Ionis announces positive detailed results from the HALOS Study of ION582 in people with Angelman syndrome
Ionis Pharmaceuticals (Nasdaq: IONS) announced positive results from the Phase 1/2 HALOS study of ION582 in people with Angelman syndrome (AS). The study showed consistent clinical improvement in communication, cognition, and motor function. Key findings include:
- 97% of patients in medium and high dose groups showed improvement in overall AS symptoms
- Improvements exceeded those observed in natural history studies
- ION582 demonstrated favorable safety and tolerability at all dose levels
Ionis plans to initiate Phase 3 development in H1 2025. The company views ION582 as a potential cornerstone of its next wave of transformational medicines for neurological conditions.
Ionis Pharmaceuticals (Nasdaq: IONS) ha annunciato risultati positivi dallo studio di Fase 1/2 HALOS su ION582 in persone affette da syndrome di Angelman (AS). Lo studio ha mostrato un miglioramento clinico costante in comunicazione, cognizione e funzione motoria. I principali risultati includono:
- Il 97% dei pazienti nei gruppi a dose media e alta ha mostrato miglioramenti nei sintomi complessivi dell'AS
- I miglioramenti hanno superato quelli osservati negli studi sulla storia naturale
- ION582 ha dimostrato un profilo di sicurezza e tollerabilità favorevole a tutti i livelli di dose
Ionis prevede di avviare lo sviluppo della Fase 3 nella prima metà del 2025. L'azienda considera ION582 come un potenziale pilastro della sua prossima generazione di medicinali trasformativi per condizioni neurologiche.
Ionis Pharmaceuticals (Nasdaq: IONS) anunció resultados positivos del estudio de Fase 1/2 HALOS de ION582 en personas con sindrome de Angelman (AS). El estudio mostró una mejora clínica consistente en comunicación, cognición y función motora. Los hallazgos clave incluyen:
- El 97% de los pacientes en los grupos de dosis media y alta mostraron mejorías en los síntomas generales de AS
- Las mejoras superaron las observadas en estudios de historia natural
- ION582 demostró un perfil de seguridad y tolerabilidad favorable en todos los niveles de dosis
Ionis planea iniciar el desarrollo de Fase 3 en la primera mitad de 2025. La compañía considera a ION582 como una posible piedra angular de su próxima ola de medicamentos transformadores para condiciones neurológicas.
아이오니스 제약(Ionis Pharmaceuticals, Nasdaq: IONS)은 앤젤만 증후군(Angelman syndrome, AS) 환자를 대상으로 한 ION582의 1/2상 HALOS 연구에서 긍정적인 결과를 발표했습니다. 이 연구는 의사소통, 인지 및 운동 기능에서 일관된 임상 개선을 보여주었습니다. 주요 발견 사항은 다음과 같습니다:
- 중간 및 고용량 그룹의 97%의 환자가 전체 AS 증상의 개선을 보였습니다.
- 개선 정도는 자연사 연구에서 관찰된 것보다 뛰어났습니다.
- ION582는 모든 용량 수준에서 유리한 안전성과 내약성을 나타냈습니다.
아이오니스는 2025년 상반기 3상 개발을 시작할 계획입니다. 이 회사는 ION582를 신경학적 상태에 대한 다음 세대 변혁적 약물의 초석으로 간주하고 있습니다.
Ionis Pharmaceuticals (Nasdaq: IONS) a annoncé des résultats positifs de l'étude de Phase 1/2 HALOS sur ION582 chez des personnes atteintes du syndrome d'Angelman (AS). L'étude a montré une amélioration clinique cohérente en communication, cognition et fonction motrice. Les principales conclusions comprennent :
- 97 % des patients des groupes à dose moyenne et élevée ont montré une amélioration des symptômes globaux de l'AS
- Les améliorations ont dépassé celles observées dans les études d'histoire naturelle
- ION582 a démontré un profil de sécurité et de tolérabilité favorable à tous les niveaux de dose
Ionis prévoit de commencer le développement de Phase 3 au premier semestre 2025. L'entreprise considère ION582 comme une pierre angulaire potentielle de sa prochaine vague de médicaments transformateurs pour les conditions neurologiques.
Ionis Pharmaceuticals (Nasdaq: IONS) hat positive Ergebnisse der Phase 1/2 HALOS-Studie zu ION582 bei Personen mit Angelman-Syndrom (AS) bekannt gegeben. Die Studie zeigte eine konsistente klinische Verbesserung in Kommunikation, Kognition und Motorik. Wichtige Ergebnisse umfassen:
- 97% der Patienten in den Gruppen mit mittlerer und hoher Dosis zeigten eine Verbesserung der allgemeinen AS-Symptome
- Die Verbesserungen übertrafen die in naturhistorischen Studien beobachteten
- ION582 zeigte ein günstiges Sicherheits- und Verträglichkeitsprofil auf allen Dosen
Ionis plant, in der ersten Hälfte von 2025 mit der Phase 3-Entwicklung zu beginnen. Das Unternehmen sieht ION582 als potenzielle Grundlage seiner nächsten Generation von transformierenden Medikamenten für neurologische Erkrankungen.
- 97% of patients in medium and high dose groups showed improvement in overall Angelman syndrome symptoms
- ION582 demonstrated favorable safety and tolerability at all dose levels
- Improvements in communication, cognition, and motor function exceeded those observed in natural history studies
- Consistent benefits observed across all ages and genotypes
- Phase 3 development planned for H1 2025
- None.
Insights
Ionis Pharmaceuticals' recent announcement regarding the positive results from the HALOS study of ION582 in Angelman syndrome patients is highly significant. The study shows remarkable improvements in communication, cognition and motor function, with 97% of patients in the medium and high dose groups showing overall symptom improvement. This is especially noteworthy given the lack of effective treatments for Angelman syndrome. The planned Phase 3 development in 2025 suggests a potential breakthrough therapy on the horizon. What stands out is the consistent efficacy observed across different age groups and genotypes, indicating broad applicability. For stakeholders, this could translate into a substantial market opportunity if Phase 3 results are equally promising. However, investors should be mindful of the typical risks associated with clinical trials, including regulatory hurdles and the variability of patient responses in larger populations.
The results from Ionis Pharmaceuticals' HALOS study are likely to have a positive impact on the company's stock. The detailed data showing strong efficacy and favorable safety profile in a challenging indication like Angelman syndrome could drive investor confidence. Initiating Phase 3 development is a critical milestone that often leads to increased market valuation and interest from larger pharmaceutical partners. Furthermore, if ION582 receives eventual approval, it could open a lucrative market given the high unmet need for effective Angelman syndrome therapies. However, the company's financial health will need to be monitored closely as they progress through these expensive and resource-intensive clinical trials. Investors should also consider the competitive landscape and any emerging therapies that might impact ION582's market potential.
From a market research perspective, the HALOS study results position Ionis Pharmaceuticals as a frontrunner in developing treatments for Angelman syndrome. The robustness of data across various functional domains suggests a differentiated product profile, which can be a significant competitive advantage. The high rates of improvement in key areas like communication and motor function, exceeding those reported in natural history studies, underscore the potential of ION582 to address substantial unmet needs in this patient population. As Ionis prepares for Phase 3 trials, they will need to navigate regulatory requirements meticulously to maintain this momentum. The market potential for an approved therapy in Angelman syndrome is considerable, given the current lack of effective treatments and the lifelong nature of the disorder. Despite the promising outlook, it's important to proceed with cautious optimism as Phase 3 trials will be the ultimate test of ION582's efficacy and safety on a larger scale.
- ION582 showed robust and consistent benefit in communication, cognition and motor function in a broad patient population evaluated with a comprehensive set of assessment tools that collect input from parents and clinicians
97% of patients in the medium and high dose groups saw improvement in overall Angelman syndrome symptoms as measured by the SAS-CGI-C- Improvements on the Bayley-4 in cognition, communication and motor function exceeded those observed in natural history studies
- Ionis plans to initiate Phase 3 development in H1 2025
- Ionis to host webcast on Monday, July 22 at 8:00am ET
"Ionis looks forward to collaborating with investigators, regulators and members of the Angelman syndrome community to initiate Phase 3 development for ION582 in the first half of 2025," said Brett Monia, Ph.D., chief executive officer of Ionis. "Ionis has pioneered the discovery and development of groundbreaking medicines for serious neurological conditions including spinal muscular atrophy and amyotrophic lateral sclerosis. These encouraging results from the HALOS study position ION582 to be the cornerstone of Ionis' next wave of transformational, wholly owned medicines for neurological conditions, which currently includes five clinical-stage programs."
AS is a serious, rare neurodevelopmental disorder that is caused by a loss of function in the maternal UBE3A gene. It affects an estimated 1 in 21,000 people worldwide and presents in early childhood as profound and severe developmental delays in motor, language and cognitive functioning, seizures and ataxia. ION582 is an investigational antisense medicine designed to unsilence the normal paternal UBE3A gene to increase production of the UBE3A protein in the brain.
"Angelman syndrome is a serious neurodevelopmental disorder with life-long impairments and dependence on caregivers, for which we currently have only supportive care," said Lynne Bird, M.D., professor of clinical pediatrics at UC San Diego and HALOS study investigator. "We are very encouraged by these promising data with ION582, showing consistent improvements over what we observe in the natural course of the disease."
HALOS Study Results
HALOS included 51 people with AS, and allowed participants aged two-50 to enroll. Results presented today are from the final timepoint of the completed MAD portion of the study at six months. These results include:
- ION582 showed favorable safety and tolerability at all dose levels.
- Evidence of consistent benefit observed across all ages and genotypes as well as clinical improvement observed across key functional areas:
- Improvements in communication, cognition and motor function exceeding the Angelman Syndrome Natural History Study (NHS) were observed on the Bayley-4, an objective and direct clinician-administered assessment of clinical functioning. See details in Table 1 below.
- Clinical improvements were observed across key functional areas in the Vineland-3 and Observer-Reported Communication Ability (ORCA), which are both parent-reported assessment tools.
97% of participants showed clinically meaningful overall improvement on the SAS-CGI-C, which evaluates clinicians' impressions of AS symptoms in study participants.
Table 1: Majority of Participants Demonstrated Benefit in Nearly all Domains Assessed in the HALOS Study1
The percent of participants who improved across the four AS tools evaluated in HALOS is noted below. These results exceed the improvements seen in the NHS, where available, in which people with AS show profound developmental delay from birth through adulthood with function remaining stable with essentially no improvement after ~4 years of age.
Bayley-42,3 | Vineland-32,4 | ORCA2,5-8 | SAS-CGI-C9-12 | |
Cognition | 67 % | — | — | 85 % |
Receptive Communication | 67 % | 89 % | 60 % | — |
Expressive Communication | 69 % | 84 % | 69 % | |
Gross Motor | 46 % | 53 % | — | 74 % |
Fine Motor | 72 % | 63 % | — | 64 % |
Daily Living Skills | * | 74 | — | 62 % |
Socialization | * | 63 | — | — |
Sleep | — | — | — | 61 % |
Behavior | * | * | — | 56 % |
* Analyzed with alternate assessment tool(s) |
1. Medium and high dose groups at 6 months. 2. Improvement exceeds Natural History. 3. Bayley N. Aylward GP. Bayley Scales of Infant and Toddler Development-Fourth Edition. NCS Pearson. (2019). 4. Sparrow S, et. Al. Vineland Adaptive Behavior Scales-Third Edition (Vineland-3). NCS Pearson. (2016). 5. Improvement on ORCA exceeding proposed minimal clinically meaningful difference of ≥2. 6. Zigler CK, et al. Am J Intellect Dev Disabil. (2023). 7. Duke University. Observer-Reported Communication Ability (ORCA) measure scoring manual. Pattern Health. (2023). 8. ORCA T-score range: 25.8–83.8, (standardized, mean=50, SD=10). 9. Improvement on SAS-CGI-C exceeding proposed minimal clinically meaningful difference of ≥1 point. 10. Connor-Ahmad, S. et al. Orphanet J. Rare Dis. (2023). 11. Adapted from Standard CGI-C. 12. SAS-CGI-C response range: Very Much Worse-Very Much Improved. 13. Range across 3 subdomains (personal, community and domestic). 14. Range across 3 subdomains (Coping skills, interpersonal relationships and play and leisure) |
Ionis plans to meet with regulators to review and confirm their Phase 3 study design later this year, which puts the company on track for a pivotal study initiation in H1 2025.
Webcast
Ionis will hold a webcast today at 8:00am ET to discuss this update. Interested parties may access the webcast here. A webcast replay will be available for a limited time.
About the HALOS Study
The global, open-label, multiple-ascending dose (MAD) Phase 1-2a study (NCT05127226) includes 51 patients with Angelman syndrome (AS) aged two – 50 across 11 sites in six countries. Part 1 of the HALOS trial was a three-month, MAD study which evaluated three doses of ION582, with final assessments at six months. All eligible patients transitioned into the Part 2 long-term extension (LTE) portion of the study, which is evaluating the two higher doses of ION582 for an additional 12 months. Part 3 of the study will evaluate eligible patients for up to an additional four years. The primary endpoint is safety and tolerability of multiple doses of ION582 administered by intrathecal administration. Key exploratory measures include change in measures of clinical function: communication, cognition, motor function, sleep, seizures and daily living skills.
About ION582
ION582 is an investigational antisense medicine designed to inhibit the expression of the UBE3A antisense transcript (UBE3A-ATS) and increase production of UBE3A protein, for the potential treatment of Angelman syndrome (AS). In 2022, the
About Angelman Syndrome (AS)
AS is a rare, genetic neurological disease caused by the loss of function of the maternally inherited UBE3A gene. AS typically presents in infancy and is characterized by profound intellectual disability, balance issues, motor impairment, and debilitating seizures. Most patients are unable to speak. Individuals with AS have a normal lifespan but require complete care from a caregiver. Some symptoms can be managed with existing medicines; however, there are no approved disease modifying therapies.
About Ionis' Neurology Franchise
Ionis has been at the forefront of discovering and developing leading neurological disease medicines, including SPINRAZA® (nusinersen), the first approved treatment for spinal muscular atrophy, WAINUATM (eplontersen), a medicine to treat hereditary transthyretin-mediated amyloid polyneuropathy (ATTRv-PN), and QALSODY® (tofersen) for SOD1-ALS. The clinical-stage portfolio includes 11 therapies, of which five are wholly owned by Ionis. Ionis' investigational portfolio includes medicines for which there are few or no disease modifying treatments, such as rare diseases including amyotrophic lateral sclerosis (ALS) and Alexander disease and more common conditions such as Alzheimer's and Parkinson's disease.
About Ionis Pharmaceuticals, Inc.
For three decades, Ionis has invented medicines that bring better futures to people with serious diseases. Ionis currently has five marketed medicines and a leading pipeline in neurology, cardiology, and other areas of high patient need. As the pioneer in RNA-targeted medicines, Ionis continues to drive innovation in RNA therapies in addition to advancing new approaches in gene editing. A deep understanding of disease biology and industry-leading technology propels our work, coupled with a passion and urgency to deliver life-changing advances for patients.
To learn more about Ionis, visit Ionis.com and follow us on X (Twitter) and LinkedIn.
Ionis Forward-looking Statements
This press release includes forward-looking statements regarding Ionis' business, and the therapeutic and commercial potential of Ionis' commercial medicines, ION582, additional medicines in development and technologies. Any statement describing Ionis' goals, expectations, financial or other projections, intentions, or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, including but not limited to those related to our commercial products and the medicines in our pipeline, and particularly those inherent in the process of discovering, developing and commercializing medicines that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such medicines. Ionis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Ionis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Ionis. Except as required by law, we undertake no obligation to update any forward-looking statements for any reason. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis' programs are described in additional detail in Ionis' annual report on Form 10-K for the year ended Dec. 31, 2023, and most recent Form 10-Q, which are on file with the SEC. Copies of these and other documents are available at www.Ionis.com.
In this press release, unless the context requires otherwise, "Ionis," "Company," "we," "our" and "us" all refer to Ionis Pharmaceuticals and its subsidiaries.
Ionis Pharmaceuticals® is a registered trademark of Ionis Pharmaceuticals, Inc.
Ionis Pharmaceuticals Investor Contact: D. Wade Walke, Ph.D. - IR@ionis.com - 760-603-2331
Ionis Pharmaceuticals Media Contact: Hayley Soffer - Media@ionis.com - 760-603-4679
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FAQ
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