Clinical Program Update - Vaccines
Influenza - Seasonal Flu Vaccine (FluCell collaboration with sanofi pasteur): Based on Phase I clinical study results of the seasonal influenza vaccine developed by Crucell's partner sanofi pasteur, using PER.C6Â® technology, Phase II testing of the cell culture-based seasonal influenza vaccine was initiated in the U.S. This project is part of a contract awarded in 2005 by the U.S. Department of Health and Human Services (HHS) aimed at accelerating the development of a new cell culture-based influenza vaccine. Phase II trials involving healthy adult volunteers in the U.S. will focus further on the safety profile and immunogenicity of the cell-based vaccine.
This vaccine was developed using Crucell's PER.C6Â® technology, which offers sanofi pasteur a promising and reliable production method for seasonal and pandemic influenza vaccines in addition to traditional, proven egg-based production. The production scale potential of the PER.C6Â® cell line has been demonstrated in a bioreactor of 20,000 liters, suggesting robustness of PER.C6Â® technology.
Influenza - Pandemic Flu Vaccine H9N2:Â Phase I and II studies have been completed and the results are currently being analyzed. No serious adverse side effects were reported to date. Findings are expected to be released first half of 2008.
- Hepatitis A: Pediatric EpaxalÂ® was licensed early 2007 in Switzerland. The product is currently under registration in selected endemic countries.
Whole-killed West Nile Virus Vaccine: The Phase I trial for a vaccine was completed, demonstrating safety and tolerability. Crucell also developed human monoclonal antibodies for therapeutic use against West Nile. It has been decided that these programs will no longer be continued. Crucell has come to the conclusion that the commercial and market opportunities for its West Nile products are not as attractive as other products in Crucell's pipeline.
- Live Attenuated Yellow Fever Vaccine FlavimunÂ®: Given the successful sales of the MoRuViratenÂ® vaccine for Measles/Rubella, which is produced in the same facility as FlavimunÂ®, Crucell's management has decided to further postpone the registration submission of the Yellow Fever vaccine in Switzerland. MoRuViratenÂ® was successfully licensed in the first half of 2007 and its registration was renewed.
- AdVacÂ®/PER.C6Â® Technology-Based Ebola Vaccine : For the Phase I study for the Ebola vaccine, which Crucell is currently developing in partnership with the Vaccine Research Center (VRC) of the National Institute of Allergy and Infectious Diseases (NIAID), two groups of 16 volunteers have been enrolled and vaccinated. The clinical data is still blinded, however initial indications suggest that the vaccine is safe at the tested doses and appears to be immunogenic in a subset of subjects.
- AdVacÂ®/PER.C6Â® Technology-Based Tuberculosis Vaccine: Â The development of this vaccine is being carried out in collaboration with the Aeras Global TB Vaccine Foundation. A US Phase I trial (in BCG naÃ¯ve individuals) has been completed. The results of the trial, which will be presented by Aeras in April 2008 at a TB vaccines conference in Atlanta, indicate that the vaccine is well tolerated and capable of stimulating cell mediated response to tuberculosis antigens.Â In Q2 2007 a second clinical trial was initiated in South Africa. This Phase I trial is a placebo controlled study in adults who were vaccinated at birth with the BCG vaccine. Enrolment has been completed and follow up is ongoing. The study shows the vaccine to be well tolerated. A new Phase I BCG-Ad35 prime boost clinical trial of the unique AdVacÂ®-based tuberculosis vaccine was initiated in December 2007.
- AdVacÂ®/PER.C6Â® Technology-Based Malaria Vaccine: Crucell and its partner, the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), are conducting a Phase I trial in the U.S. The study is being carried out on two sites, VanderBilt and Stanford University. The first and second cohorts, comprising 18 and 17 volunteers respectively, have been successfully enrolled. No serious adverse side-effects have been reported to date. Current plans call for subsequent enrollment of two additional cohorts at higher vaccine doses, provided the vaccine has an appropriate safety profile. Following review of the safety data by a Safety Monitoring Committee, a decision has been made to begin recruitment of the third cohort. Initial findings of this Phase I trial are expected to be available in 2008.
- Merck Ad5 HIV vaccine: Discontinued: Merck's HIV vaccine candidate was in phase I and II studies when discontinuation of the trials was announced on 21 September 2007. The discontinuation of the studies was not related to the use of Crucell's technology.
- AdVacÂ®/PER.C6Â® Technology-Based HIV Vaccine: The Investigational New Drug Application (IND) for Phase I of the trial with Harvard Medical School (supported by the NIH) has been approved by the FDA in January 2008. Phase I of the trial is expected to start before the end of the first quarter of 2008.