Vaccine: Angiotensin therapeutic vaccine
Manufacturer: Protherics Plc, UK
Adjuvant: CoVaccine HT™
Indication: Therapeutic vaccine for hypertension
Clinical trial: Double-blind, placebo-controlled Phase IIa
Aim: Safety and tolerability
Protherics Plc (UK) has started a double-blind, placebo-controlled Phase IIa clinical trial of its angiotensin therapeutic vaccine (ATV) for hypertension treatment. The trial is expected to involve 124 patients with mild-to-moderate hypertension, who will be given a course of injections over 6 weeks. The aim of this study is to evaluate the safety and tolerability of ATV administered with the company’s new adjuvant CoVaccine HT™.
Hypertension is a common condition that can lead to serious cardiovascular diseases, such as heart attacks and heart failure, as well as kidney damage. Individuals with hypertension current need to take blood pressure-controlling tablets every day; however, many patients fail to adhere to their medication. Therefore, a therapeutic vaccine that requires only a few injections would increase patient compliance and hence would present a preferable choice over daily tablet medication.
Protherics’ ATV contains a peptide analog of the hormone angiotensin I, which is conjugated to a carrier protein, keyhole limpet hemocyanin. The vaccine aims to induce an immune response that neutralizes angiotensin I, resulting in the control of blood pressure in hypertensive patients.
“We are excited about the prospects for ATV, a potential value driver for the company. A vaccine approach to the treatment of high blood pressure promises to address the issue of poor patient compliance with daily medication and thus reduce the incidence of stroke and heart attacks. With data expected within a year, this could be a major outlicensing opportunity,” said Andrew Heath, chief executive officer of Protherics.
In a previous Phase IIa clinical trial using Alhydrogel® as the adjuvant, ATV has been shown to modulate hormones and regulate blood pressure in hypertensive patients. In this trial, the vaccine will be adjuvanted with CoVaccine HT, a new adjuvant developed by CoVaccine BV (UK) and acquired by Protherics in 2006.
Source: Protherics Plc, UK www.protherics.com
New branch created by the NIAID to promote HIV vaccine development
A new Vaccine Discovery Branch has been created within the Vaccine Research Program in the Division of AIDS of the National Institute of Allergy and Infectious Diseases (NIAID), part of the US NIH. The aim of this new branch is to build more bridges between basic HIV researchers with vaccine designers.
“There is broad scientific consensus that designing a safe and effective vaccine to prevent HIV infection will require enormous advances beyond present-day knowledge,” said NIAID director Anthony Fauci “The NIAID Vaccine Discovery Branch will help remove fundamental obstacles to achieving this goal by focusing intensively on the development and sharing of new knowledge critical to vaccine development.”
The new branch will monitor advances in basic HIV research and vaccine design and identify knowledge gaps for future funding. “Cross-fertilization of HIV/AIDS research with the fields of genetics, structural biology, systems biology and others could open up new perspectives on how to overcome major obstacles to HIV vaccine design,” said Division of AIDS director Carl Dieffenbach. “The Vaccine Discovery Branch will be in an ideal position to spot these opportunities, promote the translation of new knowledge about HIV and foster fruitful research collaborations.”
The deputy director of the Vaccine Research Program, Jorge Flores, will serve as acting chief of the new branch until a new chief is selected.
Source: National Institute of Allergy and Infectious Diseases, US NIH, MD, USA www.niaid.nih.gov
Sinovac’s split-virion H5N1 influenza vaccine enters a Phase II clinical trial
Sinovac Biotech Ltd (China) has started to enroll volunteers for a randomized, double-blind Phase II clinical trial to evaluate the safety and immunogenicity of its split-virion pandemic influenza vaccine.
The trial will involve 210 adolescents aged between 12 and 17 years and 140 children aged between 3 and 11 years. Vaccinees will be followed up for 2 months after immunization.
“Split influenza vaccine is believed to cause less adverse reactions in children compared to whole-virion influenza vaccine. Sinovac’s split pandemic influenza vaccine aims at protecting the pediatric and adolescent population. Based on the positive safety results of the Phase I trial, the Phase II study will be conducted to further collect the vaccine’s safety data in children and adolescents, as well as assessing the immunogenicity of different doses,” said Weidong Yin, chairman, president and chief executive officer of Sinovac.
This split vaccine is the second influenza vaccine developed by Sinovac. The first vaccine, Panflu™, is a whole-virion H5N1 influenza vaccine, which was approved for production by the China State Food and Drug Administration in April 2008 and is currently the only available vaccine against H5N1 influenza in China.
Source: Sinovac Biotech Ltd, China www.sinovac.com
Promising cancer immunotherapeutic agent
ImmuFact®IMP321 as a natural human T-cell immunostimulant.
Product: ImmuFact®IMP321
Manufacturer: Immutep SA, France
Nature: Lymphocyte activation gene-3 immunoglobulin (LAG-3Ig)
Therapeutic effect: Immunopotentiator, inducing anti-tumor and antiviral CD8 T-cell responses
In an article published in the June issue of Clinical Cancer Research, a research team from Immutep SA (France) and Cell Genesys Inc. (CA, USA) has demonstrated that a novel fusion protein, lymphocyte activation gene-3 immunoglobulin (LAG-3Ig), could increase the potency of a cancer immunotherapy using GM-CSF-secreting tumor cells in a mouse model.
The LAG-3 (CD223) binds to MHC class II of antigen-presenting cells, such as dendritic cells and monocytes, and activates these cells. This, in turn, activates CD8 T cells, leading to antitumor and antiviral immune responses.
In this animal study, the tested LAG-3Ig is a murine homolog of Im-muFact® IMP321, a natural human T-cell immunostimulant. Animals receiving a combinational therapy (murine LAG-3Ig plus GM-CSF-secreting tumor cells) could survive longer than those receiving either therapy alone. These animals also had higher numbers of active CD8 T cells.
“Combination therapies are being evaluated with the goal of enhancing overall antitumor activity, which could allow treatment of patients with a large tumor burden,” said Frédéric Triebel, Immutep’s Scientific and Medical Director. “Elevated levels of TNF-α were detected in the supernatant of splenocytes isolated from animals treated with the combination therapy compared to splenocytes from animals injected with the immunotherapy alone. This increased proinflammatory cytokine production that correlated with an overall enhancement of in vivo CD8 T-cell activation clearly indicates that LAG-3 further increases antitumor activity in conditions where GM-CSF is already used as an immunostimulant.”
The immunopotentiator IMP321 can be use alone as a monotherapy, in combination with chemotherapy, or as an adjuvant in therapeutic vaccines. The product is being tested in a number of clinical trials as therapeutics for different cancers, including renal cell carcinoma, breast cancer and melanoma.
Sources: Li B, VanRoey M, Triebel F, Jooss K. Lymphocyte activation gene-3 fusion protein increases the potency of a granulocyte macrophage colony-stimulating factor-secreting tumor cell immunotherapy. Clin. Cancer Res. 14(11), 3545–3554 (2008). Immutep SA, France www.immutep.com
Progress update on the US application for the approval of Cervarix®
GlaxoSmithKline’s vaccine against cervical cancer is being reviewed by the US FDA.
Cervarix®, GlaxoSmithKline’s vaccine against cervical cancer, is currently being reviewed by the US FDA. The original application was in March 2007 and the company received FDA questions in December 2007. The company has replied to these questions and will submit further data of the Phase III pivotal efficacy study, HPV-008, which is expected to be available later in 2008. The FDA is expected to respond within 6 months after the submission of these additional data, that is, in the second half of 2009.
There are more than 500,000 newly diagnosed cases of cervical cancer with more than 280,000 deaths each year worldwide. In the USA, cervical cancer is the second leading cause of cancer death (after breast cancer) in women who were 20–39 years of age.
Cervarix has been approved in 67 countries so far, including 27 EU members, Mexico, Australia, Singapore and The Philippines. GlaxoSmithKline has also submitted licensing applications for its Cervarix in more than 35 additional countries.
“Study 008 is a key study that will be completing later this year, and we expect the final results will strengthen the US label for Cervarix,” said Barbara Howe, Vice President and Director, North American Vaccine Development, GlaxoSmithKline. “We continue to have positive and productive discussions with the FDA and remain confident in the vaccine’s safety and efficacy profile. We look forward to bringing this important new cervical cancer vaccine to girls and women in the USA.”
Source: GlaxoSmithKline www.gsk.com
New high-tech vaccine-production site in France
A new high-tech vaccine-production facility has been opened in Val de Reuil, northwest of France, by Sanofi Pasteur, the vaccines division of the Sanofi Aventis Group. This highly automated unit is designed to produce 200 million syringes and vials each year, which is twofold of the current capacity at this site. The new 7800-m2 facility cost €100 million to build and is part of the €600-million investment that Sanofi Pasteur undertakes in France between 2005 and 2008.
“Sanofi Pasteur’s commitment to global health is exemplified by significant investments in vaccine-production infrastructures. These efforts are aimed at meeting a world demand for vaccines expected to double by 2016,” said Wayne Pisano, president and chief executive officer of Sanofi Pasteur, who inaugurated the new production unit. “The new facility will provide high-end production work environment for dedicated people who pr-oduce vaccines for the world.”
The new facility is expected to start operating by the end of 2008 and can then produce vaccines against 20 diseases. It is also suitable for the production of pandemic influenza vaccines should a pandemic occur.
“Sanofi Pasteur Val de Reuil site is a hub for global health with over 2 million doses of vaccines shipped worldwide each day. The new facility will further enable Sanofi Pasteur to fulfill its commitment of providing highest quality vaccines to protect people from infectious diseases wherever they live,” added Pisano.
Source: Sanofi Pasteur www.sanofipasteur.com