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Thursday, May 5, 2022

Arcturus Reports Three-Month Durability Results From ARCT-154 COVID-19 Booster Trial

 

  • Arcturus Therapeutics Holdings Inc  provided updated data from its Phase 1/2 booster clinical trial showing the durability of antibody response with ARCT-154 for at least three months after a low-dose (5 mcg) booster.
  • The study also exhibited that booster vaccination generated strong immune responses, both with respect to response magnitude and duration of response for at least three months post-boost. 
  • Twelve participants in this arm received 5 mcg of ARCT-154 at least five months after receiving two primary doses of Pfizer Inc  - BioNTech SE's  Comirnaty. 
  • Results show that a single 5 mcg dose of ARCT-154 led to neutralizing antibody responses that remained 30-fold elevated over baseline (pre-boost) levels at three months after vaccination. 
  • 28-fold and 40-fold increases in neutralizing antibody responses from baseline levels were seen on Day 15 and Day 29.
  • Data for Beta strain also demonstrated notable durability of neutralizing antibody response with 24-fold at three months after booster vaccination, compared to 26-fold and 31-fold over baseline on Day 15 and Day 29, respectively.

Dynavax's Adjuvant-Based Bivalent COVID-19 Vaccine Candidate Shows Encouraging Preclinical Action

 

  • Clover Biopharmaceuticals Ltd announced new promising data from a preclinical study on its bivalent vaccine candidate, which combines the trimeric spike antigens from the original SARS-CoV-2 strain and the omicron variant. 
  • Clover developed the SCB-2019 antigen, a stabilized trimeric form of the S-protein based on the original strain of the SARS-CoV-2 virus. It includes Dynavax Technologies Corporation's  CpG 1018 advanced adjuvant and aluminum hydroxide. 
  • In a preclinical study, the bivalent vaccine candidate elicited broad neutralization against all Variants of Concern (VoC), including omicron, in primary vaccination and booster settings. 
  • Notably, compared to the monovalent omicron variant vaccine (SCB-2022B) alone, the bivalent COVID-19 vaccine demonstrated higher neutralization levels against most of the variants tested and comparable levels against omicron.
  • Clover expects to initiate a Phase 1 trial in Q2 evaluating SCB-2020S (a prototype and beta-variant chimeric vaccine candidate) to demonstrate proof-of-concept for variant strain change utilizing the Trimer-Tag platform.

US Study Shows Omicron As Severe As Previous COVID Variants

 

  • A large U.S. study has found that the omicron variant of the SARS-CoV2 virus is intrinsically as severe as previous variants, unlike assumptions made in earlier studies that it was more transmissible but less severe, Reuters report.
  • "We found that the risks of hospitalization and mortality were nearly identical between periods," said four scientists who conducted the study based on records of 130,000 COVID-19 patients, referring to times in the past two years when different variants were dominant.
  • The studies that assumed that the omicron variant was less severe were conducted in various places, including South Africa, Scotland, England, and Canada.
  • They said their study could have several limitations, including the possibility that it underestimated the number of vaccinated patients in more recent COVID waves and the total number of infections because it excluded patients who performed at-home rapid tests.

Young Cancer Survivors Face Higher Risk of Death From Second Malignancies

 Adolescent and young adult (AYA) cancer survivors have a significantly increased risk for developing a new cancer and dying from that cancer, according to a population-based study.

These younger cancer survivors had a 25% higher risk for cancer incidence, and an 84% higher risk for cancer death, compared with the general population, reported Hyuna Sung, PhD, of the American Cancer Society, and colleagues.

Among over 170,000 survivors ages 15 to 39 at the time of first primary diagnosis who had survived for at least 5 years, 13,420 subsequent primary cancers, and 5,008 deaths, occurred over a mean follow-up of 14.6 years, they noted in the Journal of the National Cancer Institute.

"Research on subsequent primary cancers has mainly focused on pediatric cancer survivors," Sung told MedPage Today. "This study highlights the need for targeted prevention strategies not only for pediatric cancer survivors, but AYA survivors as well."

Breast cancer accounted for 17.8% of subsequent primary cancers, followed by lung (10.8%), colorectal (7.6%), and prostate (7.1%) cancers. Lung cancer was the leading cause of death (23.7%), followed by breast (8.6%), colorectal (6.9%), and pancreatic (6.8%) cancers.

The overall risk of developing a subsequent primary cancer was statistically significantly higher for 20 of the 29 index cancers evaluated in the study, and remained elevated for 20 or more years postdiagnosis for nine of the cancers. The mortality risk was statistically significantly higher for 26 cancers, and remained elevated for 20 or more years after diagnosis for 20 of the cancers.

Of the four most common index cancers, the risk of developing a subsequent primary cancer compared with the general population was significantly higher for breast cancer (standardized incidence ratio [SIR] 1.31, absolute excess incidence [AEI] 12.1 per 10,000) and testicular cancer (SIR 1.21, AEI 7.9 per 10,000). This risk was not different among thyroid cancer survivors, and was statistically significantly lower among melanoma survivors (SIR 0.87, AEI -6.2 per 10,000).

Similarly, the risk of dying from a subsequent primary cancer was significantly elevated among breast cancer survivors (standardized mortality ratio [SMR] 1.79, absolute excess mortality [AEM] 9.2 per 10,000) and testicular cancer survivors (SMR 1.74, AEM 7.8 per 10,000), with no difference among thyroid cancer and melanoma survivors.

For individual cancers, the highest SIRs were for females with Hodgkin lymphoma (SIR 3.05), males with Kaposi sarcoma (SIR 2.58), and males with Hodgkin lymphoma (SIR 2.24), with cumulative incidence rates after 35 years of 25.9%, 13.7%, and 18.8%, respectively.

The highest SMRs were seen for small intestine cancer (SMR 6.97), eye cancer (SMR 6.53), and anal cancer (SMR 6.34).

For this study, Sung and colleagues used population-based cancer incidence and mortality data from nine Surveillance, Epidemiology, and End Results Program (SEER) registries. Follow-up began 5 years from initial cancer diagnosis and continued until censoring at death, loss to follow-up, or Dec. 31, 2018, whichever came first, while the cumulative incidence and mortality rates of subsequent primary cancers were calculated at 35 years after the index cancer diagnosis.

Even with long-term follow-up, events were rare for some subsequent primary cancers, the authors noted. In addition, restricting the analysis to subsequent cancers that occurred 5 or more years after the initial diagnosis "likely underestimated" the risk for some cancers, "particularly treatment-related acute myeloid leukemia or myelodysplastic syndromes, which typically arise after a short-term latency," they wrote.

As for future areas of research, Sung said that while the study quantified risk estimates, "they should be refined based on treatment history and potential cancer risk factors. There should also be more research to develop models to deliver more equitable and survivor-centric care."


Disclosures

This study was supported by the Intramural Research Department of the American Cancer Society, and by a grant from the American Cancer Society and the Medical College of Wisconsin Cancer Center.

The authors reported no disclosures.