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Two PD-1 inhibitors were successful in non-small cell lung cancer (NSCLC) patients. In a Phase 2 trial involving nearly 300 people, MPDL3280A (Roche) doubled survival prospects of patients with high PD-L1 levels, when compared to chemotherapy. The benefit for patients with low PD-L1 levels was less pronounced. Mixed results were reported from a Phase 3 study of almost 600 patients with non-squamous NSCLC. Opdivo (BMS) showed up to 60% increase in survival compared to chemotherapy in high-PD-L1 subjects but failed in PD-L1-negative patients. Opdivo had been approved by FDA for squamous NSCLC.
Opdivo has been tested in two more trials. In 47 evaluable patients with advanced liver cancer, it showed a 1-year survival rate of 62%, with 19% having complete response. Additionally, a Phase 3 study of nearly 1,000 patients with previously untreated advanced melanoma showed greatest benefit of Opdivo together with another checkpoint inhibitor, anti-CTLA-4 Yervoy (BMS). This combination therapy reduced the risk of disease progression by 60% compared to Yervoy alone. However, it also more than doubled the rate of serious adverse events, such as colitis and lung inflammation.
Finally, another PD-1 inhibitor Keytruda (Merck) posted promising results in a Phase 1 trial involving 130 patients with recurrent or advanced head and neck cancer. More than half of the subjects had a partial response, and one quarter showed tumor shrinkage by ≥30%. The treatment was well tolerated with few side effects.
GEN-003 vaccine (Genocea) against genital herpes helped patients combat the chronic herpes simplex virus (HSV) infection in a Phase 2 trial. A cohort of >300 patients were divided into 7 groups and subjected to placebo or escalating doses of GEN-003 plus adjuvant Matrix-M2. The most efficacious vaccine formulation inhibited viral shedding by more than half over the 4-week study period.
The candidate therapeutic vaccine contains HSV-2 viral antigens ICP4 and gD2. It is designed to elicit T-cell response.
It is estimated that one of every 6 people aged 14–49 has genital herpes in the U.S. alone. The virus is latent in nervous tissue and migrates to the skin to shed, i.e., release HSV.
Celldex' Rintega prolonged survival of brain cancer patients in a Phase 2 ReACT study. In a cohort treated with Rintega together with Avastin (Roche), survival after one year was 45% and the median overall survival rate was 11.6 months, compared with 31% and 9.3 months in Avastin-only control group.
Rintega is a therapeutic vaccine targeting EGFRvIII, which is permanently activated in glioblastomas with the worst prognosis. Avastin is a monoclonal antibody against VEGF-A and is a standard of care in brain tumor patients.
“The results of the ReACT study are striking because we are observing an extremely rare overall survival advantage that is now translating into long-term survival for a number of patients—something not seen in highly aggressive, EGFRvIII-positive glioblastoma,” said lead investigator David Reardon in a press release. “Importantly, patients on the Rintega arm are not only surviving longer, they are experiencing a notable decrease in the need for steroids and the numerous side effects associated with their use.”
Rintega received a breakthrough designation by the FDA. Phase 3 data are expected later this year.
The combined DTaP-polio vaccine Quadracel (Sanofi) has been approved by the U.S. Food and Drug Administration. The vaccine combines the 5th dose in the DTaP series and 4th or 5th dose in the polio series in children aged 4–6 years, thus reducing the total number of injections a child has to endure. Quadracel is on the market in Canada and Australia.
The approval is based on Phase 3 data comparing Quadracel with separately administered DTaP and polio vaccines. The results showed similar safety and immunogenicity profiles.
Sanofi is also working on a hexavalent DTaP-polio-Hib-hepatitis B vaccine, for which an application was approved by FDA in 2014.
Up to 86% response rate was observed in a Phase 1 dose-escalation study of GEN-1 therapy (Celsion) against platinum-resistant ovarian cancer. 16 patients were treated with GEN1 together with pegylated doxorubicin and evaluated for safety and efficacy.
The results showed an overall clinical benefit of 57% across all cohorts with a partial response rate of 21%. GEN-1 was well tolerated, and the maximum tolerated dose was not reached.
“These clinical results are very encouraging, especially given the fact that patients suffering from advanced relapsed ovarian cancer have typically failed previous treatments and have limited treatment options for this aggressive cancer,” senior investigator Premal Thaker said in a statement.
GEN-1 is a DNA therapy, in which an IL-12-expressing vector formulated in a nanoparticle delivery system is injected intraperitoneally into the tumor. IL-12, one of the most active cytokines, stimulates T cells and NK cells to proliferate and combat cancer cells.
A patient is more likely to start and complete HPV vaccine series if the provider has set up electronic alerts, as published in Journal of American Board of Family Medicine.1 The researchers monitored health record systems of 6,000 providers with and 9,000 without reminders. In the former set, patients aged 9–18 were 3 times more likely to start the HPV vaccine series and 10 times more likely to finish it. The figures were 6 and 8 times more likely in patients aged 19–26.
The HPV vaccine has the lowest completion rates of ˜1/3. “Our findings suggest that these prompts through the electronic health system may be a valuable tool in encouraging more people to protect themselves from cancer,” lead author Mack Ruffin said in a press release. “We're a long way away from achieving the HPV vaccination rates we'd like to see, but our findings potentially identify another valuable step in helping us get closer to our goal.”
1. Ruffin MT th, Plegue MA, Rockwell PG, Young AP, Patel DA, Yeazel MW. Impact of an Electronic Health Record (EHR) Reminder on Human Papillomavirus (HPV) Vaccine Initiation and Timely Completion. J Am Board Fam Med 2015; doi: 10.3122/jabfm.2015.03.140082
Haemophilus influenzae type b (Hib) vaccine can prevent acute lymphoblastic leukemia (ALL), the most common tye of childhood cacer, and researchers have identified the mechanism. According to a study published in Nature Immunology,1 chronic Hib infection hyperactivates AID and RAG immunological pathways, normally responsible for diversifying immunoglobulin-encoding genes in developing B lymphocytes, thereby causing genetic lesions and oncogenesis.
“These experiments help explain why the incidence of leukemia has been dramatically reduced since the advent of regular vaccinations during infancy,” senior author Markus Müschen said in a statement.
ALL accounts for a quarter of cancer diagnoses in children aged <15 years. The researchers now examine whether ALL can be caused by viral infections as well.
1. Swaminathan S, Klemm L, Park E, Papaemmanuil E, Ford A, Kweon SM, Trageser D, Hasselfeld B, Henke N, Mooster J, Geng H, Schwarz K, Kogan SC, Casellas R, Schatz DG, Lieber MR, Greaves MF, Müschen M. Mechanisms of clonal evolution in childhood acute lymphoblastic leukemia. Nat Immunol 2015; doi: 10.1038/ni.3160
The smallpox vaccine Imvamune (Bavarian Nordic) has passed large-scale trials in two different formulations. The liquid-frozen vaccine was administered to 3,000 vaccinia-naïve individuals in 3 different lots (1,000 per lot + 1,000 placebo group) in a Phase 3 study. No serious adverse events were reported with immunogenicity meeting the primary endpoints.
In addition, the freeze-dried Imvamune was compared to the liquid-frozen formulation in a Phase 2 trial involving 650 healthy subjects. The safety and immunogenicity profiles were comparable between the two cohorts.
The freeze-dried version of Imvamune, which is advantageous for biodefense stockpiling, should be ready for delivery in 2016.
>600,000 Liberian children will be vaccinated against polio and measles in the near future. The joint plan of World Health Organization, U.S. Centers for Disease Control and Prevention, UN Children's Fund, and the Ministry of Health and Social Welfare in Liberia aims to reinstate health care after a setback caused by recent Ebola epidemic.
Almost 700,000 children aged up to 59 months will receive the polio vaccine, and 600,000 children 6–59 months old will be vaccinated against measles. The campaign was originally scheduled for 2014, but routine vaccination was not administered during the Ebola epidemic due to limited resources.
A vaccine against angiotensin II decreased blood pressure in a preclinical study published in the journal Hypertension.1 The DNA vaccine was administered to hypertensive rats through a needleless injection three times every two weeks. Over the study period of 6 months, the rats showed decreased blood pressure and lower damage to the heart and blood vessel tissue. No damage to liver or kidneys was reported.
Angiotensin II is a hormone responsible for blood vessel constriction, which leads to elevated blood pressure and increased heart activity.
“The potential of a vaccine for hypertension offers an innovative treatment that could be very effective for the control of non-compliance which is one of the major problems in the management of hypertensive patients,” co-senior author Hironori Nakagami of Osaka University said in a press release. “Further research on this DNA vaccine platform, including increasing the longevity of blood pressure reduction, may eventually provide a new therapeutic option to treat hypertensive patients.”
1. Koriyama H, Nakagami H, Nakagami F, Osako MK, Kyutoku M, Shimamura M, Kurinami H, Katsuya T, Rakugi H, Morishita R. Long-Term Reduction of High Blood Pressure by Angiotensin II DNA Vaccine in Spontaneously Hypertensive Rats. Hypertension 2015; doi: 10.1161/HYPERTENSIONAHA.114.04534
ProBioGen's Ebola vaccine candidate entered clinical trials. It is a modified vaccinia Ankara (MVA) Ebola Zaire vaccine expressed in the proprietary Muscovy duck AGE1.CR.pIX cell line. The Phase 1 trial is underway at Jenner Institute of Oxford University in the U.K.
The manufacturing platform independent of embryonated chicken eggs allows large-scale production and flexibility. “Production of the first-ever batch of MVA for a clinical trial using a cell line is a milestone in the development of this important vaccine technology,” Adrian Hill of Jenner Institute said in a statement. “This new process, which will allow very large scale production, will be of value not only for Ebola prevention, but also for a wide range of other disease indications including malaria and tuberculosis vaccination.”