Pulmovant presents positive proof-of-concept data from the Phase 1b ATMOS study of Mosliciguat in Pulmonary Hypertension at European Respiratory Society Congress
Pulmovant, a Roivant company, presented positive proof-of-concept data from the Phase 1b ATMOS study of Mosliciguat in Pulmonary Hypertension at the European Respiratory Society Congress. Mosliciguat, a potential first-in-class, inhaled soluble Guanylate Cyclase (sGC) activator, showed promising results:
- Single dose led to sustained, clinically meaningful mean peak reduction in pulmonary vascular resistance (PVR) of up to 38%
- Once-daily dosing via dry powder inhaler was well tolerated
- Low rates of treatment-emergent adverse events observed
The global Phase 2 'PHocus' study in ~120 patients with PH associated with interstitial lung disease (PH-ILD) is set to begin soon. PH-ILD affects ~200,000 patients in the U.S. and Europe, with treatment options.
Pulmovant, un'azienda di Roivant, ha presentato dati positivi di prova di concetto dallo studio di Fase 1b ATMOS su Mosliciguat per l'Ipertensione Polmonare al Congresso della Società Respiratoria Europea. Mosliciguat, un potenziale attivatore di Guanylate Cyclase (sGC) solubile per inalazione di prima classe, ha mostrato risultati promettenti:
- Un'unica dose ha portato a una riduzione sostenuta e clinicamente significativa della media del picco di resistenza vascolare polmonare (PVR) fino al 38%
- Dosi giornaliere tramite inalatore a polvere secca sono state ben tollerate
- Sono state osservate basse percentuali di eventi avversi emergenti dal trattamento
Lo studio globale di Fase 2 'PHocus' in ~120 pazienti con PH associata a malattia polmonare interstiziale (PH-ILD) inizierà presto. La PH-ILD colpisce ~200.000 pazienti negli Stati Uniti e in Europa, con poche opzioni terapeutiche.
Pulmovant, una empresa de Roivant, presentó datos positivos de prueba de concepto del estudio de Fase 1b ATMOS sobre Mosliciguat en Hipertensión Pulmonar en el Congreso de la Sociedad Europea de Respiración. Mosliciguat, un potencial activador de Guanylate Cyclase (sGC) soluble por inhalación de primera clase, mostró resultados prometedores:
- Una sola dosis llevó a una reducción sostenida y clínicamente significativa de la media del pico de resistencia vascular pulmonar (PVR) de hasta el 38%
- La dosificación diaria a través de un inhalador de polvo seco fue bien tolerada
- Se observaron bajas tasas de eventos adversos emergentes del tratamiento
El estudio global de Fase 2 'PHocus' en ~120 pacientes con PH asociada a enfermedad pulmonar intersticial (PH-ILD) comenzará pronto. La PH-ILD afecta a ~200,000 pacientes en EE. UU. y Europa, con opciones de tratamiento limitadas.
Pulmovant는 Roivant의 회사로서 유럽호흡기학회에서 모슬리시구앗(Mosliciguat)의 폐 고혈압 관련 1b 단계 ATMOS 연구에서 긍정적인 개념 증명 데이터를 발표했습니다. 모슬리시구앗은 첫 번째 클래스의 흡입형 용해성 구아닐레이트 시클라제(sGC) 활성제로서 희망적인 결과를 보였습니다:
- 단일 용량 투여로 폐혈관 저항(PVR) 평균 피크를 최대 38%까지 의미있게 지속적으로 감소시켰습니다.
- 건조 분말 흡입기를 통한 하루 한 번의 투여가 잘 견뎌졌습니다.
- 치료에서 발생한 부작용의 비율이 낮게 관찰되었습니다.
인터스티티셜 폐 질환(PH-ILD)과 관련된 약 120명의 환자에서 진행될 전세계 2상 연구 'PHocus'가 곧 시작될 예정입니다. PH-ILD는 미국과 유럽에서 약 20만명의 환자에게 영향을 미치며, 치료 옵션이 제한적입니다.
Pulmovant, une entreprise de Roivant, a présenté des données positives de preuve de concept de l'étude de phase 1b ATMOS sur Mosliciguat pour l'hypertension pulmonaire lors du Congrès de la Société Européenne de Respiratoire. Mosliciguat, un potentiel activateur de Guanylate Cyclase (sGC) soluble inhalé de première classe, a montré des résultats prometteurs :
- Une dose unique a conduit à une réduction soutenue et cliniquement significative de la moyenne du pic de résistance vasculaire pulmonaire (PVR) allant jusqu'à 38%
- La posologie quotidienne via inhalateur en poudre sèche a été bien tolérée
- Taux d'événements indésirables émergents observés ont été faibles
L'étude mondiale de phase 2 'PHocus' chez ~120 patients atteints de PH associée à une maladie pulmonaire interstitielle (PH-ILD) va bientôt commencer. La PH-ILD touche environ 200 000 patients aux États-Unis et en Europe, avec des options de traitement limitées.
Pulmovant, ein Unternehmen von Roivant, hat positive Proof-of-Concept-Daten aus der Phase 1b ATMOS-Studie von Mosliciguat bei pulmonaler Hypertonie auf dem Kongress der Europäischen Atemwegsgesellschaft vorgestellt. Mosliciguat, ein potenzieller erster inhalativer, löslicher Guanylatecyclase (sGC) Aktivator, zeigte vielversprechende Ergebnisse:
- Eine Einzeldosis führte zu einer nachhaltigen, klinisch signifikanten durchschnittlichen Spitzenreduktion der pulmonalen Gefäßresistenz (PVR) von bis zu 38%
- Die tägliche Dosierung über einen Trockenpulverinhalator wurde gut vertragen
- Es wurden geringe Raten von behandlungsbedingten unerwünschten Ereignissen beobachtet
Die globale Phase-2-Studie 'PHocus' bei ~120 Patienten mit PH, die mit interstitieller Lungenerkrankung (PH-ILD) assoziiert sind, wird bald beginnen. PH-ILD betrifft ~200.000 Patienten in den USA und Europa, mit begrenzten Behandlungsoptionen.
- Mosliciguat showed a mean peak reduction in pulmonary vascular resistance (PVR) of up to 38% in PH patients
- Once-daily dosing via dry powder inhaler was well tolerated with low rates of treatment-emergent adverse events
- Mosliciguat demonstrated a favorable safety profile in 170 participants across its Phase 1 development program
- The drug has a 40-hour half-life, supporting convenient once-daily dosing
- Mosliciguat's unique formulation requires just one inhalation per day, unlike currently approved therapies
- Direct delivery to the lungs minimizes risk of serious adverse effects seen with systemic vasodilators
- The study was non-randomized and open-label, which may introduce bias in the results
- The Phase 1b ATMOS study had a relatively small sample size of 38 patients
- Efficacy and safety in larger populations and long-term use still need to be established in further clinical trials
Insights
The Phase 1b ATMOS study results for mosliciguat in pulmonary hypertension (PH) are highly promising. The 38% peak reduction in pulmonary vascular resistance (PVR) is impressive, potentially setting a new benchmark in PH treatment efficacy. The drug's novel mechanism as an sGC activator, functioning independently of heme and NO, could offer a significant advantage in oxidative environments typical of PH. The favorable safety profile and once-daily dosing via dry powder inhaler further enhance its potential. The upcoming Phase 2 PHocus study focusing on PH-ILD, a condition affecting ~200,000 patients in the U.S. and Europe with treatment options, represents a substantial market opportunity. However, it's important to note that these are early-stage results and further studies are needed to confirm long-term efficacy and safety.
Pulmovant's mosliciguat shows significant potential in the pulmonary hypertension market. The addressable market of ~200,000 PH-ILD patients in the U.S. and Europe presents a substantial commercial opportunity. Given the lack of approved treatments for PH-ILD, successful development could lead to rapid market penetration and potentially high pricing power. The once-daily dosing and dry powder inhaler formulation could provide a competitive edge over existing therapies. However, investors should consider that the drug is still in early stages, with the Phase 2 trial yet to begin. While promising, there's still a long road to potential approval and commercialization. The positive data could potentially increase Roivant's (NASDAQ: ROIV) valuation, but this is contingent on continued successful development and eventual market entry.
As an oncology specialist, I'm intrigued by mosliciguat's potential in treating pulmonary hypertension associated with interstitial lung disease (PH-ILD). Many cancer treatments, particularly radiation therapy to the chest, can lead to ILD as a side effect, which can progress to PH-ILD. The 38% reduction in PVR is impressive and could significantly improve outcomes for these patients. The once-daily dosing via dry powder inhaler could enhance patient compliance, a important factor in managing chronic conditions. Moreover, the drug's mechanism as an sGC activator, independent of heme and NO, could be particularly beneficial in the oxidative environment often seen in post-cancer treatment lung conditions. However, we need to see results from larger, longer-term studies to fully understand its efficacy and safety profile in this specific patient population.
- Mosliciguat is a potential first-in-class, inhaled soluble Guanylate Cyclase (sGC) activator with targeted delivery to the lungs via once-daily administration, which may have broad applicability across the spectrum of pulmonary hypertension (PH)
- In the Phase 1b ATMOS study, presented today at the European Respiratory Society (ERS) Congress, a single dose of inhaled mosliciguat in PH patients (N=38) led to sustained, clinically meaningful mean peak reduction in pulmonary vascular resistance (PVR) of up to
38% , one of the highest reductions seen in PH trials to date - Once-daily dosing via dry powder inhaler (DPI) was well tolerated, with low rates of treatment-emergent adverse events (TEAEs)
- The global Phase 2 “PHocus” study of mosliciguat in ~120 patients with PH associated with interstitial lung disease (PH-ILD) is expected to begin imminently. PH-ILD affects ~200,000 patients in the U.S. and Europe, a prevalence that is meaningfully greater than that of pulmonary arterial hypertension (PAH), with limited to no treatment options
WALTHAM, Mass., Sept. 10, 2024 (GLOBE NEWSWIRE) -- Pulmovant, a Roivant (Nasdaq: ROIV) company, today announced the presentation of data from the proof-of-concept Phase 1b ATMOS1 study during the ERS Congress in Vienna, Austria. ATMOS (NCT03754660) evaluated mosliciguat, a potential first-in-class, inhaled sGC activator with targeted delivery to the lungs and once-daily administration, in PH patients.
Mosliciguat has been extensively characterized across a robust Phase 1 program with 170 participants dosed to date, including patients with PH in the ATMOS study, and based these data has the potential to show differentiated efficacy, safety, and convenience. Mosliciguat’s target, sGC, is a key enzyme in the nitric oxide (NO) / cyclic guanosine monophosphate (cGMP) signaling pathway that catalyzes cGMP production leading to increased vasodilation, reduced inflammation and apoptosis, reverse vascular remodeling, and anti-fibrotic effects. Unlike sGC stimulators, which require reduced heme and NO to exert their effect on sGC, mosliciguat is an sGC activator that works independently of heme and NO. This also allows mosliciguat to potentially retain efficacy in highly oxidative environments typical of PH, where stimulators are expected to lose efficacy given heme is oxidized or removed and NO levels are depleted.
“We believe mosliciguat can transform the lives of patients living with pulmonary hypertension, and I am excited to announce this potential first-in-class and best-in-category therapy. Mosliciguat has the incredibly rare advantage of potential differentiation across three separate key areas - efficacy, safety, and convenience in administration. We are impressed with the data generated so far, particularly the PVR results, and we believe its differentiated mechanism as an sGC activator can have maximal impact on PH-ILD patients, a large population with severe disease, high morbidity and mortality, and few treatment options,” said Matt Gline, Roivant’s Chief Executive Officer.
ATMOS was a non-randomized, open-label, dose escalation, proof-of-concept Phase 1b trial that assessed the efficacy, safety, tolerability, and pharmacokinetics of mosliciguat following single dose inhaled administration in participants aged between 18 and 80 years with World Health Organization (WHO) Group 1 PH (pulmonary arterial hypertension (PAH)) or Group 4 PH (chronic thromboembolic pulmonary hypertension (CTEPH)). Overall, 38 patients received mosliciguat in this study. In the per-protocol set of patients (N=20), mosliciguat 1.0, 2.0 and 4.0 mg doses led to mean peak percentage reductions in PVR from baseline of -
Overall, in its Phase 1 development program in 170 healthy volunteers and PH patients, mosliciguat has shown a favorable safety profile, dose-dependent increases in cGMP, and a 40-hour half-life supporting convenient once-daily dosing. Mosliciguat is unique among inhaled PH therapies, requiring just one inhalation per day – all currently approved therapies require multiple inhalations, multiple times per day. Mosliciguat is formulated for delivery via DPI, providing greater convenience to patients compared to nebulizers required for many existing inhaled PH therapies. Direct delivery to the lungs also minimizes risk of serious adverse effects seen with systemic vasodilators, such as worsening of oxygenation status. In addition to greater efficacy as evidenced by PVR in ATMOS, a generally favorable safety profile and ease of administration support the potential differentiation for mosliciguat.
Pulmovant will advance the clinical program to assess mosliciguat in its global Phase 2 PHocus study in patients with PH-ILD, a subgroup of Group 3 PH. Approximately 120 patients will be enrolled in the study, which will start imminently. An estimated 200,000 patients across the U.S. and Europe are living with PH-ILD and have limited or no approved treatment options. The PH-ILD prevalence is meaningfully greater than that of PAH, representing an attractive commercial opportunity with limited competition and high unmet patient need.
“We have elected to initiate our global Phase 2 PHocus study in PH-ILD because of the lack of treatment options for patients coupled with the impressive Phase 1b results and strong biologic rationale,” noted Drew Fromkin, Pulmovant’s Chief Executive Officer. “PH-ILD is a devastating disease that is associated with high morbidity and mortality as well as poor quality of life. We are committed to making a significant difference for these patients and have assembled a stellar team, alongside our world-class investigators and advisors, to advance and optimize mosliciguat’s development.”
About Pulmonary Hypertension and Interstitial Lung Disease
Pulmonary hypertension (PH) is a progressive and debilitating condition characterized by high blood pressure in the blood vessels of the lungs. This elevated pressure forces the heart to work harder to pump blood through the lungs, leading to symptoms such as shortness of breath, fatigue, chest pain, and dizziness. The WHO has classified PH into five groups based on their underlying causes, symptoms, and treatment approaches. Group 3 PH is a subtype of PH that arises from lung diseases, such as interstitial lung disease (ILD). ILD describes a large group of diseases that cause progressive damage to the lungs, making it difficult for patients to breathe. Up to 200,000 patients across U.S. and Europe are living with PH-ILD, a subset of Group 3 PH, and have limited to no approved treatment options. Click here for more information.
About Pulmovant
Pulmovant is a clinical-stage biotechnology company developing innovative therapies for patients suffering from pulmonary diseases. Pulmovant’s first program, mosliciguat is designed to provide an effective, once-daily, inhaled treatment option for patients with pulmonary hypertension (PH). Mosliciguat is a novel, potential first-in-class, sGC activator with a differentiated mechanism that may have broad applicability across the PH spectrum.
For more information, please visit https://www.pulmovant.com.
© 2024 Pulmovant, Inc. All Rights Reserved. All trademarks are the property of their respective owners.
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1 ATMOS, a Proof-of-Concept trial of inhaled mosliciguat in untreated PAH or CTEPH was presented during poster session (PS) 31, poster number PA5238, at the European Respiratory Society Congress on September 10, 2024, from 12:30 to 2:00 PM CET.
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