Dynavax Announces Positive Topline Phase 1/2 Results Supporting Potential Best-in-Class Shingles Vaccine Profile
Dynavax Technologies (Nasdaq: DVAX) announced positive topline results from Part 1 of its Phase 1/2 clinical trial for Z-1018, its novel shingles vaccine candidate, demonstrating comparable efficacy to Shingrix with better tolerability. The trial's selected dose achieved a 100% humoral vaccine response rate and 89.7% cellular immune response rate.
Z-1018 showed significantly lower adverse reactions compared to Shingrix, with only 12.5% reporting grade 2-3 local reactions versus 52.6% for Shingrix, and 27.5% reporting grade 2-3 systemic reactions versus 63.2% for Shingrix. The company will advance the 100 mcg dose with CpG 1018 and alum adjuvant using an 8-week dosing interval to Part 2 of the trial in adults 70+ years, scheduled for 2H 2025.
Dynavax Technologies (Nasdaq: DVAX) ha annunciato risultati positivi di topline dalla Parte 1 dello studio clinico di Fase 1/2 per Z-1018, il suo nuovo candidato vaccino contro l'herpes zoster, che ha mostrato un'efficacia paragonabile a Shingrix e una migliore tollerabilità. La dose selezionata ha raggiunto un tasso di risposta umorale del 100% e un tasso di risposta immunitaria cellulare del 89,7%.
Z-1018 ha prodotto reazioni avverse significativamente inferiori rispetto a Shingrix: solo il 12,5% ha riportato reazioni locali di grado 2-3 rispetto al 52,6% con Shingrix, e il 27,5% ha riportato reazioni sistemiche di grado 2-3 rispetto al 63,2% con Shingrix. L'azienda porterà avanti la dose da 100 mcg con CpG 1018 e adiuvante alluminio, somministrata con intervallo di 8 settimane, nella Parte 2 dello studio in adulti di età pari o superiore a 70 anni, prevista per la seconda metà del 2025.
Dynavax Technologies (Nasdaq: DVAX) anunció resultados positivos provisionales de la Parte 1 de su ensayo clínico de Fase 1/2 para Z-1018, su nuevo candidato vacunal contra el herpes zóster, mostrando una eficacia comparable a Shingrix y mejor tolerabilidad. La dosis seleccionada alcanzó una tasa de respuesta humoral del 100% y una tasa de respuesta inmune celular del 89,7%.
Z-1018 presentó reacciones adversas significativamente menores frente a Shingrix: solo el 12,5% informó reacciones locales de grado 2-3 frente al 52,6% de Shingrix, y el 27,5% informó reacciones sistémicas de grado 2-3 frente al 63,2% de Shingrix. La compañía avanzará con la dosis de 100 mcg con CpG 1018 y adyuvante de aluminio, administrada con un intervalo de 8 semanas, a la Parte 2 del ensayo en adultos de 70 años o más, programada para la segunda mitad de 2025.
Dynavax Technologies (Nasdaq: DVAX)는 대상포진 백신 후보 Z-1018의 1/2상 임상시험 1부에서 긍정적 톱라인 결과를 발표했습니다. Z-1018은 Shingrix와 유사한 효능을 보이면서 내약성이 더 우수했습니다. 선정된 용량은 체액성 항체 반응률 100% 및 세포성 면역 반응률 89.7%를 달성했습니다.
Z-1018은 Shingrix에 비해 이상반응이 현저히 적었으며, 국소 2-3등급 반응을 보고한 비율은 12.5%로 Shingrix의 52.6%에 비해 낮았고, 전신 2-3등급 반응은 27.5%로 Shingrix의 63.2%보다 적었습니다. 회사는 CpG 1018 및 알루미늄 보조제를 포함한 100 mcg 용량을 8주 간격으로 투여하는 방식으로 70세 이상 성인을 대상으로 한 2부 시험으로 진행할 예정이며, 일정은 2025년 하반기입니다.
Dynavax Technologies (Nasdaq: DVAX) a annoncé des résultats topline positifs de la Partie 1 de son essai clinique de phase 1/2 pour Z-1018, son candidat vaccin contre le zona, montrant une efficacité comparable à Shingrix avec une meilleure tolérabilité. La dose retenue a obtenu un taux de réponse humorale de 100% et un taux de réponse immunitaire cellulaire de 89,7%.
Z-1018 a entraîné significativement moins d'effets indésirables que Shingrix : seulement 12,5% ont rapporté des réactions locales de grade 2-3 contre 52,6% pour Shingrix, et 27,5% ont rapporté des réactions systémiques de grade 2-3 contre 63,2% pour Shingrix. La société fera progresser la dose de 100 mcg avec CpG 1018 et adjuvant alumine, administrée avec un intervalle de 8 semaines, en Partie 2 de l'essai chez les adultes de 70 ans et plus, prévue au second semestre 2025.
Dynavax Technologies (Nasdaq: DVAX) gab positive Topline-Ergebnisse aus Teil 1 der Phase‑1/2-Studie zu Z-1018 bekannt, dem neuen Impfstoffkandidaten gegen Gürtelrose. Z-1018 zeigte eine vergleichbare Wirksamkeit zu Shingrix bei besserer Verträglichkeit. Die ausgewählte Dosis erreichte eine humorale Antwortrate von 100% und eine zelluläre Immunantwortrate von 89,7%.
Z-1018 wies deutlich weniger unerwünschte Reaktionen als Shingrix auf: nur 12,5% meldeten lokale Reaktionen Grad 2–3 gegenüber 52,6% bei Shingrix, und 27,5% meldeten systemische Reaktionen Grad 2–3 gegenüber 63,2% bei Shingrix. Das Unternehmen wird die 100‑µg‑Dosis mit CpG 1018 und Aluminium‑Adjuvans in einem 8‑Wochen‑Intervall in Teil 2 der Studie bei Erwachsenen ab 70 Jahren weiterführen, geplant für das 2. Halbjahr 2025.
- None.
- Phase 2 trials in elderly population (70+) still pending
- Cellular immune response rate slightly lower than Shingrix (89.7% vs 93.5%)
- Full Phase 3 development program still required before potential commercialization
Insights
Dynavax's shingles vaccine Z-1018 shows comparable efficacy to market leader Shingrix with significantly better tolerability profile, potentially disrupting a multi-billion-dollar market.
Dynavax's Phase 1/2 trial results for their shingles vaccine candidate Z-1018 represent a significant breakthrough in vaccine development. The data shows 100% humoral vaccine response rate with the selected dose formulation compared to 96.9% for Shingrix, and 89.7% cellular immune response versus 93.5% for Shingrix. These robust immunological responses are comparable to the current market-leading vaccine.
What's truly impressive is the substantially improved tolerability profile. At the selected dose, only 12.5% of participants reported grade 2-3 local post-injection reactions versus 52.6% for Shingrix, and 27.5% reported grade 2-3 systemic reactions compared to 63.2% for Shingrix. This represents a more than 50% reduction in adverse reactions, addressing one of the major barriers to shingles vaccination adoption.
The company has strategically selected the 100 mcg dose with CpG 1018 adjuvant plus alum using an 8-week dosing interval for advancement to the elderly population (70+) in Part 2 of the trial. This population is particularly important as cellular immunity declines with age, making them more susceptible to shingles reactivation. The strong T-cell responses seen in this trial (median CD4+ T-cell frequency over 1200 per million in the selected formulation) are especially promising for efficacy in older adults.
With Shingrix generating over $3 billion in annual sales despite its reactogenicity issues, Dynavax has identified a clear market opportunity. If Z-1018 maintains this favorable efficacy/tolerability balance through Phase 3 trials, it could significantly disrupt the current monopoly in the shingles vaccine market, potentially driving broader vaccination rates and substantial revenue for Dynavax.
- At all doses and formulations evaluated in Part 1 of the trial, Z-1018 was well-tolerated and demonstrated a favorable tolerability profile, including lower solicited local and systemic post-injection reactions, versus Shingrix
- Z-1018 demonstrated robust immune responses in all dose arms, including a
100% humoral vaccine response rate at the dose selected for advancement, with comparable immunogenicity to Shingrix - Dynavax selects the optimal dose of Z-1018 for advancement to Part 2 of Phase 1/2 trial in adults 70 years of age and older, expected to initiate in 2H 2025
In Part 1 of the trial at one month after the second vaccine dose, Z-1018 demonstrated antibody and CD4⁺ T cell vaccine responses similar to those observed in the comparator arm receiving Shingrix, the currently licensed shingles vaccine, with a favorable tolerability profile. At the dose formulation and regimen chosen for advancing to Part 2 of the trial, Z-1018 achieved a
Z-1018 was also well-tolerated with a favorable safety profile in the study. Z-1018 exhibited low rates of grade 2 and 3 solicited local and systemic post-injection reactions (PIRs) in all dose, formulation, and dosing regimen arms. At the dose formulation and regimen chosen for advancement to Part 2 of the trial,
"These positive data mark an important inflection point for our novel shingles vaccine program as we strive to develop a product with a potential best-in-class profile with the aim to disrupt the multi-billion-dollar shingles vaccine market, which is currently dominated by one product," said Ryan Spencer, Chief Executive Officer of Dynavax. "We met our goal for this study, as the results show immune responses comparable to Shingrix, along with a favorable tolerability profile, and provide the basis for selecting the dose and regimen to advance into further development. Based on these findings, plans are underway to initiate Part 2 of the Phase 1/2 trial in the 70 and older population, an opportunity to further de-risk this program ahead of Phase 3 development."
Z-1018 is an investigational shingles vaccine utilizing the Dynavax-manufactured glycoprotein E (gE) antigen and is adjuvanted with CpG 1018, Dynavax's proprietary vaccine adjuvant. Part 1 of the Phase 1/2 trial was a randomized, observer-blinded, active-controlled, dose escalation, multicenter trial to evaluate the safety, tolerability, and immunogenicity of Z-1018 compared to Shingrix in healthy adult participants aged 50 through 69 years. A key objective of Part 1 was to evaluate three different dose levels of gE antigen (50 mcg, 100 mcg, 200 mcg) with two different adjuvant formulations (one with CpG 1018 alone and one with CpG 1018 plus alum), as well as 8-week and 12-week dosing regimens. The key safety endpoint was solicited local and systemic post-injection reactions (PIRs), measured for up to seven days following each dose. The key immunogenicity endpoints included vaccine response rates (VRR) for anti-gE IgG antibodies and gE-specific CD4+ T cells, assessed four weeks after the second study injection. VRRs were defined as participants with >4-fold increase in anti-gE IgG concentration and, separately, >2-fold increase in CD4⁺ T-cell frequency over baseline. A composite VRR comprised of participants with immune responses that met both antibody and T-cell criteria.
"We are very encouraged by the magnitude and consistency of the immune responses observed, particularly the robust CD4⁺ T cell activity for Z-1018 compared to Shingrix," said Robert Janssen, M.D., Chief Medical Officer of Dynavax. "Shingles is a painful disease driven by cellular immune decline with age. A vaccine that provides a strong immune response alongside favorable tolerability, compared to the current standard of care, could provide an important new option for protection against this debilitating disease."
Based on these results, Dynavax has selected the 100 mcg dose of gE antigen, adjuvanted with CpG 1018 and alum, and using an 8-week dosing interval, to advance into Part 2 of the Phase 1/2 trial. This study will evaluate adults 70 years of age and older to generate clinical proof-of-concept head-to-head versus Shingrix in this key population ahead of advancement into the pivotal program.
The table below summarizes topline immunogenicity results for the Z-1018 arms with the 100 mcg gE formulation, and 8-week dosing interval, compared to Shingrix:
Topline Immunogenicity Results Summary (1-Month Following Second Vaccine Dose)1
Outcome: | Z-1018 100mcg 8-week dosing (n = 31) | Z-1018 100mcg/alum 8-week dosing interval (n = 29) | Shingrix (n = 32) |
Vaccine Response Rate, Anti-gE | (88.8 - 100.0) | (88.1 - 100.0) | (83.8 - 99.9) |
Vaccine Response Rate, CD4+ T-cells | (70.2 - 96.4) | (72.6 - 97.8) | (78.6 - 99.2) |
Vaccine Response Rate, Composite | (70.2 - 96.4) | (72.6 - 97.8) | (74.2 - 98.0) |
Geometric Mean Concentration of | 63.5 (51.0 - 79.1) | 73.8 (59.4 - 91.7) | 71.7 (58.7 - 87.5) |
Geometric Mean Fold Increase of | 49.6 (39.8 - 61.8) | 57.7 (46.4 - 71.6) | 56.0 (45.9 - 68.4) |
Median Frequency of Activated gE- | 903.3 (558.4, 1359.7) | 1256.7 [709.7, 1609] | 1428.3 [891.2, 2318.5] |
1 Per Protocol Population includes participants receiving both study doses
Topline tolerability results for these study arms are outlined in the following table:
Topline Tolerability Results Summary2
Rate of Participants with | Z-1018 100mcg 8-week dosing (n=40) | Z-1018 100mcg/alum 8-week dosing (n=40) | Shingrix (n=38) |
Local PIRs | 7 ( | 5 ( | 20 ( |
Systemic PIRs | 7 ( | 11 ( | 24 ( |
2 Safety Population includes all subjects receiving at least one study dose
About Shingles
Herpes zoster, or shingles, is caused by reactivation of the varicella-zoster virus and affects approximately 1 in 3 people in their lifetime. The disease is characterized by a painful rash and can lead to serious complications, particularly in older adults. Despite the availability of an effective vaccine, there remains a need for broader access and improved tolerability.
About Z-1018
Z-1018 is an investigational non-live, recombinant subunit vaccine in development for the prevention of shingles in adults 50 and over. It combines an antigen, glycoprotein E, with Dynavax's proprietary adjuvant system, CpG 1018, and alum and may help overcome the natural age-related decline in responses to immunization that contributes to the challenge of protecting adults aged 50 and over from shingles.
About Dynavax
Dynavax is a commercial-stage biopharmaceutical company developing and commercializing innovative vaccines to help protect the world against infectious diseases. Dynavax has two commercial products, HEPLISAV-B® vaccine [Hepatitis B Vaccine (Recombinant), Adjuvanted], which is approved in the
Forward-Looking Statements
This press release contains "forward-looking" statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, which are subject to a number of risks and uncertainties. All statements that are not historical facts are forward-looking statements. Forward-looking statements can generally be identified by the use of words such as "anticipate," "believe," "continue," "could," "estimate," "expect," "forecast," "intend," "will," "may," "plan," "potential," "would" and similar expressions, or the negatives thereof, or they may use future dates. Forward-looking statements made in this document include statements regarding the expected initiation of Part 2 of the Phase 1/2 trial and anticipated benefits from Part 2, the potential for Z-1018 to have a best-in-class profile and possibly disrupt the shingles vaccine market, and the possibility that a vaccine that provides a strong immune response alongside favorable tolerability, compared to the current standard of care, could provide an important new option for protection against shingles. Actual results may differ materially from those set forth in this press release due to the risks and uncertainties inherent in Dynavax's business, including, the risk risks related to the timing of initiation, completion and results of planned clinical studies, risks related to the development and pre-clinical and clinical testing of vaccines containing CpG 1018 adjuvant, as well as other risks detailed in the "Risk Factors" section of its Quarterly Report on Form 10-Q for the three months ended June 30, 2025 and periodic filings made thereafter, as well as discussions of potential risks, uncertainties and other important factors in its other filings with the
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