AstraZeneca has entered into an agreement to acquire Novexel, a private infection research company in France, and will collaborate with Forest Laboratories on the future co-development and commercialization of two late-stage antibiotic development programmes; ceftazidime/NXL-104 (CAZ104) and ceftaroline/NXL-104 (CEF104). These antibiotic combinations utilise Novexel’s novel investigational beta-lactamase inhibitor NXL-104 to overcome antibiotic-resistance and treat the increasing number of infections resistant to existing therapies.
AstraZeneca has agreed to acquire 100 per cent of Novexel’s shares for US$ 350 million in cash payable at completion and will pay up to an additional US$ 75 million to Novexel shareholders if specified development milestones are reached. AstraZeneca will also transfer to Novexel shareholders an amount equivalent to the cash balance of Novexel at closing, approximately US$ 80 million. Under a separate agreement, AstraZeneca and Forest have agreed that following completion of the acquisition, Forest will pay Novexel, then an AstraZeneca group company, a sum equal to half of the acquisition costs of Novexel and half of any such specified development milestone payments in return for rights to CAZ104 in North America and the buy down of payment obligations in relation to CEF104 to Novexel from previous existing license arrangements. Effectiveness of the agreement is contingent on expiration or termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act.
CAZ104 is a combination of NXL-104 and ceftazidime, a third generation cephalosporin to which resistance has emerged. The addition of NXL-104 to ceftazidime extends its coverage of resistant Gram-negative pathogens including bacteria producing extended spectrum beta-lactamases. CAZ104 will be developed in serious infections requiring intensive care unit stays such as intra-abdominal, urinary tract and hospital acquired pneumonia. It is expected to move into phase-III development in late 2010 and to be filed with regulators in the US and EU in 2012.
CEF104 is a combination of NXL-104 and ceftaroline, Forest’s broad spectrum anti-MRSA cephalosporin which is currently in late stage development. The addition of NXL-104 is designed to enhance the Gram-negative activity of ceftaroline to include resistant Gram-negative pathogens. The combination will be developed in indications where a mixed Gram-negative and Gram-positive profile can be of use, such as skin and diabetic foot infections. It is expected to move into phase-II development in late 2010.
Development costs of the two combination treatments will be shared between AstraZeneca and Forest. Forest will have rights to commercialize the antibiotic combinations in North America while AstraZeneca will have rights to commercialize these products in the rest of the world with the exception of CEF104 in Japan, where Takeda retains the rights for ceftaroline. AstraZeneca also will pay undisclosed royalties to Forest on AstraZeneca’s international sales of the NXL-104 and ceftaroline combination. In addition to NXL-104 and its combinations, the Novexel pipeline includes a phase-II oral anti-MRSA compound and several early stage and preclinical compounds.
Forest signed an agreement with Novexel in January 2008 granting Forest rights to develop CEF104 in North America. AstraZeneca entered into an agreement with Forest in August 2009 to secure the rights to commercialize ceftaroline outside North America and Japan.
“Building AstraZeneca’s anti-infective portfolio has become a strategic priority as antibiotic-resistant bacteria poses a growing threat to human health,” said Anders Ekblom, AstraZeneca executive vice-president of Development. “The innovative structure of this agreement allows us to build on our existing collaboration with Forest to create value, share costs, and reduce exposure to risk while developing two novel antibiotic combinations that address a growing problem for clinicians and patients. Utilising Novexel’s NXL-104, these combinations have the potential to outwit bacteria that would otherwise be resistant to antibiotics.”
As a class, beta-lactam antibiotics such as cephalosporins, penicillins and carbapenems have been very successful in treating bacterial infections.
Gram-positive bacteria, of which MRSA is just one example, are often the primary pathogens in skin, sinus, ear, and outpatient lung infections.