Virus World

Takeda has scored the first-ever FDA approval of a treatment for refractory cytomegalovirus (CMV) infections in organ transplant patients, which can lead to an increased risk of complications and even death. Livtencity (maribavir) has been cleared for use in transplant patients aged 12 or over with CMV infections that do not respond to first-line treatment with current antiviral drugs for CMV, such as ganciclovir, valganciclovir, foscarnet and cidofovir. The FDA followed its advisory committee’s advice and backed Livtencity for use regardless of whether patients are infected with CMV strains that have resistance mutations, as checking for these could delay treatment. Maribavir works by blocking the activity of a CMV enzyme called pUL97 that is essential for replication of the virus, and also avoids some of the serious haematological side effects that are associated with the older antivirals. It was one of the drugs acquired by Takeda when it merged with Shire in 2019. The approval marks the culmination of a lengthy development for a drug that failed a phase 3 trial more than a decade ago for CMV prevention in hematopoietic stem cell transplant (HSCT) recipients.

Originally developed by GlaxoSmithKline, it was licensed to ViroPharma, which was subsequently bought put by Shire. The approval is based on the phase 3 SOLSTICE trial. which showed Livtencity was superior to conventional antiviral therapies in refractory CMV. More than 55% of transplant recipients with refractory infections achieved confirmed viral clearance with Takeda’s drug, compared to around 24% of those on the older drugs. CMV is one of the most common and serious post-transplant infections with an estimated incidence rate of between 16% and 56% in solid organ transplants, and 30% to 70% in HSCT procedures. Livtencity is one of Takeda’s ‘Wave1’ of new therapies that the company said a couple of years ago could collectively add more than $10 billion in aggregate peak sales, and the drugmaker has previously predicted sales revenues from the drug could top $700 million a year at peak. There’s no word yet on pricing, but Takeda said it would launch the drug “in the coming days.”

Although none of the coronavirus vaccines under development has proved its efficacy yet in clinical trials, at least 5.7 billion doses have been pre-ordered  around the world. First shipments of a COVID-19 vaccine created by Western laboratories have often been snapped up by the United States. Five vaccines — three Western and two Chinese — are in Phase 3 efficacy trials involving thousands of people. In a surprise announcement, Russian President Vladimir Putin claimed Tuesday that a vaccine dubbed Sputnik V — after the Soviet satellite — conferred “sustainable immunity” against the novel coronavirus. As research laboratories around the world race to develop a vaccine, manufacturers have received financing to help them prepare to have millions of doses ready to administer in 2021 or even before the end of the year.

Oxford University, working with the Swedish-British pharmaceutical group AstraZeneca, hopes to have results by September, while the US biotech company Moderna, partnering with the U.S. National Institutes of Health (NIH), is aiming for the end of the year, possibly November. U.S. President Donald Trump has launched “Operation Warp Speed” in a bid to develop, manufacture and distribute a COVID-19 vaccine to all Americans by January 2021. Hundreds of millions of dollars have been directed to vaccine developers, including nearly $500 million to Johnson & Johnson at the end of March. The United States has allocated funding to more companies than any other nation in the hope that one of them will come up with the vaccine to counter the highly contagious virus. So far, Washington has handed out at a total of at least $9.4 billion to seven vaccine developers and signed manufacturing contracts with five of them to provide 700 million doses. The companies involved are: Johnson & Johnson, Moderna, Oxford/AztraZeneca, Novavax, Pfizer/BioNTech, Sanofi/GSK, Merck Sharp and Dohme.  Two vaccine developers — Oxford/AztraZeneca and Sanofi/GSK — have signed or are in advanced negotiations with the European Commission to provide a combined 700 million vaccine doses. Britain, because of Brexit, is negotiating a separate pre-order of 250 million doses from four developers.  Japan is counting on 490 million doses from three suppliers, including 250 million from Novavax of the United States. Pharmaceutical giant Takeda bought the rights to a Novavax vaccine for Japan, which has funded the research. It would be produced locally.

Brazil chose a similar model, ordering 100 million doses from AstraZeneca and partnering with China’s Sinovac to produce 120 millions of CoronaVac, which is already undergoing testing with Brazilians. Clinical tests of two Chinese vaccine candidates — Sinovac and Sinopharm — are well underway but only a few international partnerships have been announced, the one with Brazil and a possible one with Indonesia. Russia said 20 nations have pre-ordered 1 billion doses of Sputnik V and that with foreign partners it would be able to produce 500 million doses a year in five countries. The Coalition for Epidemic Preparedness Innovations, launched in 2017 by Norway, India, the Bill and Melinda Gates Foundation and the Wellcome Trust, seeks to ensure that there is “equitable access” to future vaccines. It has pre-ordered 300 million doses from AstraZeneca for dozens of developing countries in a partnership with The Vaccine Alliance. Billions of doses would be produced for Asia and elsewhere by the giant Serum Institute of India (SII), the largest vaccine producer in the world. Novavax and AstraZeneca have separately signed agreements with SII to produce a billion doses each for India and low- and middle-income countries on the condition that they prove their efficacy in clinical trials.