T-Vec immunotherapy approved for advanced skin cancer
The FDA has approved talimogene laherparepvec (T-Vec, Amgen) immunotherapy as a second-line treatment for inoperable melanoma. T-Vec is an engineered herpes virus injected into the tumor, where it replicates to kill cancer cells and elicit an immune response. Distributed under the trade name Imlygic, it is the first oncolytic therapy approved in the U.S.
The application was supported by data from the Phase 3 OPTiM trial showing that T-Vec shrank tumors at a significant rate. The immunotherapy also is being tested in combination with PD-1 inhibitors in advanced melanoma, head-and-neck, colon and breast cancers.
Repeated Tdap vaccination in pregnancy is safe
Maternal immunization with a booster tetanus, diphtheria, and acellular pertussis (Tdap) vaccine was not associated with increased adverse events in women who received a tetanus-containing vaccine up to 5 years previously.
A study published in The Journal of American Medical Association1 monitored almost 30,000 pregnant women from 6 U.S. states during 2007-13, and found no increase in adverse events, such as fever and allergy, or adverse birth outcomes, such as preterm delivery and low birth weight of the newborns, compared to a control group vaccinated >5 years previously.
The U.S. Advisory Committee on Immunization Practices recommends Tdap vaccination in pregnancy regardless of prior immunization status. This is the first safety report on repeated vaccination.
1. Sukumaran L, McCarthy NL, Kharbanda EO, McNeil MM, Naleway AL, Klein NP, Jackson ML, Hambidge SJ, Lugg MM, Li R, Weintraub ES, Bednarczyk RA, King JP, DeStefano F, Orenstein WA, Omer SB. Association of Tdap Vaccination With Acute Events and Adverse Birth Outcomes Among Pregnant Women With Prior Tetanus-Containing Immunizations. JAMA 2015; 314(15):1581-1587.
Pembrolizumab approved by FDA for treatment of NSCLC
Anti-PD-1 monoclonal antibody (MAb) pembrolizumab (Keytruda, Merck) was approved by the U.S. Food and Drug Administration (FDA) for treatment of advanced non-small cell lung cancer (NSCLC). This immunotherapeutic MAb inhibits the PD-1 pathway that some tumors use to escape the immune system. The approval applies to patients with high expression levels of the target protein PD-L1.
Data on pembrolizumab's clinical benefits were released shortly after approval. In a Phase 2/3 study involving >1,000 patients, the MAb was superior to standard-of-care chemotherapy docetaxel in overall survival, but not in progression-free survival for the whole population. Only patients with high PD-L1 levels lived longer without tumor progression.
Pembrolizumab, similarly to another anti-PD-1 MAb nivolumab (Opdivo, BMS), is also approved for treatment of advanced melanoma.
New influenza vaccine-production technology might increase the yield by up to 10-fold
The combination of high-virulence influenza virus mutants and mammalian cell-based vaccine production could provide 2- to 10-fold the yield of traditional egg-based production. A study published in Nature Communications1 identified gain-of-function mutations in influenza A virus that made it more efficient at replicating in mammalian cells, and used the strains for vaccine production in a mammalian cell line.
The study was conducted before the 2014 moratorium, which the U.S. National Institutes of Health placed on gain-of-function research involving influenza, SARS and MERS viruses to allow for adoption of regulatory policies.
Most influenza vaccines are manufactured by growing the virus in fertilized chicken eggs, deactivating and purifying it. “Existing strains of flu vaccine virus don't grow well in cells and there is only one company in the United States currently using cell-based production methods,” senior author Yoshihiro Kawaoka of University of Wisconsin and University of Tokyo explained. “But there is a trend toward cell-based production, and we think this work can contribute to that.”
1. Ping J, Lopes TJ, Nidom CA, Ghedin E, Macken CA, Fitch A, Imai M, Maher EA, Neumann G, Kawaoka Y. Development of high-yield influenza A virus vaccine viruses. Nat Commun 2015; 6:8148
FDA grants priority review for daratumumab in refractory multiple myeloma patients
The anti-CD38 MAb daratumumab (Janssen Biotech) was assigned priority review by the U.S. FDA for treatment of refractory multiple myeloma (MM). Final decision is scheduled for March 2016.
Daratumumab was successful in a Phase 2 SIRIUS study, in which patients who failed prior treatment showed 65% one-year survival and 30% objective response rate with 12% complete or very good partial responses. Daratumumab is being evaluated in several Phase 3 trials that investigate various treatment settings for MM patients.
HPV vaccination might be discouraged by lukewarm attitudes of many U.S physicians
U.S. physicians communicate with patients and parents about HPV vaccination in ways that are likely to be discouraging, according to a report published in Cancer Epidemiology, Biomarkers & Prevention.1 The authors conducted an online survey among U.S. pediatricians and family physicians, in which they measured five factors of HPV recommendation, such as timeliness and urgency.
“We were surprised that physicians so often reported recommending HPV vaccination inconsistently, behind schedule, or without urgency. Of the five communication practices we assessed, about half of physicians reported two or more practices that likely discourage timely HPV vaccination,” corresponding author Melissa Gilkey of Harvard Medical School said in a statement.
Despite the excellent safety and efficacy record of HPV vaccines, 27% of physicians reported that they did not strongly endorse HPV vaccination, while 26% and 39% indicated that they did not provide timely recommendations for immunizing girls and boys, respectively. Yet, healthcare provider's attitude is probably the single most important factor in parental decision-making, according to previous studies. “Our findings suggest that physicians can improve their recommendations in three ways: by recommending HPV vaccination for all 11- to 12-year-olds and not just those who appear to be at risk; by saying the HPV vaccine is very important; and by suggesting vaccination on the day of the visit rather than at a later date,” Gilkey concluded.
1. Gilkey MB, Malo TL, Shah PD, Hall ME, Brewer NT. Quality of Physician Communication about Human Papillomavirus Vaccine: Findings from a National Survey. Cancer Epidemiol Biomarkers Prev 2015; doi: 10.1158/1055-9965.EPI-15-0326
Immunotherapy for HER2-expressing solid tumors entered clinical trials
ADXS-HER2 immunotherapy (Advaxis) has started a dose-escalation Phase 1b trial in patients with tumors expressing epidermal growth factor receptor 2 (HER2). The study enrolling ~18 subjects with metastatic breast, gastric, esophageal or bone cancers will determine the safety and maximum tolerated dose of ADXS-HER2.
HER2 is overexpressed in a number of solid tumors. It is associated with more aggressive disease, high rate of relapse, and low survival.
ADXS-HER2 is based on an engineered live attenuated Listeria monocytogenes strain that was able to generate T-cell responses as well as inhibit regulatory T cells in preclinical studies. The same technology is being developed for treatment of cervical cancer (Axalimogene Filolisbac), but this investigation was placed on hold after treatment-related death of one patient.
Two meningitis and Tdap vaccines induce comparable immune responses when administered together
Co-administration of a meningococcal serogroup B vaccine Trumenba (Pfizer) and two other approved vaccines Menactra and Adacel (both Sanofi Pasteur) did not decrease their immunogenicity. In a randomized Phase 2 study involving >2,600 healthy subjects aged 10–12 years, immune responses were comparable between cohorts receiving Trumenba alone, Menactra and Adacel alone, and all three vaccines together.
Menactra protects against meningococcal serogroups A, C, Y and W, and Adacel is a Tdap vaccine. Co-administration could be a significant step towards greater uptake and adherence to recommended immunization schedules. Trumenba and Menactra together cover the five strains responsible for most cases of invasive meningococcal disease worldwide. In 2014, U.S. universities saw an increased incidence of meningococcal serogroup B, which led to accelerated approval of Trumenba by the FDA.
WHO recommends using bivalent polio vaccine from April 2016
The World Health Organization (WHO) panel recommended excluding type 2 polio from trivalent vaccine. It should be replaced by a bivalent oral vaccine in April 2016. The type 2 polio virus has not been detected since 1999, yet it is estimated to be responsible for 90% of vaccine-induced disease after replicating in the gut and transmitting to unvaccinated children through contaminated water.
WHO also recommended gradual replacement of oral vaccine by the injectable inactivated polio vaccine. “We think it's realistic that we will get polio eradicated in the next few years,” panel chair Jon Abramson told the media.
GEN-004 pneumococcal vaccine development stopped after clinical trial failure
The development of a novel pneumococcal vaccine GEN-004 (Genocea) has been suspended after a Phase 2 trial failed to meet its primary endpoints. The randomized, double-blind study involved 100 individuals who received 3 intranasal doses in 4-week intervals. GEN-004, which contains three conserved pneumococcal protein antigens associated with a Th17 T-cell response, did not achieve significantly better protection than placebo.
An estimated 1.6 million people, half of them children, die each year of pneumococcal infection, according to WHO. The pathogen also causes non-invasive infections of respiratory tract, such as otitis media and pneumonia.
An HIV vaccine candidate enters clinical trials
University of Maryland has started recruiting volunteers for a Phase 1 study of an HIV vaccine, Full Length Single Chain. The vaccine is designed to elicit broad immune response to numerous HIV strains, which is what past efforts to develop an efficacious vaccines have failed to do.
There are several other HIV vaccines ready to enter clinical trials, including candidates from the Scripps Research Institute, Harvard University and J&J.