Aeras and Crucell Announce Start of Phase II TB study in South Africa

Aeras and Crucell Announce Start of Phase II TB study in South Africa
Leiden, the Netherlands (April 14, 2010) - Dutch biopharmaceuticalcompany Crucell N.V. (NYSE Euronext, NASDAQ: CRXL; Swiss Exchange: CRX)and the Aeras Global TB Vaccine Foundation today announced the start of aPhase II clinical trial of the jointly developed tuberculosis (TB) vaccine candidateAERAS-402/Crucell Ad35 in HIV infected adults.


The Phase II study is designed to test the safety and efficacy of AERAS-402/Crucell Ad35 in adults infected with HIV and will be conducted by the AurumInstitute in Klerksdorp, South Africa. All Aeras-sponsored TB vaccine candidateshave been or will be tested for safety in people living with HIV. Among peopleliving with HIV in Africa and Asia, TB is a leading cause of death. People with HIVliving in countries with high TB prevalence are 20 times more likely to develop TBthan those who are HIV-negative. According to the World Health Organization's(WHO) 2009 TB surveillance report, one in four TB deaths globally is HIV-related,twice as many as previously recognized. In 2007, there were an estimated 1.4million new cases of TB among people living with HIV and 456 000 deaths.Seventy-one percent of people with TB in South Africa are co-infected with HIV.


"With the support of Crucell's innovative technologies, we are on a joint missionwith Aeras to develop a next generation vaccine against TB," said Dr. JaapGoudsmit, Crucell's Chief Scientific Officer. "As there are many potential uses ofthe new TB vaccine, it is crucial to test the safety and immune responses in thosewho have been infected with HIV. That is why we are extremely pleased with theinitiation of this Phase II study, an important next step towards our ambition ofreducing the global burden of this fatal disease."


Enrollment of study volunteers for the first stage of the Phase II trial has started.This is the first study testing the AERAS-402/Crucell Ad35 TB vaccine candidateamong this study population.


In 2004, Aeras and Crucell began jointly developing this vaccine candidate usingCrucell's AdVac® vaccine technology and PER.C6® manufacturing technology. Datafrom all AERAS-402/Crucell Ad35 trials support the immunogenicity and acceptable safety profile of the TB vaccine candidate at all dose levels evaluated.

 

AERAS-402/Crucell Ad35 trials.

In October 2008, the first Phase II study in adults who have had active TB startedin South Africa. In this ongoing study, AERAS-402 has demonstrated anacceptable safety profile. Preliminary data indicate that the candidate vaccineinduces CD8-cell immune responses in patients who have completed TBtreatment.
 
To date, seven Phase I studies have been conducted in populations including healthy adults and infants and adult tuberculosis patients:


• A trial in healthy adults not previously immunized with Bacille Calmette-Guérin (BCG), the traditional TB vaccine, demonstrated that the candidatevaccine had an acceptable safety profile in this population.


• A South African study showed CD8 T cell immune responses that are much higher than those seen in humans in any previous TB vaccine study.


• US studies in healthy adults, focusing on the immunogenicity and safety of two boost doses after BCG priming, showed that two injections of the candidate vaccine are immunogenic, with an acceptable safety profile, when used in combination with a BCG prime, regardless of the boosting interval. This immune response is greater than that detected in theabsence of BCG prime, supporting the possible utility of AERAS-402/Crucell Ad35 as a booster vaccine. BCG prime alone shows limited efficacy.


• Testing of the candidate vaccine's safety in BCG-vaccinated adults with or without latent TB has been completed in Kenya, with ongoing analysis. The vaccine had an acceptable safety profile in this study.


• A trial in South Africa is testing the safety of the candidate vaccine in infants previously vaccinated with BCG vaccine. The study is fully enrolled and dosing is ongoing. To date, the vaccine appears to have an acceptable safety profile in this study.


• Currently a US trial has started for more detailed analysis of the immune response to AERAS-402/Crucell Ad35, using a known immunogenic regimen of BCG and the candidate vaccine in healthy adults, followed by collection of large numbers of immune cells.

About Tuberculosis

 
Tuberculosis is the world's second deadliest infectious disease, with nearly 9.3 million new cases diagnosed in 2007. According to the WHO, an estimated 1.8 million people died from TB in 2007. One-third of the world's population has been infected with the TB bacillus and current treatment takes 6-9 months. The current TB vaccine, Bacille Calmette-Guérin (BCG), developed over 85 years ago,reduces the risk of severe forms of TB in early childhood but is not very effective in preventing pulmonary TB in adolescents and adults - the populations with the highest rates of TB disease. TB is changing and evolving, making new vaccines more crucial for controlling the pandemic. Tuberculosis is now the leading cause of death for people living with HIV/AIDS, particularly in Africa. Multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) are hampering treatment and control efforts.

 

About AdVac® technology and Ad35

AdVac® technology is a vaccine technology developed by Crucell and is considered to play an important role in the fight against emerging and reemerging infectious diseases, and in biodefense. The technology supports the practice of inserting genetic material from the disease-causing virus or parasite into a 'vehicle' called a vector, which then delivers the immunogenic material directly to the immune system. Most vectors are based on an adenovirus, such as the virus that causes the common cold. The AdVac® technology is specifically designed to manage the problem of preexisting immunity in humans against the most commonly used recombinant vaccine vector, adenovirus serotype 5 (Ad5), without compromisinglarge-scale production capabilities or the immunogenic properties of Ad5. AdVac®technology is based on adenoviruses that do not regularly occur in the humanpopulation, such as Ad35. In contrast to for instance Ad35 antibodies, antibodiesto Ad5 are widespread among people of all ages and are known to lower theimmune response to Ad5-based vaccines, thereby impairing the efficacy of thesevaccines. All vaccine candidates based on AdVac®are produced using Crucell'sPER.C6® production technology.

 

About PER.C6®technology

Crucell's PER.C6®technology is a cell line developed for the large-scalemanufacture of biopharmaceutical products including vaccines. The productionscale potential of the PER.C6®cell line has been demonstrated in anunprecedented successful bioreactor run of 20,000 liters. Compared toconventional production technologies, the strengths of the PER.C6®technology liein its excellent safety profile, scalability and productivity under serum-free cultureconditions. These characteristics, combined with its ability to support the growthof both human and animal viruses, make PER.C6®technology thebiopharmaceutical production technology of choice for Crucell's current andpotential pharmaceutical and biotechnology partners.


About Aeras

The Aeras Global TB Vaccine Foundation is a non-profit product developmentpartnership dedicated to the development of effective TB vaccine regimens thatwill prevent tuberculosis in all age groups and will be affordable, available andadopted worldwide. Aeras partners with academic, biotechnology, pharmaceuticalresearch institutes throughout the world to ensure rapid development and amplevaccine distribution to eliminate TB. Aeras receives funding from foundations andgovernment aid agencies and has six TB vaccine candidates in its product development pipeline. It operates from its headquarters in Rockville, Maryland, and an office in Cape Town, South Africa. For more information, please visitwww.aeras.org.

 

About Aurum Institute

Aurum is an internationally recognized, specialist research and health systemsmanagement organization. The focus is TB and HIV prevention, treatment andcare. The negative impact of the poor understanding and management of theseepidemics is vast, affecting individuals, communities and economies. Therecognition of the huge advantages of controlling these diseases is Aurum'smotivation. Aurum has an international reputation for its work in the fields oftuberculosis, HIV/AIDS and is the recipient of research and other grants fromSouth African and international agencies and institutions for this work. For moreinformation, please visit www.auruminstitute.org.

 

About Crucell

Crucell N.V. (NYSE Euronext, NASDAQ: CRXL; Swiss Exchange: CRX) is a globalbiopharmaceutical company focused on research development, production andmarketing of vaccines, proteins and antibodies that prevent and/or treatinfectious diseases. Its vaccines are sold in public and private markets worldwide. Crucell's core portfolio includes a vaccine against hepatitis B, a fully-liquid vaccineagainst five important childhood diseases and a virosome-adjuvanted vaccine against influenza. Crucell also markets travel vaccines, such as the only oralanti-typhoid vaccine, an oral cholera vaccine and the only aluminum-freehepatitis A vaccine on the market. The Company has a broad development pipeline, with several product candidates based on its unique PER.C6® productiontechnology. The Company licenses its PER.C6® technology and other technologiesto the biopharmaceutical industry. Important partners and licensees includeJohnson & Johnson, DSM Biologics, sanofi-aventis, Novartis, Wyeth, GSK, CSLand Merck & Co. Crucell is headquartered in Leiden, the Netherlands, withsubsidiaries in Argentina, China, Italy, Korea, Spain, Sweden, Switzerland, UKand the USA. The Company employs over 1200 people. For more information,please visit www.crucell.com.

 

Forward-looking statements

 

This press release contains forward-looking statements that involve inherent risks anduncertainties. We have identified certain important factors that may cause actual resultsto differ materially from those contained in such forward-looking statements. Forinformation relating to these factors please refer to our Form 20-F, as filed with the USSecurities and Exchange Commission on April 7, 2010, in the section entitled ‘RiskFactors'. The Company prepares its financial statements under International FinancialReporting Standards (IFRS).

company Crucell N.V. (NYSE Euronext, NASDAQ: CRXL; Swiss Exchange: CRX)and the Aeras Global TB Vaccine Foundation today announced the start of aPhase II clinical trial of the jointly developed tuberculosis (TB) vaccine candidateAERAS-402/Crucell Ad35 in HIV infected adults.The Phase II study is designed to test the safety and efficacy of AERAS-402/Crucell Ad35 in adults infected with HIV and will be conducted by the AurumInstitute in Klerksdorp, South Africa. All Aeras-sponsored TB vaccine candidateshave been or will be tested for safety in people living with HIV. Among peopleliving with HIV in Africa and Asia, TB is a leading cause of death. People with HIVliving in countries with high TB prevalence are 20 times more likely to develop TBthan those who are HIV-negative. According to the World Health Organization's(WHO) 2009 TB surveillance report, one in four TB deaths globally is HIV-related,twice as many as previously recognized. In 2007, there were an estimated 1.4million new cases of TB among people living with HIV and 456 000 deaths.Seventy-one percent of people with TB in South Africa are co-infected with HIV."With the support of Crucell's innovative technologies, we are on a joint missionwith Aeras to develop a next generation vaccine against TB," said Dr. JaapGoudsmit, Crucell's Chief Scientific Officer. "As there are many potential uses ofthe new TB vaccine, it is crucial to test the safety and immune responses in thosewho have been infected with HIV. That is why we are extremely pleased with theinitiation of this Phase II study, an important next step towards our ambition ofreducing the global burden of this fatal disease."Enrollment of study volunteers for the first stage of the Phase II trial has started.This is the first study testing the AERAS-402/Crucell Ad35 TB vaccine candidateamong this study population.In 2004, Aeras and Crucell began jointly developing this vaccine candidate usingCrucell's AdVac® vaccine technology and PER.C6® manufacturing technology. Datafrom all AERAS-402/Crucell Ad35 trials support the immunogenicity andacceptable safety profile of the TB vaccine candidate at all dose levels evaluated.AERAS-402/Crucell Ad35 trialsIn October 2008, the first Phase II study in adults who have had active TB startedin South Africa. In this ongoing study, AERAS-402 has demonstrated anacceptable safety profile. Preliminary data indicate that the candidate vaccineinduces CD8-cell immune responses in patients who have completed TBtreatment.


Related Stories
■Aeras Global TB Vaccine Foundation and The Aurum Institute Announce a New Collaboration to Conduct a Clinical Trial of TB Vaccine Candidate in People Living with HIV
■Crucell Program Leaves Positive "Footprint" in South Africa

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