Noemie Bisserbe and Betsy McKay
February 2, 2016
Drug companies are beginning early-stage research to develop a new vaccine against the rapidly spreading Zika virus, joining the race to control an outbreak that the World Health Organization said constitutes a global public-health emergency. Research is only at the preliminary stage at this moment in time, which suggests we are a long way from having inter partes reviews conducted on any important patent applications.
It might be years, however, before any vaccine reaches the market, meaning the new wave of research is unlikely to help curb the current outbreak. Though Zika generally makes people only mildly ill for a few days, it has been linked to a serious birth defect in which babies are born with undersized skulls and brains.
Zika’s explosive spread could give pharmaceutical companies a new opportunity in an increasingly important category of drugs, but the impact of a vaccine would depend on the prevalence of the virus when it hit the market, and the ability and willingness of governments to launch massive vaccination campaigns.
To attack Zika, French drugmaker Sanofi SA said Tuesday it would take advantage of the research it did for its newly approved vaccine for dengue fever—the world’s first against the mosquito-borne illness. The Zika and dengue viruses are in the same family.
“Theoretically, there could be some cross immunity,” said Nicholas Jackson,global head of research at the company’s Sanofi Pasteur vaccines unit, who will be running the new project. “We will need to investigate this clinically.”
Michael Diamond, an infectious-disease specialist at Washington University in St. Louis, said Sanofi’s expertise on the dengue virus would likely give it a head start in developing a Zika vaccine. But he also cautioned that Zika’s similarity to dengue would add complexity to vaccine development. The two viruses’ close resemblance means researchers would need to establish whether a Zika vaccine would be as effective in people with existing dengue immunity, and also whether immunity to Zika could affect how people respond to the dengue virus. “That’s going to have to be studied,” he said.
U.S. biotech company NewLink Genetics Corp. said it too was working on developing treatment options for the disease.
NewLink’s infectious-disease team felt that searching for a Zika vaccine “was a project they could really sink their teeth into,” said Charles Link, the company’s chief executive.
NewLink hasn’t begun human testing of any potential Zika vaccine candidates. “This is going to take some time and effort,” said Dr. Link. “This is not going to be an overnight deal.”
Epidemic diseases generally draw little investment from pharmaceutical companies because demand for those products is sporadic and unpredictable.
The WHO, the U.S. government, the pharmaceutical industry and others are working on ways to improve research and development for epidemic diseases, in the wake of the Ebola crisis in West Africa and as new epidemics such as Zika emerge.
At least a dozen Ebola vaccine and drug candidates were under development when the virus began to spread in West Africa.
Even so, there is still no licensed treatment or vaccine. One vaccine candidate, developed by NewLink and licensed out to Merck & Co. proved effective in a clinical trial, and the company is gathering data to apply for licensure.
The WHO, the United Nations public-health agency, acting on the recommendations of an emergency committee, on Monday called for more surveillance, research and efforts to control the virus’s spread. Currently, there are no rapid and reliable diagnostic tests, drugs or vaccines for Zika.
Last month, GeneOne Life Science Inc., a South Korean biopharmaceutical company, said it had launched a joint research program with U.S. biotech firmInovio Pharmaceuticals to develop a DNA-based vaccine to prevent and treat the Zika virus infection. U.K. drugmaker GlaxoSmithKline also said last week that it was assessing its research platform for the potential to develop a Zika vaccine.
The U.S. National Institutes of Health also is accelerating research into rapid diagnostic tests, vaccines, and therapeutic drugs for Zika, said Anthony Fauci,director of the National Institute of Allergy and Infectious Diseases, an arm of the NIH.
The NIH has long conducted research into flaviviruses, the class of viruses to which Zika belongs, with about $97 million in funding in fiscal 2015. But none was going into Zika, Dr. Fauci said.
The institute is pursuing two different pathways to a Zika vaccine, and may get one into an early Phase I clinical trial this year, he said. But, he cautioned: “We will not have a widely available safe and effective Zika vaccine this year and probably not even in the next few years.”
The once-obscure virus has become a major global health concern over the past few months, mainly because of its possible links to microcephaly in babies and Guillain-Barré, a rare disorder in which the body’s immune system attacks nerve cells.
Health authorities in Brazil, where as many as 1.5 million people may be infected with the Zika virus, have confirmed 404 cases of microcephaly since October.
Brazil isn’t alone. Authorities now say they believe that some cases of microcephaly in babies in French Polynesia may be linked to an outbreak of Zika that occurred there in 2013 and 2014. Brazilian and international health authorities also say Zika may be linked to a rise in the number of cases of Guillain-Barré syndrome.
Dr. Fauci said Zika is “the latest of a series of mosquito-borne diseases that have expanded their reach in the past 20 years or so.” It follows dengue and chikungunya, he said.
“There will almost certainly be others,” he said. “We need vaccine platforms that can be quickly modified for protection against emerging new threats and we need broad spectrum antiviral drugs effective against whole classes of viruses.”
—Peter Loftus and Denise Roland contributed to this article.
February 3, 2016
NewLink Genetics Corp. is not just another company jumping on the bandwagon of the latest global health crisis – in this case, the Zika virus, a mosquito-borne illness rapidly spreading throughout Central and South America and certain US territories, with the first continental US transmission of the disease reported on Feb. 2, which apparently involved sexual contact.
Indeed, the Ames, Iowa-based biotech, which recently gained worldwide recognition for its experimental Ebola vaccine – which so far has shown to be the most effective among those that have been tested in the past year – comes to Zika with one of the most experienced and knowledgeable vaccine development teams working in flaviviruses.
“I’ve got what I call a flavivirus dream team,” declared Thomas Monath, chief scientific officer and chief operating officer at NewLink’s infectious disease division.
In Monath’s past life, he was the chief science officer at Acambis Inc., a publicly traded company that was acquired in 2006 by Sanofi-Pasteur, the vaccines division of Paris-based Sanofi SA.
While at Acambis, Monath led the development of the ChimeriVax flavivirus platform on which Sanofi’s now-successful dengue vaccine, Dengvaxia, was based.
Dengvaxia is the only approved dengue vaccine in the world – winning regulatory nods this past December in Mexico, The Philippines and Brazil.
Monath said the ChimeriVax flavivirus platform – which he called “my baby” – also was used to make vaccines against Japanese encephalitis and West Nile, although the latter is only used in animals, with the world still waiting for a product for humans.
Sanofi itself on Feb. 2 announced it, too, was launching a Zika vaccine project based on its dengue platform – declaring that its “expertise and established R&D and industrial infrastructure” for Dengvaxia could be “rapidly leveraged to help understand the spread” of the Zika virus “and potentially speed identification of a vaccine candidate for further clinical development.”
Monath said he brought along a “number” of his Acambis/Sanofi teammates to work with him at NewLink. And he convinced other colleagues to join him from another of his former companies, Xcellerex Inc., where he led the development of a yellow fever vaccine.
“So we’ve got a lot of expertise and experience in making vaccines against viruses like Zika,” declared Monath, a world-renowned virologist and vaccinologist, who before joining industry spent 20 years with the US federal government at the Centers for Disease Control and Prevention and the US Army Medical Research Institute of Infectious Diseases.
Investors apparently have faith the company can do the job – driving shares of NewLink up 7.3% on Feb. 2, before closing at $25.70, a gain of $1.28, or 5.2%.
A Different Approach
Instead of pursuing a live-attenuated vaccine – the approach used for Dengvaxia and for one of the two Zika vaccine candidates the National Institute of Allergy and Infectious Diseases (NIAID) currently is working on – NewLink plans to develop a non-replicating whole virus particle product, Monath explained.
“At the end of the day, we want a vaccine that can be given to pregnant women,” he said, noting what the World Health Organization (WHO) has called a “strongly suspected” link between Zika in pregnant women in Latin America and microcephaly, a congenital condition in which babies are born with abnormally small head, which often is associated with incomplete brain development.
Because of the more than 4,000 cases of microcephaly and neurological complications in infants in Brazil and the “strong association” with Zika, the WHO on Feb. 1 declared a “public health emergency of international concern” – hoping that by doing so, governments, researchers and industry would make a coordinated global effort to quickly develop diagnostics, therapeutics and vaccines.
With no clear understanding of how the virus may be causing the microcephaly, Monath said it may be “very, very difficult” to ensure a live-attenuated Zika vaccine is safe for pregnant women and won’t cause damage to the fetus.
“Therefore, I would prefer to start from the technology that was not complicated by those safety questions,” he said. “I think that’s the surest way to get a vaccine out there that will work.”
Monath emphasized that he wasn’t saying a live-attenuated Zika vaccine couldn’t be developed.
“I think they can,” he said. But, Monath added, “it’s going to take a longer haul.”
A non-replicating Zika vaccine, he said, also may have a somewhat better storage and management advantage over a live-attenuated vaccine, which must be freeze-dried or frozen at a low temperature.
And, Monath said, a non-replicating Zika vaccine also may “get to the finish line the quickest.”
Partners And Incentives
Like NewLink did with its Ebola vaccine – a product it licensed from the Canadian government and later partnered with Merck & Co. in developing, with financial support from the US federal government – the biotech likely will seek collaborators for its Zika vaccine, Monath said.
NIAID chief Anthony Fauci last week told Scrip there’s been a ” considerable amount of interest” from industry in taking Zika vaccine candidates through advanced development.
GlaxoSmithKline PLC is one firm that’s expressed interest in possibly taking on the challenge of developing a Zika vaccine, although it’s unclear currently whether it would produce its own product or partner with the NIAID, like it did with Ebola.
NIAID, which last month issued a call for researchers and industry to pursue “vital areas” of Zika R&D, declaring it would provide grants for the work, currently is staying mum about what companies it’s been in discussions with over the past few weeks.
It’s unclear whether President Barack Obama will call for other Zika funding in his fiscal year 2017 budget proposal, due out next week.
But some lawmakers have proposed providing incentives to companies to entice them to develop a Zika vaccine, like an FDA priority review voucher (PRV).
Reps. GK Butterfield and Susan Brooks (R-IN) introduced a bill on Feb. 2 to add Zika to the list of diseases eligible for the tropical disease PRVs, the holders of which can use them on a subsequent application that otherwise would not have qualified for a priority review – shaving off as much as four months from the FDA’s examination process – or sell them to the highest bidder.
While NewLink is in the early R&D stages of its Zika vaccine, Monath insisted “We have the right people on board who have done this before, we’ve got the expertise and we’ve got the roadmap in place.”
So, he said, “that’s really going to facilitate the development program.”
February 3, 2016
Rising concern over the spread of the Zika virus, crystallized by Monday’s World Health Organization (WHO) labeling of it as a public health emergency, has jumpstarted efforts at Sanofi SA, Glaxosmithklineplc, Newlink Genetics Corp., Mymetics Corp. and Valneva SE to develop new vaccines against the dengue-related virus as interest from multiple quarters, including Congress, grows.
The WHO had estimated that as many as 4 million people could be affected by the virus as it spreads in Latin America and the Caribbean to North America in the coming months. So far, there is no vaccine or specific treatment for Zika nor an approved test for detecting infections before they become acute, for now leaving vector control as one of the most important means of potentially controlling its spread.
Sanofi said its Lyon, France-based Sanofi Pasteur division, a top supplier of vaccines for viruses in the same family as Zika virus, would work on the project. The company plans to leverage established R&D and industrial infrastructure put into place for its newly licensed vaccine for dengue, Dengvaxia, to potentially speed identification of a vaccine candidate for further development against Zika. (See BioWorld Today, Dec. 11, 2015.)
Sanofi spokeswoman Marisol Peron told BioWorld Today the company’s preventive vaccine in research and development for Zika is just at the starting line. “Although the scientific and public health communities agree that there are too many unknowns about Zika right now to reliably judge the ability to research and develop an effective vaccine,” she said that Sanofi Pasteur’s extensive experience in developing vaccines for flaviviruses, such as dengue, could potentially accelerate vaccine development for Zika.
GSK, another of the world’s largest developers of vaccines, is also said to be evaluating whether its vaccine technology is suited to the Zika virus.
Newlink’s infectious disease division, based in Devens, Mass., is evaluating various approaches for preventing Zika infection, too. Newlink’s chief scientific officer and chief operating officer, Tom Monath, told BioWorld Today the company has “a flavivirus dream team,” assembled from scientists, including Monath, who developed vaccines for three different flaviviruses during their employ at Acambis Inc., which was later acquired by Sanofi.
Monath said his team believes a nonlive, nonreplicating vaccine will be the best approach, given that it could be used safely during pregnancy and that probably it will take a couple years before the first clinical trial. “Until such time as we in the scientific community understand why microcephaly results from Zika virus infection, it poses a number of safety questions for any new vaccine, especially live viral vaccines with Zika proteins in them,” he said.
The company, which in 2014 joined forces with Merck & Co. Inc. to develop VSV-EBOV for Ebola, gained what Newlink CEO Charles Link said was “considerable experience during the Ebola crisis collaborating with national and international partners in a rapidly evolving public health environment.” Whether or not Newlink would leverage its internal resources or seek to move a potential Zika vaccine ahead with a partner is unknown at this point. (See BioWorld Today, Nov. 25, 2014, and Aug. 3, 2015.)
Though not committing quite yet, Lyon, France-based Valneva SE also suggested it might join the search for a Zika vaccine on Tuesday, noting that Zika is related to the Japanese encephalitis virus, another arthropod-borne flavivirus transmitted through mosquito bites, against which it has already developed a vaccine marketed as Ixiaro and Jespect. Considering what it called “the alarming spread of the Zika virus and the immediate medical needs,” Valneva said it would evaluate the technical feasibility of developing a vaccine and delivering a lead candidate within two years.
Other companies announcing plans to either join the project or explore it on Tuesday included Mymetics Corp., which, following notice of a terminated respiratory syncytial virus vaccine program on Jan. 28, said it has started to investigate Zika, too.
The companies join ongoing work at Replikins Ltd. and a partnership between Inovio Pharmaceuticals Inc. and Geneone Life Science Inc., which a representative of Inovio told BioWorld Today is evaluating a vaccine candidate in animal testing with hopes of beginning a trial before the end of 2016. (See chart, below.)
Alongside work to develop vaccines, diagnostics makers have also been busy. The first in vitro diagnostic tests began shipping last week to labs in Brazil and other regions where the mosquito-borne infection has become epidemic, while Genekam Biotechnology AG, Altona Diagnostics GmbH and Vela Diagnostics Pte. Ltd. all have PCR-based diagnostics in varying stages of development. Though good for detecting acute viral infections, such tests may face challenges in making a big impact because it is difficult to detect asymptomatic infections, something which could be common if a well-studied past outbreak is a guide. (See BioWorld Today, Feb. 2, 2016.)
Behind the scenes, public health experts such as Bruce Aylward, executive director ad interim of WHO’s Outbreaks and Health Emergencies Cluster, are working to coordinate the global research community, industry, public sector and others in much the same way as was done during the Ebola crisis to “really look at [whether there] is merit for an accelerated product development agenda around this,” he told reporters during a Feb. 1 press briefing.
Aylward said that vaccine development is known to be “a 12-month-plus” project. “The time frame for developing a new diagnostic, if it’s technically feasible to have a better antibody detection: Well,” he said, “that should be shorter than that but we really need right now to be working with the tools that we have and we certainly have the tools to understand and diagnose infection.”