrowhead therapies trigger the RNA interference mechanism to induce rapid, deep, and durable knockdown of target genes. RNA interference, or RNAi, is a mechanism present in living cells that inhibits the expression of a specific gene, thereby affecting the production of a specific protein. Arrowhead’s RNAi-based therapeutics leverage this natural pathway of gene silencing.
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Source: Arrowhead Pharmaceuticals, Inc.
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Perkins TN. Allergy 2021;76:1350-66. |
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Oczypok EA. JACI 2015;136:747-56. |
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Arrowhead Pharmaceuticals, Inc.
Vince Anzalone, CFA
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ir@arrowheadpharma.com
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Source: Arrowhead Pharmaceuticals, Inc.
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