Novel Combination of Pozelimab and Cemdisiran (Poze-Cemdi) Achieved Greater Control of Intravascular Hemolysis in Patients with Paroxysmal Nocturnal Hemoglobinuria Compared to Ravulizumab
Regeneron Pharmaceuticals announced positive Phase 3 data for their novel combination treatment pozelimab and cemdisiran (poze-cemdi) in treating paroxysmal nocturnal hemoglobinuria (PNH). The exploratory cohort of the ACCESS-1 trial showed superior results compared to standard-of-care ravulizumab.
Key findings showed that 96% of patients achieved adequate LDH control with poze-cemdi, compared to 80% with ravulizumab. Additionally, 93% achieved LDH normalization with poze-cemdi versus 65% with ravulizumab. The treatment demonstrated an 84% decrease in LDH from baseline at week 26.
The safety profile was comparable to approved C5 inhibitors, with treatment-emergent adverse events occurring in 84% of poze-cemdi patients versus 87% for ravulizumab. The combination therapy offers the advantage of four-week subcutaneous delivery with potential for self-administration.
Regeneron Pharmaceuticals ha annunciato dati positivi della fase 3 per il loro nuovo trattamento combinato pozelimab e cemdisiran (poze-cemdi) nel trattamento dell'emoglobinuria notturna parossistica (PNH). Il gruppo esplorativo dello studio ACCESS-1 ha mostrato risultati superiori rispetto al trattamento standard ravulizumab.
Tra i risultati chiave, si è osservato che il 96% dei pazienti ha raggiunto un controllo adeguato della LDH con poze-cemdi, rispetto all'80% con ravulizumab. Inoltre, il 93% ha ottenuto la normalizzazione della LDH con poze-cemdi contro il 65% con ravulizumab. Il trattamento ha dimostrato una riduzione dell'84% della LDH rispetto al valore iniziale alla settimana 26.
Il profilo di sicurezza era comparabile a quello degli inibitori C5 approvati, con eventi avversi emergenti dal trattamento che si sono verificati nell'84% dei pazienti trattati con poze-cemdi contro l'87% per ravulizumab. La terapia combinata offre il vantaggio di una somministrazione sottocutanea ogni quattro settimane con la possibilità di auto-somministrazione.
Regeneron Pharmaceuticals anunció datos positivos de la fase 3 para su nuevo tratamiento combinado pozelimab y cemdisiran (poze-cemdi) en el tratamiento de la hemoglobinuria nocturna paroxística (PNH). La cohorte exploratoria del ensayo ACCESS-1 mostró resultados superiores en comparación con el tratamiento estándar ravulizumab.
Los hallazgos clave mostraron que el 96% de los pacientes logró un control adecuado de LDH con poze-cemdi, en comparación con el 80% con ravulizumab. Además, el 93% alcanzó la normalización de LDH con poze-cemdi frente al 65% con ravulizumab. El tratamiento demostró una reducción del 84% en LDH desde la línea base en la semana 26.
El perfil de seguridad fue comparable al de los inhibidores de C5 aprobados, con eventos adversos emergentes del tratamiento que ocurrieron en el 84% de los pacientes tratados con poze-cemdi frente al 87% para ravulizumab. La terapia combinada ofrece la ventaja de una administración subcutánea de cuatro semanas con potencial para auto-administración.
레겐론 제약이 새 조합 치료제 포젤리맙과 세므디시란(포제-세mdi)의 임상 3상 긍정적인 데이터를 발표했습니다. ACCESS-1 시험의 탐색군은 표준 치료인 라불리주맙에 비해 우수한 결과를 보였습니다.
주요 발견에 따르면, 96%의 환자가 포제-세mdi로 LDH 조절이 적절하게 이루어졌고, 라불리주맙의 경우는 80%였습니다. 또한, 93%는 LDH 정상화를 달성했습니다 포제-세mdi로, 라불리주맙은 65%였습니다. 치료는 26주 차에 기준선 대비 LDH가 84% 감소하는 것으로 나타났습니다.
안전성 프로필은 승인된 C5 억제제와 유사했으며, 치료에서 병발된 이상 반응은 포제-세mdi 환자의 84%에서 발생했으며, 라불리주맙은 87%였습니다. 이 조합 치료는 4주 간의 피하 투여와 자가 투여 가능성의 장점을 제공합니다.
Regeneron Pharmaceuticals a annoncé des données positives de phase 3 pour leur nouveau traitement combiné pozelimab et cemdisiran (poze-cemdi) dans le traitement de l'hémoglobinurie nocturne paroxystique (PNH). La cohorte exploratoire de l'essai ACCESS-1 a montré des résultats supérieurs par rapport au traitement standard ravulizumab.
Les principales découvertes ont montré que 96 % des patients ont atteint un contrôle adéquat de la LDH avec poze-cemdi, contre 80 % avec ravulizumab. De plus, 93 % ont réussi à normaliser la LDH avec poze-cemdi contre 65 % avec ravulizumab. Le traitement a montré une réduction de 84 % de la LDH par rapport à la ligne de base à la semaine 26.
Le profil de sécurité était comparable à celui des inhibiteurs de C5 approuvés, avec des événements indésirables émergents du traitement survenant chez 84 % des patients traités avec poze-cemdi contre 87 % pour ravulizumab. La thérapie combinée offre l'avantage d'une administration sous-cutanée toutes les quatre semaines avec un potentiel d'auto-administration.
Regeneron Pharmaceuticals kündigte positive Daten der Phase 3 für ihre neuartige Kombinationstherapie pozelimab und cemdisiran (poze-cemdi) zur Behandlung der paroxysmalen nächtlichen Hämoglobinurie (PNH) an. Die explorative Kohorte der ACCESS-1-Studie wies überlegene Ergebnisse im Vergleich zur Standardbehandlung ravulizumab auf.
Wichtige Ergebnisse zeigten, dass 96% der Patienten eine adäquate Kontrolle der LDH mit poze-cemdi erreichten, verglichen mit 80% bei ravulizumab. Darüber hinaus erreichten 93% eine Normalisierung der LDH mit poze-cemdi im Vergleich zu 65% bei ravulizumab. Die Behandlung zeigte eine Senkung der LDH um 84% gegenüber dem Ausgangswert in Woche 26.
Das Sicherheitsprofil war vergleichbar mit den zugelassenen C5-Inhibitoren, wobei behandlungsbedingte unerwünschte Ereignisse bei 84% der poze-cemdi Patienten im Vergleich zu 87% bei ravulizumab auftraten. Die Kombinationstherapie bietet den Vorteil einer vierwöchigen subkutanen Verabreichung mit der Möglichkeit zur Selbstverabreichung.
- 96% of patients achieved adequate LDH control with poze-cemdi vs 80% with ravulizumab
- 93% achieved LDH normalization with poze-cemdi vs 65% with ravulizumab
- 84% decrease in LDH from baseline at week 26 with poze-cemdi vs 74% with ravulizumab
- 4 out of 5 patients who failed ravulizumab treatment achieved LDH control after switching to poze-cemdi
- Potential for self-administration through subcutaneous delivery
- Two serious adverse events occurred in patients receiving poze-cemdi
- One fatal case of sepsis and disseminated intravascular coagulation reported
Insights
The Phase 3 trial results for poze-cemdi demonstrate compelling clinical superiority over the current standard-of-care ravulizumab in PNH treatment. The combination therapy achieved 96% LDH control rate versus 80% for ravulizumab, with notably better maintenance of complement inhibition throughout the dosing period. The ability to normalize LDH levels in 93% of patients (versus 65% for ravulizumab) suggests significantly better disease control.
The subcutaneous administration route every 4 weeks offers a meaningful advantage over current IV-based treatments, potentially improving treatment adherence and patient quality of life. The safety profile appears comparable to existing C5 inhibitors, with no concerning new safety signals. Most notably, 4 out of 5 previous ravulizumab non-responders achieved LDH control after switching to poze-cemdi, indicating its potential as a superior therapeutic option for difficult-to-treat cases.
This data represents a significant market opportunity for Regeneron in the PNH space, currently dominated by AstraZeneca's Ultomiris (ravulizumab). The superior efficacy profile, coupled with a more convenient administration route, positions poze-cemdi to potentially capture substantial market share. The global PNH therapeutics market, valued at approximately
The demonstrated ability to treat ravulizumab non-responders is particularly valuable, as it addresses an unmet medical need and could lead to preferred positioning in treatment algorithms. The combination's dual mechanism of action represents a first-in-class approach that could extend beyond PNH to other complement-mediated diseases, significantly expanding the potential market opportunity.
Head-to-head exploratory cohort of a Phase 3 trial showed first-in-class poze-cemdi combination treatment helped patients achieve and maintain greater disease control, as measured by lactate dehydrogenase (LDH) levels, compared to standard-of-care ravulizumab
Five patients receiving ravulizumab did not achieve meaningful LDH control compared to one patient receiving poze-cemdi; after switching to the combination, four of the five previously treated with ravulizumab achieved LDH control
A separate registrational cohort is ongoing, investigating poze-cemdi against eculizumab
TARRYTOWN, N.Y., Dec. 07, 2024 (GLOBE NEWSWIRE) -- Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced positive updated Phase 3 data of an exploratory cohort from the ACCESS-1 trial investigating its first-in-class pozelimab and cemdisiran (poze-cemdi) combination treatment against ravulizumab, a standard-of-care complement factor 5 (C5) inhibitor, in patients with paroxysmal nocturnal hemoglobinuria (PNH). Results were shared during an oral session at the American Society of Hematology (ASH) 2024 Annual Meeting and support continued development of poze-cemdi in PNH, including in a separate registrational cohort, as well as in other complement-mediated diseases. Poze-Cemdi is a first-in-class combination of an antibody and an siRNA targeting C5: pozelimab is a fully human monoclonal antibody designed to block the activity of C5, while cemdisiran is an investigational siRNA therapeutic that reduces circulating levels of C5.
PNH is an ultra-rare, chronic, life-threatening complement-mediated blood disorder. People with PNH have an acquired genetic mutation in which red blood cells are destroyed (known as hemolysis) by the complement system, which is part of the innate immune system. The lysed red blood cells release lactate dehydrogenase (LDH), which is a biomarker used to measure the degree of hemolysis. Hemolysis causes a range of symptoms including fatigue, shortness of breath, and life-threatening blood clots. Inhibition of C5, a protein involved in complement system activation, is an established treatment approach to prevent intravascular hemolysis, which occurs inside blood vessels; LDH can be used to determine the effectiveness of C5 inhibition. Addressing intravascular hemolysis is a critical treatment approach to reducing the symptoms and risk of life-threatening complications of PNH.
“C5 inhibitors are widely considered the mainstay of PNH treatment, but a proportion of patients still do not achieve adequate control of intravascular hemolysis, may experience residual anemia, and may feel significant treatment burden, as many of these therapies require clinic or home visits for intravenous delivery,” said Christopher Patriquin, M.D., MSc, Assistant Professor of Medicine, Hematology, at the University of Toronto, hematologist at University Health Network and a trial investigator. “In this Phase 3 exploratory cohort, the complementary mechanisms of pozelimab and cemdisiran enabled complete, rapid, uninterrupted and durable inhibition of terminal complement throughout the dosing interval. The combination helped more patients achieve target LDH levels compared to the current standard-of-care C5 inhibitor, with the added benefit of infrequent four-week subcutaneous delivery that has potential for self-administration. These data validate this novel combination approach, and we look forward to results from the registrational cohort, which if repeated, could help transform what may be possible for many people with PNH.”
Updated results from an exploratory arm (Cohort A) of the ACCESS-1 trial, as well as interim results from a follow-on, open label extension (OLE) were presented at ASH. Patients were naïve to complement inhibition, with the primary endpoint of Cohort A being percent change in LDH at 26 weeks. LDH is a well-accepted biomarker of intravascular hemolysis that measures how effective a treatment is at inhibiting the destruction of red blood cells and has also demonstrated a correlation to clinical outcomes.1 Adequate control of hemolysis is defined as LDH levels of ≤1.5 times upper limit of normal (ULN), while normalization is defined as ≤1 times ULN, respectively.
In Cohort A, patients were randomized to receive either poze-cemdi or ravulizumab. The ravulizumab arm generally responded as would be expected based on historical clinical trial data, which indicate that
96% achieved adequate LDH control (≤1.5 x ULN) across study visits (weeks 8-26) on average with poze-cemdi, compared to80% with ravulizumab. At 26 weeks, 5 patients receiving ravulizumab, compared with 1 patient receiving poze-cemdi, did not achieve meaningful LDH control.93% achieved LDH normalization (≤1 x ULN) across study visits (week 8-26) on average with poze-cemdi, compared to65% with ravulizumab.84% decrease in LDH from baseline at week 26 with poze-cemdi compared to74% with ravulizumab.- The CH50 profile observed with poze-cemdi demonstrated complete and uninterrupted inhibition of terminal complement, compared to the profile for ravulizumab showing loss of inhibition at the end of the dosing interval.
After week 26, all patients who completed ACCESS-1 could enroll in a follow-on OLE trial and receive poze-cemdi, including those who initially received ravulizumab (n=19). At the start of the OLE,
The safety profile of poze-cemdi was generally consistent with approved C5 inhibitors. During ACCESS-1, treatment-emergent adverse events (TEAEs) occurred in
In the OLE, among patients who switched to poze-cemdi from ravulizumab,
The potential use of pozelimab and cemdisiran for the treatment of PNH is investigational and has not been approved by any regulatory authority.
About the Pozelimab and Cemdisiran Clinical Trial Program
Pozelimab and cemdisiran are being evaluated in separate Phase 3 trials for several complement-mediated disorders, including PNH, myasthenia gravis (MG) and geographic atrophy (GA).
PNH: ACCESS-1 is a randomized, active-controlled study comprised of two cohorts, evaluating poze-cemdi in patients with PNH who are naïve to, or have not recently received, complement inhibitor therapy. The first cohort (Cohort A) is an exploratory cohort examining the combination administered subcutaneously as a maintenance regimen every four weeks compared to ravulizumab delivered as a maintenance regimen every eight weeks by intravenous infusion. Cohort B is a registrational cohort examining poze-cemdi against eculizumab. Patients in both cohorts may participate in a follow-on OLE study (ACCESS-EXTENSION) assessing the long-term safety and efficacy of the combination, including in patients who switch from ravulizumab or eculizumab.
MG: NIMBLE is a randomized, double-blind placebo controlled trial evaluating poze-cemdi as well as cemdisiran monotherapy in patients with generalized MG.
GA: SIENNA is a randomized, double-blind, placebo controlled trial evaluating poze-cemdi as well as cemdisiran monotherapy in patients with GA secondary to age-related macular degeneration.
For more information, visit the Regeneron clinical trials website, or contact clinicaltrials@regeneron.com or +1 844-734-6643.
The pozelimab and cemdisiran combination is being developed under an agreement with Alnylam Pharmaceuticals, Inc.
About Regeneron in Hematology
At Regeneron, we’re applying more than three decades of biology expertise with our proprietary VelociSuite® technologies to develop medicines for patients with diverse blood cancers and rare blood disorders.
Our blood cancer research is focused on bispecific antibodies that are being investigated both as monotherapies and in combination with each other and emerging therapeutic modalities. Together, they provide us with unique combinatorial flexibility to develop customized and potentially synergistic cancer treatments.
Our research and collaborations to develop potential treatments for rare blood disorders include explorations in antibody medicine, gene editing and gene-knockout technologies, and investigational RNA approaches focused on depleting abnormal proteins or blocking disease-causing cellular signaling.
About Regeneron's VelocImmune Technology
Regeneron's VelocImmune technology utilizes a proprietary genetically engineered mouse platform endowed with a genetically humanized immune system to produce optimized fully human antibodies. When Regeneron's co-Founder, President and Chief Scientific Officer George D. Yancopoulos was a graduate student with his mentor Frederick W. Alt in 1985, they were the first to envision making such a genetically humanized mouse, and Regeneron has spent decades inventing and developing VelocImmune and related VelociSuite® technologies. Dr. Yancopoulos and his team have used VelocImmune technology to create a substantial proportion of all original, FDA-approved or authorized fully human monoclonal antibodies. This includes REGEN-COV® (casirivimab and imdevimab), Dupixent® (dupilumab), Libtayo® (cemiplimab-rwlc), Praluent® (alirocumab), Kevzara® (sarilumab), Evkeeza® (evinacumab-dgnb), Inmazeb® (atoltivimab, maftivimab and odesivimab-ebgn) and Veopoz® (pozelimab).
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Regeneron (NASDAQ: REGN) is a leading biotechnology company that invents, develops and commercializes life-transforming medicines for people with serious diseases. Founded and led by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to numerous approved treatments and product candidates in development, most of which were homegrown in our laboratories. Our medicines and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, neurological diseases, hematologic conditions, infectious diseases, and rare diseases.
Regeneron pushes the boundaries of scientific discovery and accelerates drug development using our proprietary technologies, such as VelociSuite®, which produces optimized fully human antibodies and new classes of bispecific antibodies. We are shaping the next frontier of medicine with data-powered insights from the Regeneron Genetics Center® and pioneering genetic medicine platforms, enabling us to identify innovative targets and complementary approaches to potentially treat or cure diseases. For more information, please visit www.Regeneron.com or follow Regeneron on LinkedIn, Instagram, Facebook or X.
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1 Schrezenmeier, H., Kulasekararaj, A., Mitchell, L. et al. Predictors for improvement in patient-reported outcomes: post hoc analysis of a phase 3 randomized, open-label study of eculizumab and ravulizumab in complement inhibitor-naive patients with paroxysmal nocturnal hemoglobinuria. Ann Hematol 103, 5-15 (2024).
2 Ultomiris (ravulizumab) [package insert]. Boston, MA: Alexion Pharmaceuticals, Inc.; 2018.
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