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Narrow-spectrum Drug Shows Promise Against C Diff Infection In Phase 2 Trial

Yaroslav Astakhov/ iStock 

Targeting older adults with underlying health conditions—as opposed to the general population—for respiratory syncytial virus (RSV) vaccines would reduce spending and prevent illness, according to a modeling study yesterday in the Canadian Medical Association Journal (CMAJ).

The study compared the cost-effectiveness of different vaccine programs in different age groups with different medical risks. 

The model considered a population of 100,000 people aged 50 years and older. Vaccine characteristics were based on RSV vaccines authorized in Canada as of May 2024, with vaccine protection assumed to last 2 years. 

The cost-effectiveness threshold was $50,000 per quality-adjusted life year (QALY).

Optimal in oldest adults with underlying conditions

According to the study authors, without vaccination, they projected 131,389 (95% credible interval [CrI], 120,070 to 143,581) medically attended RSV cases, 12,068 (95% CrI, 10,324 to 13,883) hospital admissions, and 1,015 (95% CrI, 617 to 1,450) deaths annually among Canadians aged 60 years and older.

Vaccinating strategies based on age plus risk for RSV-related complications were projected to avert a median of 20% to 31% of outpatient cases, 38% to 42% of hospital cases, and 39% to 42% of deaths, the authors said.  Vaccines were most cost-effective, according to the model, when given to adults ages 70 and older, with one or more chronic medical condition.

We found that vaccination of older adults may be less costly and more effective than no vaccination.

"We found that vaccination of older adults may be less costly and more effective than no vaccination and that vaccinating people aged 70 years and older with chronic medical conditions is likely to be cost-effective based on commonly used cost-effectiveness thresholds," said Ashleigh Tuite, PhD from the Public Health Agency of Canada in a CMAJ press release.

"Strategies focused on adults with underlying medical conditions that place them at increased risk of RSV disease are more likely to be cost-effective than general age-based strategies," Tuite added. 

GSK Abandons Herpes Vaccine After Disappointing Phase I/II Proof-of-Concept Data

GSK on Wednesday announced that it is discontinuing the development of its early-stage herpes simplex virus vaccine, which will not advance to Phase III studies after failing the TH HSV REC-003 proof-of-concept study.

The pharma did not say what specific efficacy metric the vaccine candidate failed to satisfy, only revealing that it "did not meet the study's primary efficacy objective." The study found no safety concerns with the investigational shot, which was dubbed GSK3943104.

Highlighting the "unmet medical need and burden" in patients suffering from herpes simplex virus (HSV), GSK said that it will continue to collect safety and other follow-up data from TH HSV REC-003, which could "offer valuable insights into recurrent genital herpes." The company's findings will help the pharma "progress future research and development" of its HSV program.

According to GSK's pipeline page on its website, it has no more candidates for HSV.

TH HSV REC-003 was a randomized and observer-blinded study that was conducted in two parts: the first enrolled healthy volunteers between the ages of 18 to 40 years, while the second recruited patients with recurrent genital herpes, aged 18 to 60 years. According to its clinicaltrials.Gov page, the study tested three formulations of the vaccine candidate, with or without an adjuvant, against placebo. A total of 342 patients were enrolled in the trial.

The study's primary outcome was the proportion of patients that hit a "solicited administration site event," which include pain, redness and swelling, within seven days after the first vaccine dose, and then again after the second dose given at day 29. The study also evaluated systemic effects, such as fever, fatigue, headaches and muscle pain.

Aside from safety outcomes, TH HSV REC-003 also looked for signals of efficacy for the vaccine candidate, particularly in terms of confirmed HSV-2-related recurrent genital herpes episodes.

HSV is a common infection that often has no signs or causes only mild symptoms. In more severe cases, it can lead to painful and recurring blisters, while newly contracted infections can manifest as fevers, body aches and swollen lymph nodes. There are currently no cures or vaccines for HSV.

Moderna is advancing an HSV vaccine with its mRNA-based shot mRNA-1608, which is currently in a Phase I/II study in the U.S., according to a company announcement in March 2024. BioNTech is also developing an HSV vaccine, dubbed BNT163, which in December 2022 entered its first-in-human Phase I trial.

2 New Vaccines May Be First Step Toward Curing Brain Cancer

Bottle of Vaccine, treatment of Cancer (© Giovanni Cancemi - stock.Adobe.Com)

IRVINE, Calif. — In the world of cancer treatment, glioblastoma (GBM) stands out as one of the most challenging adversaries. This aggressive and deadly brain cancer, which mainly affects adults, has long been associated with grim survival rates despite advances in medical science. However, there's now a ray of hope on the horizon thanks to next-generation vaccines.

Researchers Robert Dillman and Daniela Bota from the University of California-Irvine explain that recent developments in vaccine technology are offering new possibilities for patients battling this disease. Two promising candidates, in particular, are capturing the attention of researchers and clinicians alike: SurVaxM and AV-GBM-1. These innovative approaches represent a significant step forward in the ongoing battle against glioblastoma. The findings are published in the journal Oncotarget.

"Vaccines have been considered a promising approach for GBM for many years," the researchers note in a media release.

Glioblastoma is a rare but lethal form of brain cancer that affects approximately 13,000 people in the United States each year. Despite aggressive treatment combining surgery, radiation, and chemotherapy, the outlook for patients has remained bleak. Most clinical trials in recent years have reported median survival times of around 16 months, with only about 25% of patients surviving for two years after diagnosis.

The search for more effective treatments has led scientists to explore the potential of cancer vaccines. Unlike traditional vaccines that prevent diseases, these therapeutic vaccines aim to stimulate the body's immune system to fight existing cancer cells. The concept is elegantly simple: train the immune system to recognize and attack cancer cells as if they were foreign invaders.

SurVaxM, one of the promising vaccine candidates, targets a protein called survivin that is commonly found in glioblastoma cells but rarely in healthy cells. This vaccine combines the survivin protein with other components that help boost the immune response. Early results from a phase 2 trial have been encouraging, with patients showing improved survival rates compared to historical data.

The other contender, AV-GBM-1, takes a more personalized approach. This vaccine is created using the patient's own immune cells and tumor tissue. By exposing the patient's immune cells to their unique tumor antigens, the vaccine aims to create a tailored immune response against the cancer. Initial results from a clinical trial of AV-GBM-1 have also shown promise, with some patients experiencing longer survival times than expected.

These vaccines represent a shift in how we approach glioblastoma treatment. Instead of relying solely on therapies that directly attack cancer cells, they harness the power of the body's own immune system to fight the disease. This approach not only has the potential to be more effective but may also lead to fewer side-effects compared to traditional treatments.

While these results are exciting, it's important to note that the journey from promising clinical trials to widely available treatments is often long and complex. Larger, randomized trials will still be necessary to confirm the effectiveness of these vaccines and to better understand which patients are most likely to benefit. Nevertheless, the emergence of these vaccine candidates offers a glimmer of hope in a field that has seen little progress in recent decades.

Methodology

The research into these new vaccine candidates involved carefully designed clinical trials. For SurVaxM, researchers selected newly diagnosed glioblastoma patients who had undergone complete tumor removal and completed initial radiation and chemotherapy. The vaccine was then administered through injections under the skin, along with additional immune-stimulating substances.

AV-GBM-1 took a different approach. Patients were enrolled before starting standard treatment. Researchers collected tumor tissue during surgery and used it to create a personalized vaccine for each patient. This vaccine was then given through injections after the patient had recovered from initial treatments.

Both studies carefully monitored patients for side effects and tracked how long they lived without the cancer progressing (progression-free survival) and overall survival time.

Key Results

The SurVaxM trial reported a median overall survival of 25.9 months from the time of diagnosis for the group of patients who received the vaccine. This is notably longer than the typical 16-month survival seen in many previous studies.

For AV-GBM-1, the median overall survival was 16.0 months from the time of enrollment in the study, with 33% of patients surviving for two years and 23% for three years. While these numbers may seem lower than SurVaxM's results, it's important to note that the studies had different designs and starting points for measuring survival.

Study Limitations

Both studies had limitations that are important to consider. The SurVaxM trial was relatively small and only included patients who had responded well to initial treatments, which may have skewed the results positively. The AV-GBM-1 study, while including a broader range of patients, was also small and didn't have a control group for direct comparison.

Additionally, creating personalized vaccines like AV-GBM-1 can be challenging and time-consuming, which could limit its widespread use if approved.

Discussion & Takeaways

These studies suggest that vaccine therapy could be a valuable addition to glioblastoma treatment. The ability to stimulate the immune system against cancer cells offers a new avenue of attack against this difficult-to-treat disease.

However, the researchers emphasize that larger, randomized trials are needed to confirm these promising results. They also highlight the need to better understand which patients are most likely to benefit from these vaccines and how they might be combined with other treatments for maximum effect.

The success of these early trials has led to plans for larger studies. A randomized phase 2/3 trial for AV-GBM-1 is already in the works, which will provide more definitive evidence of its effectiveness.

Funding & Disclosures

The paper notes that one of the authors, Robert O. Dillman, is employed by Aivita Biotherapeutics, the company developing AV-GBM-1. This connection is important to disclose as it could potentially influence the interpretation of the results. The other author, Daniela A. Bota, reports no conflicts of interest. The paper itself did not receive specific funding, as it is a review of existing research rather than a new study.

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