Abstract
High safety marks for Merck’s Gardasil
Cuba tests prostate cancer vaccine
HIV’s weak spot: V2
Unique anti-cancer agent ColoAd1 enters the clinic
Broadly neutralizing antibodies against influenza A and B discovered
Clinical trials initiated: Nexvax2 therapeutic vaccine for celiac disease
The 20 top-selling vaccines in the first half of 2012
Influenza vaccine safe for pregnant women
High safety marks for Merck’s Gardasil
High safety marks were given to Merck’s human papilloma virus (HPV) vaccine Gardasil. A new study published in the journal Archives of Pediatrics and Adolescent Medicine1 looked at side effects of this vaccine in a large number of female and did not detect evidence of new safety concerns among females 9 to 26 y of age following vaccination with Gardasil.
In this US government-required study, 190,000 females in Kaiser Permanente’s California insurance system were followed for 60 d after receiving Gardasil. The only short-term side effects associated with the vaccine were fainting and infection. Study results showed that patients were six times more likely to have fainted the day of the shot than in the following weeks and 1.8 times more likely to report a skin and subcutaneous tissue infection in the two weeks after. However, no serious adverse effects occurred, and no link to more serious health problems was reported.
Study lead author Dr. Nicola Klein, co-director of the Kaiser Permanente Vaccine Study Center in Oakland told NJ.com, “The take-home message is this is a very reassuring finding. Patients and providers should be aware to follow the Centers for Disease Control and Prevention guidelines for 15 minutes after this vaccine.”
Two HPV vaccines are currently licensed in the USA, Gardasil and Cervarix (GSK). On the list of the top-selling vaccines this year, Gardasil is placed 3rd, while Cervarix falls into 8th place.
Reference
1. Klein NP, et al. Arch Pediatr Adolesc Med 2012; 1:1-9; PMID: 23027469; 10.1001/archpediatrics.2012.1451.
Cuba tests prostate cancer vaccine
Recently, Phase 2 clinical trials for the potential prostate cancer vaccine Heber Provac have been completed in Cuba, and results are being processed. The vaccine, developed by the Center for Genetic Engineering and Biotechnology (CIGB) in Camaguey, a city 530 km east of Havana, was tested in 56 patients with advanced prostate cancer. Heber Provac was applied before patients received X-ray or chemotherapy treatment, in order to make hormonal suppression possible.
According to urologist Dr Ranfis Rodriguez, who led the research at Camaguey, the study analysis will focus on the decrease in the tumor marker values or prostate specific antigen, prostate reduction, and little or no testosterone production. While not all men included in the sample have been examined yet, Rodriguez said that so far they have seen compliance of these parameters, along with marked improvement in the quality of life of patients.
Dr Jesus Junco, in charge of the project by the CIGB, said that this therapeutic vaccine designed to combat stage 3 and 4 malignant tumors should be able to match or outperform standard treatments, which are expensive for Cuba to acquire in the international market.
Once evaluations of the phase 2 study have been completed, the next trial Phase will start, including more patients, testing Heber Provac’s interactions with other drugs and comparing it with standard therapy. According to official data, each year 2,500 men—most of them over 60 y of age—develop prostate cancer in Cuba. Sixty percent of the cases eventually are fatal.
HIV’s weak spot: V2
Researchers have identified a weak spot of human immunodeficiency virus (HIV), which may bring an effective vaccine against AIDS closer to reality. A new study published recently in the journal Nature1 sheds light on how a vaccine can turn the immune system against the invading HIV and so offer protection from infection.
Three years ago, results from the RV144 vaccine trial showed a reduction in HIV infections; however, the response rate of 31% was unexpectedly low. Subsequent analysis of the RV144 data revealed that those who responded to the vaccine and fended off HIV tended to produce antibodies against the V1/V2 loop, a specific part of the virus’s protein shell. These data were published earlier this year in the New England Journal of Medicine.2
The new Nature study goes one step further, showing that vaccinated subjects who still contracted HIV had been infected by viruses that had mutations in the V2 portion. A research team led by Drs Morgane Rolland and Jerome Kim at the US Military HIV Research Program in Silver Spring MD (USA) examined 936 sequences collected from 44 trial participants who received the vaccine and became infected, and 66 subjects who received the placebo. Two mutations were identified that seemed to be linked to vaccination success. Both were located in the V2 region of the V1/V2 loop. The team compared the rates of infection with viruses whose sequence varied at these two sites between people who received the vaccine and those with placebo. People who received the vaccine were 80% less likely than placebo recipients to be infected by viruses with these mutations. The study data suggest that the vaccine triggered an immune response that prevented certain viruses from infecting them, and only viruses with different sequences at these two sites had a good chance of creating an infection.
“This is a really good paper,” said Dr Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, Maryland. “It adds to the growing body of information indicating that an immune response against components of the V1/V2 loop is important in vaccine-induced protection against infection.”
Vaccine developers have become interested in ways to improve the response against V2. Trials for a vaccine similar to that used in RV144 are planned for 2014 in South Africa and among homosexual men in Thailand. Dr Jerome Kim helps to design these trials and hopes that a booster within a year of the first immunization and a new adjuvant will elicit a stronger and longer-lasting immune response against HIV and its V2 region.
References
1. Rolland M, et al. Nature 2012; 490:417-20; PMID: 22960785; 10.1038/nature11519
2. Haynes BF, et al. N Engl J Med 2012; 366:1275-86; PMID: 22475592; 10.1056/NEJMoa1113425
Unique anti-cancer agent ColoAd1 enters the clinic
The UK-based development stage biotechnology company PsiOxus Therapeutics has recently announced the start of a phase 1/ 2 clinical trial of the oncolytic vaccine ColoAd1 for the treatment of metastatic solid tumors.
The multinational phase 1/ 2 study (Evolve study) will be conducted at up to 20 sites in Europe. Regulatory approvals to proceed with the study have so far been received for the UK, Spain and Belgium, where the first patient was dosed in September. Safety, biological activity and efficacy of ColoAd1 will be evaluated in 126 patients, with initial results expected by the end of 2013. The phase 1 stage is recruiting patients with solid tumors, who have no further conventional treatment options open to them. The aim of this initial phase is to establish a safe dose schedule for ColoAd1 in cancer patients. The phase 2 component will then recruit patients with metastatic colorectal cancer and who have already received standard first-line therapy. Primary endpoint of the phase 2 component is Progression Free Survival (PFS) when compared with patients receiving standard therapy alone. Secondary endpoints include response rates and overall survival.
Dr John Beadle, CEO of PsiOxus, commented, “The Evolve study is a major milestone for both PsiOxus and ColoAd1 as we test a new form of anti-cancer agent with greatly improved selectivity for tumor cells in humans for the first time. While there remains much work to be done, the Evolve study could forge a path to a new treatment option for patients with metastatic cancer. The advantage of this type of cancer vaccine is that the immune response will be specific for each patient’s own personal cancer.”
The highly potent, broad-spectrum, anti-cancer therapeutic is capable of destroying tumor cells at minute concentrations. After injection into the bloodstream, the vaccine components reach the cancer sites, where they replicate inside of cancer cells to trigger cell death. Each infected cell produces thousands of new copies of ColoAd1, which spread to nearby cancer cells and kill them as well, while ignoring normal cells. The approach represents a new generation of so-called “self-amplifying” cancer therapy that has the effect of killing tumors and acting as a cancer vaccine.
ColoAd1is highly effective at selectively targeting and killing cancer cells. It has been shown to be up to 1,200 times more potent at killing human cancer cells than non-cancerous human cells. This is a clear advantage over standard chemotherapy agents, which are much less selective for cancer cells and account for the often severe side effects of chemotherapy. Furthermore, scientists in Professor Len Seymour’s lab at the University of Oxford, UK have shown that ColoAd1 survives very well in human blood.
“This characteristic is fairly unique to ColoAd1 and is not shared with many other viruses. This means that ColoAd1 can be delivered efficiently by intravenous infusion, which is a significant advantage over many other oncolytic viruses in development. The bloodstream will carry the ColoAd1 to all metastatic cancer sites in the body, where they can self-amplify at the site of action, making this a very exciting step forward in the field,” explains Dr. Seymour.
Broadly neutralizing antibodies against influenza A and B discovered
A new study raises hopes for the development of monoclonal antibody (mAb)-based immunotherapy and universal vaccines for influenza. Scientists at The Scripps Research Institute and Crucell Vaccine Institute identified new antibodies that neutralize and block both strains—A and B—of the seasonal influenza virus.
“To develop a truly universal flu vaccine or therapy, one needs to be able to provide protection against influenza A and influenza B viruses, and with this report we now have broadly neutralizing antibodies against both,” said Dr Ian Wilson, the Hansen Professor of Structural Biology at Scripps Research and senior investigator for the new study.
The dual-strain nature of the seasonal flu represents a particularly daunting task for vaccine makers. While most deadly strains of influenza are A strains, the B strain of the virus is the more common variety. A substantial part of the annual flu burden is caused by two cocirculating antigenically distinct lineages of influenza B viruses. Broadly neutralizing antibodies had previously been identified against influenza A viruses. For the new study, antibodies were collected from bone marrow volunteers who took a flu vaccine or were infected with multiple strains of the virus. The resulting library, which contained billions of antibodies, was screened against a variety of B strains. The researchers identified three human mABs that protected mice against lethal challenge from both strain B lineages. While two of the mABs (CR8033 and CR8071) recognize distinct conserved epitopes in the head region of the influenza B hemagglutinin (HA), the third mAb (CR9114) binds a conserved epitope in the HA stem and protects against both strains of influenza virus—A and B—simultaneously, making it the most promising one. The study results were published in the journal Science.1
The identified antibodies could be used to develop a vaccine and treatment for severe infections, or to help protect hospital staff. Ultimately, a vaccine that does not need to be given seasonally could result from the study findings. “Clearly, the ‘Holy Grail’ is a universal flu vaccine, and this is another important step toward that,” said Dr Wilson.
Reference
1. Dreyfus C, et al. Science 2012; 337:1343-8; PMID: 22878502; 10.1126/science.1222908
Clinical trials initiated: Nexvax2 therapeutic vaccine for celiac disease
The biotech company ImmunsanT recently announced the initiation of clinical trials in New Zealand, Australia and the USA to evaluate Nexvax2, the first therapeutic vaccine for patients with celiac disease.
This inherited autoimmune disorder affects the digestive process of the small intestine. When a person with celiac disease consumes gluten, a protein found in wheat, rye and barley, the individual’s immune system responds by triggering T cells to fight the offending proteins, damaging the small intestine and inhibiting the absorption of important nutrients into the body. Currently no drug therapy is available. Thus, the only option for people with celiac disease is to eliminate gluten from the diet. Compliance is often challenging, and nearly half the people on the strict elimination diet still have residual damage to their small intestine. Undiagnosed, celiac disease is a major contributor to poor educational performance and failure to thrive in children. In adults, untreated disease is associated with increased risk of fractures and osteoporosis, problems during pregnancy and birth, short stature, dental enamel hypoplasia, dermatitis, recurrent stomatitis and cancer.
The therapeutic vaccine Nexvax2 combines three proprietary peptides that elicit an immune response in patients with celiac disease who carry the immune recognition gene HLA-DQ2. Similar to treatments for allergies, the vaccine is designed to reprogram gluten-specific T cells triggered by the patient’s immune response to the protein. The goal is for Nexvax2 to restore celiac patients’ immune tolerance to gluten, reduce inflammation in the nutrient-absorbing villi that line the small intestine, return the intestine to a healthy state, and allow patients to eat a normal diet.
The new clinical program in Australia and New Zealand is a randomized, double-blind, placebo-controlled phase 1b study, which evaluates multiple ascending doses of Nexvax2 for the induction of gluten tolerance in patients on a gluten-free diet. Safety, tolerability and pharmacokinetics will be studied in 84 subjects at four sites in these two countries.
The US study will enroll 30 adult subjects with celiac disease, well controlled by a gluten-free diet. This randomized, double-blind, placebo-controlled phase 1 trial is to determine the safety, tolerability and pharmacokinetic profile of Nexvax2.
Patients participating in these international trials will have a confirmed diagnosis of celiac disease and carry the immune recognition gene HLA-DQ2 (up to 90% of individuals with celiac disease have this gene). The vaccine will be delivered using the latest intradermal injection technology provided by BD (Becton, Dickinson and Company).
“We are kicking-off a robust clinical program that we hope demonstrates Nexvax2 dramatically reduces the body’s immune response to dietary gluten so patients can resume a normal diet and return to good health,” said Dr Patrick Griffin, Chief Medical Officer of ImmusanT. “Our clinical development program will allow us to further examine the role of antigen-specific T cells in celiac disease activation and in the re-establishment of tolerance to gluten.”
“There has been tremendous enthusiasm about Nexvax2 from patients and the medical community and this will provide terrific momentum for advancing our clinical program,” added Dr Leslie Williams, President and CEO of ImmusanT.
The 20 top-selling vaccines in the first half of 2012
As the first half (H1) of 2012 came to a close, Fierce Vaccines took a look at which prophylactic vaccines were sold most often, and which companies made the sales. The data provided by Fierce Vaccines help to understand what is driving growth in the vaccines industry and which companies are dominating the field.
Over the past 10 y the vaccine market has grown from $5.7 billion to $27 billion, according to Kalorama Information. This increase in revenue is in part due to the recent focus on influenza prevention, acceptance of adult vaccines, as well as the introduction of new vaccines such Gardasil and Prevnar.
Not surprisingly, the list of the 20 top-selling vaccines (below) is dominated by Big Pharma. Merck and GlaxoSmithKline (GSK) had 6 vaccines each in the top 20 sales. Pfizer and Sanofi also had multiple products on the list, and Novartis and Emergent BioSolutions had one product each. More information on sales numbers can be found here: http://www.fiercevaccines.com/special-report/20-top-selling-vaccines/2012-09-25#topvaccines
(1) Prevnar 13 (Pneumococcal infection); Pfizer
(2) PENTAct-HIB (Diphteria, Haemophilus Pertussis/whooping cough, Tetanus, Polio, Hemophilus influenza type b); Sanofi
(3) Gardasil (HPV); Merck
(4) Pediarix (Diphtheria, Tetanus, Pertussis/whooping cough, Hepatitis B, Polio); GSK
(5) Hepatitis Vaccine Franchise (Hepatitis A, Hepatitis B); GSK
(6) Celtura (Swine Flu); Novartis
(7) Varivax (Varicella virus); Merck
(8) Cervarix (HPV); GSK
(9) RotaTeq (Rotaviral gastroenteritis); Merck
(10) Synflorix (Pneumococcal infection, Otitis media); GSK
(11) Rotarix (Rotaviral gastroenteritis); GSK
(12) Zostavax (Shingles, Herpes); Merck
(13) Prevnar (Pneumococcal infection, Otitis media); Pfizer
(14) Fluzone/Vaxigrip (Influenza); Sanofi
(15) Menactra (Meningitis); Sanofi
(16) Pneumovax (Pneumococcal infection); Merck
(17) Adacel (Diphtheria, Pertussis/whooping cough, Tetanus); Sanofi
(18) MMR-II (Measles, Mumps, Rubella); Merck
(19) Boostrix (Diphtheria, Tetanus, Pertussis/whooping cough); GSK
(20) Biothrax (Anthrax); Emergent BioSolutions
Influenza vaccine safe for pregnant women
Results of a new study suggest that influenza vaccination is safe for pregnant women, even in the first trimester. The study, recently published in the journal Obstetrics and Gynecology (www.ncbi.nlm.nih.gov/pubmed/22914461), set out to estimate the effect of first-trimester influenza vaccination on fetal and neonatal outcomes and included almost 9,000 pregnant women who received the vaccine. Results from the study showed that influenza vaccination in the first trimester was not associated with an increase in major malformation rates, but was associated with a decrease in the overall stillbirth rate. This information may aid in counseling women regarding the safety of influenza vaccination during pregnancy.
“The flu is a problem in pregnancy,” said study lead author Dr. Jeanne Sheffield, a professor of obstetrics and gynecology at the University of Texas, Southwestern Medical Center in Dallas. “But we have a vaccine to prevent it. And it is considered safe and effective in any trimester.”
Pregnant women are more likely than other women their age to get a severe case of the flu or have complications. Therefore, doctors do recommend that pregnant women receive a flu vaccine, but most women in the USA do not. According to Reuters, only 10–25% of women have been vaccinated each flu season over the past couple of decades.