Whatever Happened To Industry's Interest In Ebola?

The story of the year for the biopharmaceutical industry in 2015 was most certainly the rumpus over drug prices – whether it was the uproar over the jacked up costs of older products by Turing Pharmaceuticals AG and Valeant Pharmaceuticals International Inc. or the deals the new kids on the block, the proprotein convertase subtilisin/kexin 9 inhibitors, Sanofi SA's and Regeneron Pharmaceuticals Inc.'s Praluent (alirocumab) and Amgen Inc.'s Repatha (evolocumab), had to make with payers to get past the fray.

Indeed, the drug price debate in 2015 quickly muted the big biopharmaceutical industry conversation that dominated a year earlier – Ebola, which was driven mostly by public fear and the fact the World Health Organization (WHO) had almost nothing good to say about drug and vaccine makers, putting manufacturers under the microscope to prove their worth in a crisis.

The most recent Ebola outbreak is responsible for killing about 11,300 people, mostly in West Africa, and sickening nearly 29,000.

The WHO on Dec. 29 declared Guinea – the nation where the original chain of transmission started in late 2013 – free of Ebola.

Neighboring Sierra Leone was deemed free of the virus in November, while Liberia has twice been designated done with the disease, only to have it return – most recently the week of Nov. 22, when three new cases were reported. If there are no other cases confirmed, Liberia could again be declared Ebola-free on Jan. 14, 2016.

While WHO has admitted it made several mistakes in dealing with the crisis, one top official from the global agency in August 2014 declared Ebola a "market failure" – putting much of the blame for the out-of-control outbreak in West Africa at industry's feet.

But industry stepped up – with firms like Merck & Co., GlaxoSmithKline Plc , Johnson & Johnson Inc. and others jumping in to ensure drug and vaccine companies had a seat at the table, whether it was at the emergency WHO-convened meetings to figure out what to do to address the situation or working with the National Institutes of Health (NIH) and the Centers for Disease Control and Prevention (CDC) on accelerating the development and testing of investigational products that were, at the height of the Ebola panic in the fall of 2014, at the very early stages.

Suddenly, small companies like Tekmira Pharmaceuticals Corp. and Mapp Biopharmaceuticals Inc. were all the rage – with everyone wanting to get the funding attention those tiny firms were getting from investors and government agencies.

By the end of 2014, investigational drugs like Mapp's ZMapp, Fujifilm Holdings Corp.'s favipiravir and Chimerix Inc.'s brincidofovir and experimental vaccines from the NIH's National Institute of Allergy and Infectious Diseases (NIAID) and its collaborator GSK and NewLink Genetics Inc. and its partner Merck looked promising and offered new hope against the Ebola epidemic.

Is Industry Still Committed?

With a lot of quick work and collaboration, 2015 started off with much excitement that large-scale testing of the experimental medicines and vaccines would soon be underway.

But while the work moved forward on the vaccines throughout 2015, that wasn't the case for some of the investigational drugs – with Tekmira bowing out of Ebola R&D this past July and changing its name to Arbutus Biopharma Corp. and Chimerix halting its work on brincidofovir's use against the virus, returning to its key focuses for the drug, adenovirus and cytomegalovirus, although there's some question now about its future in the latter indication.

The US government has continued to pour money into ZMapp and similar antibodies from Regeneron. Fujifilm also recently reported more positive news about its antiviral in Ebola.

In July, researchers reported in the medical journal The Lancet that the Merck-NewLink Ebola vaccine, known as rVSV-ZEBOV, was 100% effective in protecting humans against the virus in the Phase III ring study.

The results of the study, supported and led by WHO, suggested the rVSV-ZEBOV vaccine protected adults potentially exposed to Ebola as early as 10 days after being vaccinated.

Another trial, known as PREVAIL – the Partnership for Research on Ebola Vaccines in Liberia – being run by the NIH and testing rVSV-ZEBOV and the NIAID-GSK vaccine cAd3-EBOZ, reported positive Phase II results in March and met its enrollment goal of 1,500 in May.

But because the virus had waned in West Africa, the trial has been unable to move into Phase III and determine efficacy of the products, said Cliff Lane, deputy director for clinical research at NIAID and the lead for the US-Liberian clinical research partnership overseeing the PREVAIL studies.

Nonetheless, the PREVAIL study has "continued to run quite well and follow-up has been quite good," Lane told Scrip. "We continue to generate data on the level of antibody responses and how long those antibody responses persist."

He noted that when the three new Ebola cases were reported in November in Liberia, the PREVAIL researchers amended the study's protocol to provide the Merck-NewLink vaccine to the contacts of those patients and the contacts of contacts.

"Public health experts thought that was a prudent thing to do," Lane said.

Where Do We Go From Here?

For now, the NIH and the PREVAIL team are in discussions about potentially conducting additional trials under a regional effort in West Africa, working in partnership with the three health ministries and other entities, like the London School of Hygiene and Tropical Medicine and the French Institute of Health and Medical Research, or INSERM, to see about doing some additional work, Lane explained.

"That's not really well-defined yet. It's just in the discussion stage," he emphasized, noting the path forward for further administering the experimental vaccines and getting them licensed or available under expanded access will depend on what the data currently being gathered show.

Lane also pointed out that it will be up to the vaccine sponsors to decide on whether they want to pursue licensure of the products in the US or elsewhere.

Meanwhile, another study testing the Merck-NewLink vaccine run by the CDC has completed its immunizations against Ebola of more than 8,000 study participants, with all vaccination sites now closed, spokesman Ian Branam told Scrip.

The study, known as STRIVE, which got underway in April, was being conducted at seven sites in five districts in Sierra Leone – all of which were opened by June 18, Branam said in an email response to questions.

In the study, participants were randomized to receive the vaccine immediately or in six months.

Enrollment in the STRIVE trial closed on Aug. 15, with 8,680 participants vaccinated. More than 4,150 of the participants were balloted to the immediate group, Branam said, although he noted those numbers could change with the final study reconciliation.

Vaccination of those balloted to the deferred group began on Sept. 19, followed by the reopenings of the six other sites. Vaccination of the deferred group ended on Dec. 12.

So far, STRIVE's safety profile is consistent with previous trials, Branam said.

Efficacy data from STRIVE are pending.

J&J in October also started a trial of its prime-boost vaccine regimen in Sierra Leone, which was initiated on parallel track with multiple ongoing Phase I and II studies across US, Europe and Africa as part of accelerated development plan for the product.

The study, dubbed EBOVAC-Salone, is testing the uses of a combination of two vaccine components based on AdVac technology from J&J subsidiary Crucell Holland BV and the MVA-BN technology from its partner Bavarian Nordic.

Volunteers in the study were first given the AdVac dose to prime their immune system and then the MVA-BN dose two months later to boost their immune response, with the goal of potentially strengthening and optimizing the duration of the immunity.

"Never again can Ebola be allowed to cause the human suffering that the world has witnessed in West Africa and we remain committed as ever to helping the international community combat this disease," said Paul Stoffels, chief scientific officer and worldwide chairman of pharmaceuticals at J&J. "One of the many lessons learned from the outbreak is we cannot let our guard down with Ebola, and we need to test every promising prevention tool."