Wave of the future: The Ebola crisis as a tipping point for pharmaceutical R&D
The concept of Ebola-specific R&D aimed at developing vaccines and other preventive therapies, as well as treatments for Ebola, is barely a year old. But what a difference that year can make.
The 2014 Ebola outbreak, which peaked in intensity in fall 2014, is the worst in history. CDC experts estimate that since December 2013, approximately 10,000 people have died from Ebola and 25,000 people have been infected—with Guinea, Liberia and Sierra Leone, the hardest hit countries, facing staggering losses.
The response from the World Health Organization (WHO) was a little late, but intense and determined once it started. At the same time, the response from the pharmaceutical community was swift and largely collaborative. As the outbreak hit its apex, one company after another stepped forward with Ebola-related therapeutic interventions in various stages of development.
In fall 2014, there were three experimental drugs used to treat Ebola-infected patients, including TKM-Ebola from Tekmira, ZMapp from Mapp Biopharmaceutical and brincidofovir from Chimerix. The first patient to be diagnosed with Ebola in the U.S., Thomas Eric Duncan, was treated in October 2014 with brincidofovir, which was in phase III development for use against cytomegalovirus and adenovirus infections. (Note: Mr. Duncan died on October 8, 2014).
Progress in Ebola R&D continues
In February 2015, NewLink Genetics received a $20 million milestone payment from Merck—its Ebola vaccine (rVSV-EBOV) development partner—as it initiated clinical trials. This partnership, which dates back to November 2014, was also bolstered by NewLink’s other collaborative partners, including the National Institutes of Health (NIH), the WHO, and the Canadian government.
Although the crisis has begun to wane, and there are only a few cases of Ebola infection reported each week, the lesson has been learned: There is a need for antiviral R&D, because inevitably new epidemic and potentially pandemic infections will occur.
Fortunately, companies such as Seattle-based Kineta, a biotech company focused on the development of immune-modulating drugs, are focused on innovative anti-viral research. Kineta has a therapy in development, which may very well become the go-to treatment option when another Ebola outbreak occurs—or any other outbreak driven by filoviruses, flaviviruses or respiratory viruses. In fact, Kineta’s broad-spectrum antiviral program is being developed to inhibit not only Ebola, but also influenza A&B, dengue, West Nile, Lassa fever, respiratory syncytial virus (RSV) and various human coronaviruses.
Kineta’s broad-spectrum antiviral program
Dr. Shawn Iadonato, Chief Scientific Officer at Kineta, emphasizes that his company’s therapeutic platform is not a vaccine, nor is it a conventional direct-acting antiviral. He explains, “Our potent host-directed innate immune molecules offer broad-spectrum protection without development of drug resistance. Unlike currently available direct-acting antivirals, our approach is like a cocktail in a single therapy, which sets off a multifactorial response process.”
Focus on influenza
While Kineta is making headlines for its in vitro results demonstrating efficacy against the Ebola virus, in fact, this company, which was founded in 2008, did not start out focused on Ebola. According to Iodonato, most of Kineta’s early development work was in the area of influenza. However, Kineta eventually started working on antiviral programs as part of a larger biodefensive global health program, with a focus on West Nile Virus and dengue fever. As part of that program, Kineta received biodefense grants, some of which were used to fund Ebola-related research.
The challenge of many antiviral development programs is that they use direct activity and only inhibit a single step in a virus’s life cycle, with a well-characterized target and mode of action. However, this type of direct activity is only active against one or a few viruses. Even more serious, the threat of viral resistance is always lurking in the background.
In contrast, Kineta’s innate immune transcription factor (IRF-3)-mediated antivirals have dual activity focused on both inhibiting viral replication and activating immune cells for viral clearance. As a result, viral resistance is less likely.
In mouse models, the compounds were tested against influenza and dengue, and were both effective and well tolerated with a 100- to 1000-fold reduction in the amount of virus in the plasma and lungs. And when the compounds were tested again Ebola infection in tissue culture, there was a more than 100-fold reduction in viral load.
There’s another important difference. According to Iodonato, “During testing, we can clearly see that our program can be administered before or after infection and still have an antiviral effect.”
Looking beyond acute challenges
As a company that focuses on translational development, Kineta is looking towards a future based on partnership with a larger company. At this point, the plans are to transition from non-clinical to early clinical development in two years, with anticipated regulatory filings within seven years. On the upside, Kineta’s program will most likely qualify under various expedited review programs, as well as the Qualified Infectious Disease Program (QIDP).
The exciting thing about these compounds is that they represent an opportunity to address various types of viral threats—not just acute challenges. “One of the largest opportunities for these compounds is hepatitis B in both the developed and the developing worlds,” says Iodonato. This focus makes sense, considering that 240 million people worldwide are infected with the hepatitis B virus (HBV), and 600,000 people per year die as a result.
Averting catastrophe before it happens
The Ebola crisis was a tipping point, because it allowed companies that were already in the early stages of innovative R&D, focused on new types of infectious disease drugs, to gain momentum. And hopefully, all of this hard work and heightened awareness will leave us better-prepared for the next epidemic or pandemic crisis.