Verve Therapeutics Announces Positive Initial Data from the Heart-2 Phase 1b Clinical Trial of VERVE-102, an In Vivo Base Editing Medicine Targeting PCSK9
Verve Therapeutics has announced positive initial data from the Heart-2 Phase 1b clinical trial of VERVE-102, a single-dose base editing treatment targeting PCSK9 for cardiovascular disease. The trial included 14 participants with heterozygous familial hypercholesterolemia (HeFH) and/or premature coronary artery disease (CAD).
Key findings across three dose cohorts (0.3, 0.45, and 0.6 mg/kg) showed:
- Mean LDL-C reduction of 53% and maximum reduction of 69% in the 0.6 mg/kg cohort
- Dose-dependent decreases in blood PCSK9 protein levels
- No treatment-related serious adverse events
- No clinically significant changes in ALT or platelets
The company plans to announce final dose escalation data in H2 2025, initiate Phase 2 trials, and receive Eli Lilly's decision on their PCSK9 program opt-in. Current funding is expected to last until mid-2027.
Verve Therapeutics ha annunciato dati iniziali positivi dal trial clinico Heart-2 di fase 1b per VERVE-102, un trattamento di editing genetico in un'unica dose mirato al PCSK9 per le malattie cardiovascolari. Lo studio ha incluso 14 partecipanti con ipercolesterolemia familiare eterozigote (HeFH) e/o malattia coronarica prematura (CAD).
I risultati chiave tra tre coorti di dosaggio (0.3, 0.45 e 0.6 mg/kg) hanno mostrato:
- Una riduzione media del LDL-C del 53% e una riduzione massima del 69% nella coorte da 0.6 mg/kg
- Riduzioni dipendenti dalla dose nei livelli di proteina PCSK9 nel sangue
- Nessun evento avverso grave correlato al trattamento
- Nessun cambiamento clinicamente significativo in ALT o piastrine
L'azienda prevede di annunciare i dati finali sull'escalation della dose nel secondo semestre del 2025, avviare studi di fase 2 e ricevere la decisione di Eli Lilly sul loro programma di opt-in per il PCSK9. Il finanziamento attuale è previsto durare fino a metà del 2027.
Verve Therapeutics ha anunciado datos iniciales positivos del ensayo clínico Heart-2 de fase 1b de VERVE-102, un tratamiento de edición genética de una sola dosis dirigido a PCSK9 para enfermedades cardiovasculares. El ensayo incluyó a 14 participantes con hipercolesterolemia familiar heterocigota (HeFH) y/o enfermedad coronaria prematura (CAD).
Los hallazgos clave en tres cohortes de dosis (0.3, 0.45 y 0.6 mg/kg) mostraron:
- Una reducción media del LDL-C del 53% y una reducción máxima del 69% en la cohorte de 0.6 mg/kg
- Disminuciones dependientes de la dosis en los niveles de proteína PCSK9 en sangre
- Ningún evento adverso grave relacionado con el tratamiento
- Ningún cambio clínicamente significativo en ALT o plaquetas
La empresa planea anunciar los datos finales de escalación de dosis en el segundo semestre de 2025, iniciar ensayos de fase 2 y recibir la decisión de Eli Lilly sobre su programa de opt-in para PCSK9. Se espera que la financiación actual dure hasta mediados de 2027.
Verve Therapeutics는 심혈관 질환을 위한 PCSK9을 목표로 하는 단일 용량 기초 편집 치료제인 VERVE-102의 Heart-2 1b 임상 시험에서 긍정적인 초기 데이터를 발표했습니다. 이 시험에는 이형접합 가족성 고콜레스테롤혈증(HeFH) 및/또는 조기 관상 동맥 질환(CAD)을 가진 14명의 참가자가 포함되었습니다.
세 가지 용량 그룹(0.3, 0.45 및 0.6 mg/kg)에서의 주요 결과는 다음과 같습니다:
- 0.6 mg/kg 그룹에서 평균 LDL-C가 53% 감소하고 최대 69% 감소
- 혈액 내 PCSK9 단백질 수준의 용량 의존적 감소
- 치료와 관련된 심각한 부작용 없음
- ALT 또는 혈소판의 임상적으로 중요한 변화 없음
회사는 2025년 하반기에 최종 용량 상승 데이터를 발표하고, 2상 시험을 시작하며, Eli Lilly의 PCSK9 프로그램 옵트인에 대한 결정을 받을 계획입니다. 현재 자금은 2027년 중반까지 지속될 것으로 예상됩니다.
Verve Therapeutics a annoncé des données initiales positives de l'essai clinique Heart-2 de phase 1b pour VERVE-102, un traitement d'édition de base en dose unique ciblant le PCSK9 pour les maladies cardiovasculaires. L'essai a inclus 14 participants atteints d'hypercholestérolémie familiale hétérozygote (HeFH) et/ou de maladie coronarienne prématurée (CAD).
Les résultats clés de trois cohortes de dosage (0,3, 0,45 et 0,6 mg/kg) ont montré:
- Une réduction moyenne du LDL-C de 53% et une réduction maximale de 69% dans la cohorte de 0,6 mg/kg
- Des diminutions dépendantes de la dose des niveaux de protéine PCSK9 dans le sang
- Aucun événement indésirable grave lié au traitement
- Aucune modification cliniquement significative des ALT ou des plaquettes
L'entreprise prévoit d'annoncer les données finales sur l'escalade des doses au second semestre 2025, de lancer des essais de phase 2 et de recevoir la décision d'Eli Lilly concernant leur programme d'option PCSK9. Le financement actuel devrait durer jusqu'à la mi-2027.
Verve Therapeutics hat positive erste Daten aus der Heart-2 Phase 1b-Studie zu VERVE-102 bekannt gegeben, einer Einzeldosis-Basiseditierungstherapie, die auf PCSK9 zur Behandlung von Herz-Kreislauf-Erkrankungen abzielt. Die Studie umfasste 14 Teilnehmer mit heterozygotem familiärem Hypercholesterinämie (HeFH) und/oder vorzeitiger koronarer Herzkrankheit (CAD).
Die wichtigsten Ergebnisse aus drei Dosierungsgruppen (0,3, 0,45 und 0,6 mg/kg) zeigten:
- Eine durchschnittliche LDL-C-Reduktion von 53% und eine maximale Reduktion von 69% in der 0,6 mg/kg-Gruppe
- Dosisabhängige Abnahmen der PCSK9-Proteinwerte im Blut
- Keine schwerwiegenden behandlungsbezogenen unerwünschten Ereignisse
- Keine klinisch signifikanten Veränderungen bei ALT oder Thrombozyten
Das Unternehmen plant, im zweiten Halbjahr 2025 die endgültigen Daten zur Dosiserhöhung bekannt zu geben, Phase-2-Studien zu starten und die Entscheidung von Eli Lilly zu ihrem PCSK9-Programm zu erhalten. Die derzeitige Finanzierung wird voraussichtlich bis Mitte 2027 ausreichen.
- Strong efficacy with 53% mean LDL-C reduction in highest dose cohort
- Excellent safety profile with no serious adverse events
- Dose-dependent response demonstrated across all cohorts
- FDA IND clearance received for U.S. trial sites
- Sufficient funding secured through mid-2027
- Phase 1b trial still ongoing with participant number (14)
- Final results not expected until second half of 2025
- Eli Lilly's opt-in decision pending, creating partnership uncertainty
Insights
Verve Therapeutics reports compelling initial data from their Heart-2 Phase 1b trial of VERVE-102, showing dose-dependent reductions in both PCSK9 and LDL-C levels. The highest dose cohort (0.6 mg/kg) achieved a mean LDL-C reduction of 53% with a maximum reduction of 69% in a single participant. When analyzed by total RNA dose, participants receiving 50-60mg demonstrated a mean LDL-C reduction of 59%.
The safety profile appears particularly promising - no treatment-related serious adverse events occurred across all 14 participants, with only one Grade 2 infusion reaction that resolved with acetaminophen. Importantly, no clinically significant changes in liver enzymes or platelets were observed at any dose level.
This data validates Verve's proprietary GalNAc-LNP delivery technology and positions VERVE-102 competitively against existing PCSK9 inhibitors that require regular dosing. The one-and-done approach addresses the significant medication adherence problem in cardiovascular disease management, where approximately half of patients discontinue prescribed lipid-lowering therapy within a year.
The company has clear execution plans with FDA IND clearance secured, enrollment ongoing in the fourth dose cohort (0.7 mg/kg), and sufficient capital to fund operations into mid-2027. The pending Eli Lilly opt-in decision expected in H2 2025 represents a significant near-term catalyst that could substantially enhance Verve's development capabilities and commercialization prospects.
These Heart-2 trial results represent a potential paradigm shift in hypercholesterolemia management. The 53-59% LDL-C reduction demonstrated by VERVE-102 approaches the efficacy of established PCSK9 monoclonal antibodies like evolocumab and alirocumab, which typically reduce LDL-C by 55-60% but require biweekly or monthly injections indefinitely.
What differentiates VERVE-102 is the permanent genetic modification of PCSK9 expression through base editing delivered via a single infusion. This approach directly addresses the well-documented medication adherence challenge that compromises real-world outcomes in cardiovascular disease management.
The dose-response relationship observed across cohorts provides valuable insights for optimizing the therapeutic window. Particularly encouraging is that each participant receiving ≥50mg total RNA achieved >50% LDL-C reduction, suggesting reliable clinical response at higher doses.
For HeFH and premature CAD patients who require lifelong lipid management, a single-treatment approach could revolutionize care standards while potentially improving outcomes by eliminating the adherence variable. The clean safety profile observed thus far - particularly the absence of liver enzyme elevations or platelet effects - is reassuring regarding the GalNAc-LNP delivery system.
The company's planned progression to Phase 2 in H2 2025 with inclusion of US trial sites following FDA IND clearance represents appropriate advancement timelines based on these encouraging results.
Single infusion of VERVE-102 led to dose-dependent decreases in blood PCSK9 and LDL-C, with mean reduction in LDL-C of
VERVE-102 was well-tolerated with no treatment-related serious adverse events and no clinically significant changes in ALT or platelets observed at any dose level among 14 participants
VERVE-102 utilizes a proprietary GalNAc-LNP which has demonstrated a potentially best-in-class safety profile
In the second half of 2025, Verve expects to report final Heart-2 dose escalation data, dose the first patient in a Phase 2 clinical trial for VERVE-102, and receive a decision from Eli Lilly and Company for the PCSK9 opt-in
Company to host conference call and webcast today, Monday, April 14, 2025, at 8 a.m. ET
BOSTON, April 14, 2025 (GLOBE NEWSWIRE) -- Verve Therapeutics, a clinical-stage company developing a new class of genetic medicines for cardiovascular disease, today announced positive initial data from the Heart-2 Phase 1b clinical trial of VERVE-102. The Heart-2 Phase 1b clinical trial is evaluating patients with heterozygous familial hypercholesterolemia (HeFH) and/or premature coronary artery disease (CAD), two populations that require deep and durable reductions of low-density lipoprotein cholesterol (LDL-C) levels in the blood. Among 14 participants across three dose levels, VERVE-102 was well-tolerated, with no treatment-related serious adverse events (SAEs) and no clinically significant laboratory abnormalities observed. A single infusion of VERVE-102 led to dose-dependent decreases in blood PCSK9 protein levels and LDL-C, with a mean reduction in blood LDL-C of
“These initial Heart-2 data are promising with respect to both safety and efficacy and suggest the potential for a new era of cardiovascular disease treatment where a single dose might lead to lifelong control of LDL-C,” said Eugene Braunwald, M.D., Distinguished Hersey Professor of Medicine at Harvard Medical School and Founding Chairman, TIMI Study Group, Brigham and Women’s Hospital. “Despite existing treatments to lower LDL-C, atherosclerotic cardiovascular disease (ASCVD) remains the most frequent cause of death worldwide. The reduction of ASCVD risk depends on both the magnitude of LDL-C reduction as well as the duration. With existing treatments, approximately half of patients discontinue their prescribed lipid lowering therapy within one year, resulting in poor real-world control of LDL-C. VERVE-102 holds great promise to transform the care of ASCVD and move that care from daily pills or intermittent injections over decades to a one dose future for sustained LDL-C lowering.”
VERVE-102
VERVE-102 is a novel, in vivo, investigational base editing medicine designed to be a single-course treatment that permanently turns off the PCSK9 gene in the liver and durably reduces disease-driving LDL-C. VERVE-102 consists of an adenine base editor and a guide RNA (gRNA) targeting the PCSK9 gene. Both are encapsulated in a lipid nanoparticle (LNP) and administered as a single intravenous infusion over two to four hours. VERVE-102 uses Verve’s proprietary GalNAc-LNP delivery technology, which is designed to allow the LNP to access liver cells using either the low-density lipoprotein receptor (LDLR) or the asialoglycoprotein receptor (ASGPR).
Heart-2 Clinical Trial Design
The Heart-2 clinical trial is an open-label Phase 1b clinical trial designed to evaluate the safety and tolerability of VERVE-102 administration in adult patients with HeFH and/or premature CAD who require additional lowering of LDL-C. The trial is a single-ascending dose study and endpoints include pharmacokinetics and changes in blood LDL-C and PCSK9 protein levels. HeFH is diagnosed based on high LDL-C levels, a personal or family history of ASCVD, physical exam features, and/or mutations identified in certain genes. Premature CAD is defined as evidence of CAD (heart attack, coronary revascularization procedure, or coronary atherosclerosis on imaging) occurring in men ≤ 55 years old or women ≤ 65 years old.
The Heart-2 clinical trial is expected to include four dose cohorts, each comprised of three to nine participants with HeFH and/or premature CAD. Initial data reported today are from 14 participants across the first three cohorts (weight-based cohorts of 0.3 mg/kg, 0.45 mg/kg, and 0.6 mg/kg) with at least 28 days of follow-up for each participant as of a data cutoff date of March 13, 2025.
Heart-2 Safety and Tolerability
VERVE-102 has been well-tolerated, with no treatment-related SAEs, no dose-limiting toxicities, and no cardiovascular events observed. Across all 14 participants, there was one infusion related reaction (Grade 2) which involved transient symptoms that resolved with acetaminophen. No clinically significant changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, or platelets were observed at any dose level. There were no dose-dependent trends in any of these laboratory measurements.
Heart-2 Efficacy Analysis
Following a single infusion of VERVE-102, dose-dependent reductions in two pharmacodynamic (PD) measures were observed: blood LDL-C and PCSK9 protein levels. Of note, in this patient population, LDL-C is a validated surrogate endpoint for clinical benefit accepted by the U.S. Food and Drug Administration (FDA) and other regulatory agencies.
Mean blood LDL-C and PCSK9 protein reductions from baseline, using a time-averaged percent change from day 28 through the last available follow-up, were as follows:
- Cohort 1; 0.3 mg/kg (n=4): LDL-C reduction was
21% and PCSK9 reduction was46% . - Cohort 2; 0.45 mg/kg (n=6): LDL-C reduction was
41% and PCSK9 reduction was53% . - Cohort 3; 0.6 mg/kg (n=4): LDL-C reduction was
53% and PCSK9 reduction was60% .
Among the 14 participants, a maximum LDL-C reduction of
For LNP-delivered in vivo gene editing medicines, total RNA dose administered is emerging as a key driver of PD. As such, Verve also evaluated the Heart-2 PD data by total RNA dose. The analysis includes the 14 participants in the Heart-2 clinical trial grouped into three ranges of total RNA dose administered: < 25 mg (n=4), 25 – < 50 mg (n=7), and 50 – < 60 mg (n=3).
Mean LDL-C reductions from baseline, using a time-averaged percent change from day 28 through the last available follow-up, were as follows:
| VERVE-102 total RNA dose range | < 25 mg | 25 – < 50 mg | 50 – < 60 mg |
| Participants, n | 4 | 7 | 3 |
| Mean total RNA dose | 20 mg | 37 mg | 55 mg |
| Mean LDL-C % reduction from baseline | - | - | - |
Across all 14 participants, VERVE-102 demonstrated a strong dose-dependent response between the amount of total RNA administered and LDL-C reductions. Three participants received a total RNA dose between 50 and 60 mg, with an average dose received of 55 mg of total RNA. In this dose group, VERVE-102 demonstrated a time-averaged LDL-C mean reduction of
“Verve was founded seven years ago with a vision of one treatment dose potentially leading to a lifetime of LDL-C lowering. The data presented today suggest that this game-changing, one dose future is possible,” said Sekar Kathiresan, M.D., co-founder and chief executive officer of Verve Therapeutics. “We are pleased by the safety VERVE-102 has demonstrated so far, and our proprietary GalNAc-LNP delivery technology is showing a potentially best-in-class safety profile. The initial efficacy data suggest that VERVE-102 has the potential to match or exceed the LDL-C reduction provided by currently available PCSK9-targeting therapies. Among participants who received a dose greater than 50 mg total RNA, we observed a mean LDL-C reduction of
Dr. Kathiresan continued, “In sum, VERVE-102 has the potential to solve the urgent need for enduring efficacy in patients living with HeFH or ASCVD. We are incredibly grateful to the patients and healthcare professionals who believe in our mission and participate in our clinical trials. Together, we are striving to revolutionize cardiovascular disease treatment and deliver a one dose future.”
Next Steps
The Heart-2 clinical trial is enrolling participants in the fourth dose cohort of 0.7 mg/kg in the United Kingdom, Canada, Israel, Australia, and New Zealand. As of April 7, 2025, Verve has dosed two participants in this cohort. The early laboratory and clinical safety profile is in line with the first three cohorts. Verve expects to announce the final data from the dose escalation portion of the Heart-2 clinical trial, including durability data, in the second half of 2025.
Verve plans to dose the first patient in the Phase 2 clinical trial of VERVE-102 in the second half of 2025, subject to regulatory clearance. With the recent clearance by the U.S. FDA of the investigational new drug (IND) application for VERVE-102, Verve expects to enroll patients at U.S. trial sites in the Phase 2 clinical trial. Verve expects its current capital position to be sufficient to fund its operations into mid-2027, which includes the completion of the Phase 2 clinical trial.
Under the PCSK9 program collaboration agreement with Verve, Eli Lilly and Company (Lilly) holds the right to opt-in to share worldwide development expenses (
Conference Call Information
Verve will host a conference call and webcast today, Monday, April 14, 2025, at 8 a.m. ET to review the initial Heart-2 clinical data. The conference call can be accessed via this link: https://register-conf.media-server.com/register/BI2d0a1d3cccc6461f95e6d7f836157a60. A live webcast will also be available under Events in the Investors section of the company’s website at https://ir.vervetx.com/events. The archived webcast will be available on the company’s website beginning approximately two hours after the event.
About Verve Therapeutics
Verve Therapeutics, Inc. (Nasdaq: VERV) is a clinical-stage company developing a new class of genetic medicines for cardiovascular disease with the potential to transform treatment from chronic therapies to single-course gene editing medicines. The company’s lead programs – VERVE-102, VERVE-201, and VERVE-301 – target the three cholesterol drivers of atherosclerosis: LDL-C, remnant cholesterol, and Lp(a). VERVE-102 is designed to permanently turn off the PCSK9 gene in the liver and is being developed initially for heterozygous familial hypercholesterolemia (HeFH) and ultimately to treat patients with established atherosclerotic cardiovascular disease (ASCVD) who continue to be impacted by high LDL-C levels. VERVE-201 is designed to permanently turn off the ANGPTL3 gene in the liver and is initially being developed for refractory hypercholesterolemia, where patients still have high LDL-C despite treatment with maximally tolerated standard of care therapies, and homozygous familial hypercholesterolemia (HoFH). VERVE-301 is designed to permanently turn off the LPA gene to reduce Lp(a) levels. Lp(a) is a genetically validated, independent risk factor for ASCVD, ischemic stroke, thrombosis, and aortic stenosis. For more information, please visit www.VerveTx.com.
Cautionary Note Regarding Forward Looking Statements
This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties, including statements regarding the company’s ongoing Heart-2 clinical trial; the timing and availability of data for the Heart-2 trial and timing for initiation of the Phase 2 clinical trial for VERVE-102; the timing for delivery of the opt-in package and of Lilly’s decision for the PCSK9 program; the potential advantages and therapeutic potential of VERVE-102 and the period over which the company believes that its cash, cash equivalents and marketable securities will be sufficient to fund its operating expenses. All statements, other than statements of historical facts, contained in this press release, including statements regarding the company’s strategy, future operations, future financial position, prospects, plans and objectives of management, are forward-looking statements. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in, or implied by, such forward-looking statements. These risks and uncertainties include, but are not limited to, risks associated with the company’s limited operating history; the company’s ability to timely submit and receive approvals of regulatory applications for its product candidates; advance its product candidates in clinical trials; initiate, enroll and complete its ongoing and future clinical trials on the timeline expected or at all; correctly estimate the potential patient population and/or market for the company’s product candidates; replicate in clinical trials positive results found in preclinical studies and/or earlier-stage clinical trials of VERVE-101, VERVE-102, and VERVE-201; advance the development of its product candidates under the timelines it anticipates in current and future clinical trials; obtain, maintain or protect intellectual property rights related to its product candidates; manage expenses; and raise the substantial additional capital needed to achieve its business objectives. For a discussion of other risks and uncertainties, and other important factors, any of which could cause the company’s actual results to differ from those contained in the forward-looking statements, see the “Risk Factors” section, as well as discussions of potential risks, uncertainties and other important factors, in the company’s most recent filings with the Securities and Exchange Commission and in other filings that the company makes with the Securities and Exchange Commission in the future. In addition, the forward-looking statements included in this press release represent the company’s views as of the date hereof and should not be relied upon as representing the company’s views as of any date subsequent to the date hereof. The company anticipates that subsequent events and developments will cause the company’s views to change. However, while the company may elect to update these forward-looking statements at some point in the future, the company specifically disclaims any obligation to do so.
Investor Contact
Jen Robinson
Verve Therapeutics, Inc.
jrobinson@vervetx.com
Media Contact
Ashlea Kosikowski
1AB
ashlea@1abmedia.com
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