NEWS IN BRIEF

Ebola outbreak triggers new development programmes

MAPP Biopharmaceutical, Tekmira, GlaxoSmithKline (GSK) and a few others are ramping up very different Ebola drug- and vaccine-development programmes. The lowdown: With the Ebola outbreak spreading across West Africa, the World Health Organization (WHO) has declared a global emergency. The epidemic has kick-started the development of several experimental medicines, even as global health experts continue to debate the practicalities and ethics of rolling these out to afflicted patients.

The only company so far to be able to extend its experimental treatment to patients in need has been MAPP Biopharmaceutical. MAPP Biopharmaceutical, in combination with LeafBio, Defyrus, the US government and the Public Health Agency of Canada, has developed a cocktail of three humanized monoclonal antibodies, each of which binds a different Ebola virus glycoprotein. The antibody serum, which is called ZMapp and is made in transgenic nicotine plants, has never been tested in humans before. The WHO has said that only 12 doses of the drug were available, but that this supply has already been exhausted.

Tekmira, too, is working to advance a possible treatment. Tekmira’s TKM-Ebola consists of small interfering RNAs that block the expression of the L protein of Ebola’s RNA polymerase and it has already been tested in healthy volunteers. The US Food and Drug Administration placed the Phase I drug on clinical hold in March, however, owing to concerns of cytokine release. In August, the regulators revised the restriction to a “partial hold” so that the drug may be used in infected patients (but not in healthy volunteers).

BioCryst is developing a small-molecule broad-spectrum antiviral that is targeted at viral polymerase, which could have utility against Ebola. The preclinical-stage drug is set to enter Phase I trials next year. MediVector is reported to be in discussion with regulators about using its Phase III small-molecule inhibitor of influenza viral polymerase, favipiravir, against Ebola as well.

On the vaccine front, GSK says that it is working to advance an adenoviral vector

vaccine into Phase I trials. GSK acquired the candidate last year through its purchase of Okairos, a vaccine developer. The vaccine consists of a non-replicating chimpanzee-adenovirus vector that has had two Ebola genes inserted into it. A trial could start “as early as Fall 2014” says the US National Institute of Allergy and Infectious Diseases, which has supported the development of the vaccine. The Public Health Agency of Canada is also making as many as 1,000 doses of a preclinical- stage recombinant vesicular stomatitis virus-based Ebola vaccine available to the WHO. Crucell and Profectus BioSciences are also working on Ebola vaccines.

FDA approves first PI3K inhibitor

But better biomarkers and rational combinations are still needed for the class to achieve its full potential.The lowdown: After many fits and starts for phosphoinositide 3-kinase (PI3K) drugs, the US Food and Drug Administration (FDA) has approved Gilead’s first-in-class idelalisib in combination with rituximab for chronic lymphocytic leukaemia (CLL). The FDA also granted accelerated approval for indolent non-Hodgkin’s lymphomas. The approvals were driven by strong clinical data and, despite considerable competition in the field, analysts now expect the drug to achieve annual global worldwide sales of US$1.3 billion by 2019 (Nature Rev. Drug Discov. 13, 162–164; 2014).

Idelalisib, which inhibits the p110δ subunit of PI3K, is also in Phase II development for Hodgkin’s lymphoma. A recent study showed that PI3Kδ modulates the antitumour immune response, which suggests that agents like idelalisib could have a role in solid tumours as well (Nature 510, 407–411; 2014).

Over a dozen other PI3K inhibitors, with a range of sensitivities against the four different isoforms of class I PI3K, are in development. Among the pan class-I-PI3K inhibitors, Novartis’s buparlisib is the most advanced: it is in Phase III trials for breast cancer and in Phase II trials for a range of solid tumours. Infinity’s IPI-145, which inhibits both PI3Kδ and PI3Kγ, is in Phase III trials for CLL and in Phase II trials for other blood cancers and inflammatory diseases.

N E W S & A N A LY S I S

644 | SEPTEMBER 2014 | VOLUME 13 www.nature.com/reviews/drugdisc

© 2014 Macmillan Publishers Limited. All rights reserved