Vaccines firm Intercell is ditching further development of its late-stage patch-based traveler’s diarrhea vaccine due to lack of efficacy in Phase III and Phase II studies evaluating its ability to protect against enterotoxigenic E. coli (ETEC). The firm will, as a result, lose out on the chance to earn any related milestone payments from GlaxoSmithKline (GSK), its development partner for the product since December 2009.
Intercell says failure of the traveler’s diarrhea vaccine at this late stage means it now plans to reduce its R&D spending in 2011 by about 40% compared with this year’s investment in research. However, it does aim to continue evaluating the patch technology for the delivery of other potential vaccine candidates, and for the development of an investigational Vaccine Enhancement Patch (VEP) system for vaccinating against avian H5N1 influenza. The firm will have to liaise with its partner GSK about the way forward.
Discontinuation of the diarrhea vaccine patch’s development comes on the release of data from the placebo-controlled Phase III ELT301 study involving 2,036 participants travelling from Europe to Mexico and Guatemala, and from a pilot Phase II study (ELT209) involving 723 individuals traveling from Europe to India. Neither trial met its primary endpoint of reducing the incidence of all types of ETEC infection, in which ETEC LT, LT/ST, or ST toxins were detected in diarrheal stool samples. The secondary endpoint of preventing all-cause diarrhea was also not met.
Intercell points out this data is in contrast to those from a previous Phase II study, ELT206, which evaluated the vaccine in participants travelling from the U.S. to Guatemala and Mexico. In this study the vaccine did appear to reduce the risk of clinically significant diarrheal episodes. Moreover, the firm stresses, the promising potential of patch-based immunization was evidenced by the fact that the trials confirmed that the patch technology consistently induced protective levels of antibodies against the LT-toxin following transcutaneous immunization.
“We are extremely disappointed with these unexpected Phase II and III outcomes for our traveler’s diarrhea vaccine patch,” admits Gerd Zettlmeissl, CEO. “We have taken all necessary managerial measures to fully realign the company’s operations.”
Intercell and GSK established a strategic alliance develop needle-free, patch-based vaccines in December 2009. In addition to the traveler’s diarrhea vaccine, the deal also covers investigational single-application pandemic influenza vaccine (currently in Phase II development), as well as the use of the patch technology for other vaccines in GSK's portfolio. Under the terms of the agreement, GSK paid Intercell $49.4 million up front, and was making a staged equity investment in its partner of about $123.5 million, for a 5% stake in Intercell.
Intercell’s product portfolio includes the marketed prophylactic Japanese encephalitis vaccine, trade named Ixiaro/Jespect. The firm reported product sales of €3.8 million in the three months ended September 30 2010, up from €2.7 million in the equivalent quarter in 2009. The firm is also progressing a clinical pipeline of in house and partnered vaccine candidates comprising prophylactic vaccines against S. aureus (Phase II/III), Pseudomonas (poised to start in Phase III development), tuberculosis (Phase II), and Pneumococcus (Phase I). A therapeutic vaccine targeting hepatitis C is currently in Phase II development. Additional vaccine and antibody candidates against a range of bacterial infections are in preclinical development, both through collaborative partnerships and in house.
The firm is separately carrying out pediatric Phase III clinical studies for Ixiaro/Jespect in children travelling to Japanese encephalitis endemic areas. Plans are also in place to start Phase III studies with a Japanese encephalitis vaccine candidate for people living in endemic areas. Intercell points out the World Health Organization has recommended that Japanese encephalitis vaccination is integrated into national immunization programs. To this end, the firm plans to start a pivotal Phase III trial in children by early 2011, which will be sponsored and managed by Intercell’s partner, Biological E., in India.