Approvals are also in the offing for Abbvie Inc., for Rinvoq (upadacitinib, ABT-494), its selective JAK1 inhibitor, in rheumatoid arthritis; for Eli Lilly and Co., for Baqsimi (glucagon), its nasally administered rescue therapy for severe hypoglycemia; for Johnson & Johnson's Spravato (esketamine), its depression drug, which is also nasally administered; and for A. Menarini Industrie Farmaceutiche Riunite Srl's antibiotic, Quofenix (delafloxacin), for treating bacterial skin and skin structure infections. Amgen Inc. and UCB SA have prevailed in their re-examination request, getting a positive vote at the second time of asking for Evenity (romosozumab) for treating osteoporosis.
The Merck vaccine, which comprises a replication-competent recombinant vesicular stomatitis (VSV) vector expressing Zaire Ebola virus glycoprotein, was originally developed at Canada's National Microbiology Laboratory, in Winnipeg, Manitoba, and licensed first to Ames, Iowa-based Newlink Genetics Inc. The latter subsequently entered a deal with Merck in late 2014, at the peak of the 2013-2016 epidemic in West Africa. A phase III field trial conducted during the epidemic, involving 5,837 individuals, appeared to provide 100% protection after a single shot. None of those who received the vaccine became infected, whereas 23 cases occurred in a control group who received the vaccine 21 days after randomization. In all, about 16,000 individuals in Africa, Europe and the U.S. have received the vaccine in clinical studies.
An FDA review of Ervebo is ongoing, with a PDUFA date of March 14, 2020. Merck is working with the World Health Organization (WHO) to achieve prequalification status and is also working with the African Vaccine Regulatory Forum, a capacity-building organization founded by the WHO in 2006 to improve regulatory oversight of trials being conducted in African countries.
Innovation alone is, of course, no match for a public health crisis when other countervailing factors are also in play. Although the WHO and its local partners were much better prepared to deal with the current, ongoing outbreak in the Democratic Republic of the Congo (DRC) than it was with the West African outbreak, their efforts to contain the epidemic have been undermined by military conflict and cultural and communications difficulties in North Kivu, South Kivu and Ituri provinces. Merck has already shipped more than 236,000 doses to the DRC and bordering countries Uganda, Burundi and Rwanda.
As of last Wednesday, the total number of cases had reached 3,227, according to WHO figures, including 3,113 confirmed and 114 probable cases, while the total number of deaths had reached 2,154, implying a case fatality rate of 67%. It is, by some ways, the second largest Ebola outbreak ever and the largest ever in the DRC, from where the virus is thought to have originated.
The true picture could even be worse, however, as reliability of those numbers is in doubt. A recent field survey in some of the areas affected by the outbreak revealed a widespread lack of understanding among the local community and health care workers about Ebola's transmission mechanism and about the symptoms of Ebola infection. The WHO has also detected mistrust about the origins of the disease and the need for vaccination. It is therefore difficult to judge whether a decline in reported new cases in recent weeks indicates that the outbreak has already passed its peak or whether the real picture is still hidden.
Mostly predictable nods
Several of this month's positive votes are predictable, trailing FDA approvals by a matter of months. Abbvie, of North Chicago, previously gained FDA approval for Rinvoq in August. J&J, of New Brunswick, N.J., gained FDA approval for Spravato in March. And Lilly, of Indianapolis, gained FDA approval for Baqsimi in July. The latter serves as a rescue therapy for treating patients with type 1 or type 2 diabetes who experience severe hypoglycemia. The drug, the first non-injectable treatment for severely low blood sugar levels, can be administered by caregivers to patients who have lost consciousness. Lilly acquired global rights to the product in 2015 from Montreal-based specialty pharma firm Locemia Solutions ULC.
Quofenix has taken a far more circuitous route toward a European approval, having passed through the hands of several drug developers. Morristown, N.J.-based Melinta Therapeutics Inc. gained an FDA approval for the product 2017. It is marketed in the U.S. as Baxdela.
Brussels-based UCB and Amgen, of Thousand Oaks, Calif., have a route to market in Europe for Evenity. Approval of the sclerostin inhibitor was delayed by unexpected cardiovascular problems identified in a phase III trial in 2017, which prompted an FDA complete response letter. The drug eventually got over the line in the U.S. in April, although its label carries a black box warning that it may increase the risk of heart attack, stroke and cardiovascular death. It was initially rebuffed by the CHMP in June. Its safety issues will probably confine its use to high-risk patients with no history of cardiovascular disease.
The CHMP was less generous with PTC Therapeutics Inc., of South Plainfield, N.J., which had requested a re-examination of an application to extend the label for Translarna (ataluren) to patients with Duchenne muscular dystrophy who were no longer able to walk. The initial application was rebuffed in June.