GlaxoSmithKline, Amgen Inc. lead race for Ebola drugs
Ken Odeluga October 29, 2014 8:53 PM
<p>12,000 suspected Ebola cases have resulted in almost 5,000 deaths to date, in the most extensive outbreak of the disease ever seen. Ebola virus disease, […]</p>
12,000 suspected Ebola cases have resulted in almost 5,000 deaths to date, in the most extensive outbreak of the disease ever seen.
Ebola virus disease, or simply Ebola, is a disease of humans and other primates.
The potential causes and symptoms have been well reported elsewhere, with the UN’s health agency, the World Health Organisation, stating that the outbreak is amongst the “most challenging” for health workers since the deadly disease emerged in Africa four decades ago.
The international health body later declared an ‘International Public Health Emergency’ in relation to the Ebola outbreak in West Africa.
Additionally, it’s arguable the outbreak, concentrated in Africa, but also sporadically appearing in the West, has had a chilling albeit ambiguous effect on financial markets.
However, what we’d like to focus on here is a burgeoning industry of pharmaceutical firms that have joined the fight against the disease.
Whilst it will take more than the commercial imperative to bring the current outbreak under control and in time, stamp out the disease entirely, drug development will inevitably play a big part, and the parties that meet the earliest success will be lauded by both the wider public and investors.
And it almost goes without saying that the ‘race’ to find treatments is not solely a rush to try to preserve life, but also a race for profit.
All Ebola treatments are experimental
It’s worth stressing that all the medicines mentioned in this article would be classified as experimental and many have been ‘fast-tracked’ by regulatory authorities.
Progress along the road of clinical trialling differs, but few of the compounds listed below would have been likely to come to the market for routine use even within the next few years, under normal circumstances.
Their potential use would be dependent on the discretion of regional regulators and official approval would probably be on an ad hoc basis, if at all.
The WHO published a report on the ethics of using unregistered interventions to treat Ebola in which it concluded: “In the particular context of the current Ebola outbreak in West Africa, it is ethically acceptable to offer unproven interventions that have shown promising results in the laboratory and in animal models but have not yet been evaluated for safety and efficacy in humans as potential treatment or prevention.”
Favipiravir, or T-705 or Avigan: an experimental anti-viral drug being developed by, Toyama Chemical Co., a subsidiary of Tokyo-listed Fujifilm Holdings Corp.
Prospects for the drug against Ebola appear in the balance so far.
It was originally developed as an antiviral against influenza, West Nile Virus, yellow fever, foot-and-mouth disease and other diseases.
Some effectiveness at extending life was reported against Ebola-infected mice, though no mice ultimately survived.
There is a report that a nurse who contracted Ebola whilst working for Médecins Sans Frontières in Liberia recovered after being administered the drug.
Senior researchers on the development programme have stated administration should start no later than the day of onset to increase the chances of success.
This is an antiviral of the drug class known as adenosine analogues. It’s being developed by Nasdaq-listed BioCryst Pharmaceuticals Inc.
It was initially targeted at Hepatitis C, but has more recently been developed as a possible treatment of filovirus infections like Ebola.
The compound is said to work by blocking the reproduction of the virus inside infected cells.
However, it appears that even under Federal Drug Administration (FDA) ‘fast-track’ approval status, the drug might not be available for use as a treatment of humans until the end of 2016.
This is an experimental antiviral from Nasdaq-listed Chimerix Inc. A ‘prodrug’ (less potent version) of a compound called Cidofovir, the latter primarily used as a treatment for retina infections in people with AIDS.
Brincidofovir is another intracellular treatment against viruses made up of DNA material. Purely clinical tests, i.e., In Vitro—without humans or animals, have suggested its potential as a treatment of Ebola virus.
Scientists deem its potential as surprising, as Ebola is not a DNA virus.
Even so, Chimerix this month received FDA authorization for emergency investigative new drug applications of brincidofovir, for the treatment of Ebola virus disease.
Last week, Chimerix claimed it had approval to commence Phase II trials in Ebola infected patients, noting tablets of the drug are now available for immediate use in clinical trials.
GlaxoSmithKline Plc. is marketing this treatment under the brand names Zeffix, Heptovir, Epivir, and Epivir-HBV as a treatment of chronic hepatitis B.
Initially developed by researchers at Emory and Yale Universities in the late 80s, positive results were reported, in September 2014, by a physician, in 15 patients with Ebola in Liberia.
13 of the patients were treated within three-to-five days of observed symptoms and survived. The other two patients, treated after more than five days of displaying symptoms, died.
Researchers at the US’s National Institute of Health (NIH) expressed doubt about the results, noting In Vitro tests were negative. The NIH has said it will continue to research the use of Lamivudine against Ebola.
A ‘broad-spectrum’ antiviral jointly developed by China’s Academy of Military Medical Sciences and Sihuan Pharmaceutical Holdings Group Ltd, whose stock is listed on the Hong Kong exchange.
In tests on mice it is claimed JK-05 showed efficacy against RNA viruses, including influenza, Ebola virus and yellow fever.
There is some controversy clouding the potential widespread use of the drug against Ebola because
- The chemical structure of the product hasn’t been publicly disclosed
- China has only given limited approval for its use: preliminary approval has been granted for use by Chinese workers involved in treating patients during the current outbreak.
Even so, it’s thought this simple ‘small molecule’ drug would readily lend itself to mass production if on-going tests prove successful.
Antisense therapies seek to utilise nucleic material (DNA, RNA) in the combat of diseases. These strands attach themselves to other genetic material in a way which can inactivate or modify the effect of other genetic material.
Sarepta Therapeutics Inc., listed on Nasdaq, appears to be only one of two companies developing an Ebola medicine in this category.
The Cambridge, Massachusetts based company has been somewhat overlooked by authorities that might have been able to expedite its antisense technology-based drug, but the firm has had to repeatedly remind authorities during the summer that its drug, AVI-7537, was available in limited quantities.
The US government in years past funded Sarepta’s research on Ebola, until the Department of Defense cut the program for budgetary reasons in 2012.
In mid-October 2014, Sarepta issued a press release announcing the anticipated publication of a study showing “no clinical or toxicologic safety concerns” in human test subjects administered AVI-7537.
Tekmira Pharmaceuticals Corp. is conducting Phase I clinical trials of TKM-Ebola.
However, the British Columbia, Canada-based company has had a very chequered recent history with US health regulators over TKM.
The FDA brought the development of the medicine to a standstill in July after it was tested on only a handful of people, amid safety concerns over the highest doses, following a number of problematic immune responses.
Early in August, US authorities said Tekmira could resume testing the drug in people infected with Ebola, relaxing its stance, somewhat.
The company acknowledged in recent weeks TKM-Ebola remained on partial clinical FDA ‘hold’, with respect to multiple ascending dosing in healthy subjects. But Tekmira said it expected “this matter to be resolved this quarter.”
TKM-Ebola is one of only two drugs the FDA has allowed to be used in Americans who had contracted Ebola virus disease.
The other is ZMapp.
The only monoclonal antibody vaccine (made up of identical immune cells) to have been tested against Ebola virus disease.
It is also one of the few drugs to be specifically developed for Ebola.
Even so, in scientific terms, there is no proof that it is an effective treatment. Because of current limited supply, only a small number of Ebola patients have been treated with the drug. Some survived, but more trials are deemed necessary before efficacy and safety can be assumed.
US pharmaceutical giant Amgen Inc. has this month received funding and assistance from the US Department of Health, the Bill & Melinda Gates Foundation and other groups, to see whether large scale production is possible.
This has produced much publicity for the firm and for the drug which may not be warranted, given the uncertainty surrounding ZMapp’s effectiveness in curing Ebola.
The biopharmaceutical was initially developed by Leaf Biopharmaceutical Inc.,a unit of San Diego, California-based Mapp BioPharmaceutical. Leaf partnered with Canadian Defyrus Inc.
None of the firms are listed; each reportedly developed differing proprietary combinations of antibodies.
Blood serum from Ebola survivors is considered a promising development path to explore for the treatment. During a recent meeting convened by the World Health Organisation, authorities deemed this line of research a top priority. However, development of this type of therapy is at a much earlier stage than antiviral treatment therapies.
Many vaccines with potential for use against Ebola have been developed over the past decade, but few have been developed enough to reach the stage at which they may be trialled in human beings.
None have yet been approved by the US’s FDA for clinical human use.
There are a number of promising candidates (some have protected primates against infection) but human testing has run up against the fundamental ethical issue.
This has given rise to the FDA’s “animal rule”: in special cases, animal studies may, in combination with evidence of safety and immune response data from humans given the vaccine, replace trials involving deliberate infection of humans.
The primary experimental vaccine protection against Ebola currently under development. Phase I trials began in September.
GlaxoSmithKline took over development of the drug, jointly with the US National Institute of Allergy and Infectious Diseases, after buying the NIAID’s original commercial partner, Okairos AG, in May 2013.
GSK is now the only major pharmaceutical company developing more than one potential type of Ebola drug that has progressed to clinical trial stage.
GSK has estimated it might be able to make about 1 million doses of vaccine a month by December 2015.
The GSK vaccine is already undergoing safety tests in Britain, US and Mali.
Another potential vaccine to prevent Ebola. It was initially developed by the Canadian National Microbiology Laboratory.
The vaccine was created by combining a bovine flu-like stomach virus with an Ebola gene.
It was licensed to NewLink Genetics Inc., a small-cap cancer drug company based in Ames, Iowa, with just 120 employees.
However, Canadian authorities in partnership with an agency of the US Dept. of Defense are also continuing to research use of the vaccine.
Following a well-publicised meeting with WHO on 23rd October, it emerged NewLink could have, under a best-case scenario, as many as 12 million doses of its experimental vaccine by April 2015. That number would far outstrip GSK’s estimate of 230,000 doses by that date.
Caveats include the fact that NewLink’s vaccine requires a high dose to be effective, meaning the rate of potential immunisations would be lower compared with other potential treatments.
The University Hospital of Geneva will soon begin testing the NewLink Genetics vaccine on a similar number of volunteers as the GSK vaccine study.
Results from both of these and other early trials will provide the basis for planning larger studies, involving thousands of participants, and for choosing vaccine dose-level for such efficacy trials.
More distant prospects
Aside from the major antiviral candidates outlined above, there are a number of more distant prospects under development.
The Health Ministry of Russia said it developed a vaccine called Triazoverin that is effective against Ebola. The treatment may be available for clinical trials in West Africa as soon as the start of 2015.
A few days ago, Novavax Inc., a $1.3bn biopharmaceutical company listed on Nasdaq, said an Ebola virus vaccine using recombinant technology (DNA engineering) would be developed in a “few weeks”.
Novavax said “preclinical models” demonstrated an immune response that could be further enhanced if treatment was combined with Novavax’s “Matrix-M”, a wide-spectrum immunotherapy.
This particular vaccine therapy has drawn wide interest among medical experts given it does not need to be frozen and seems to be suitable for rapid scaling to manufacture large quantities of doses.
However, it’s not clear how soon Novavax’s EBOV GP will progress beyond the non-human primate stage studies.
In September, Hemispherx Biopharma Inc., a small firm with a New York Stock Exchange listing, said it struck an agreement with the US Defense Dept.’s Medical Research Institute of Infectious Diseases (USAMRIID), to test Alferon N and Ampligen against the deadly Ebola virus.
Alferon N is an alpha interferon (natural defensive protein) commercially approved in the US for genital warts and Ampligen is an immune therapy drug, initially intended for illnesses like AIDS.
Bavarian Nordic A/S, early in September announced it would “accelerate its collaboration” with the US NIAID for development of Ebola vaccine programs.
The Denmark-headquartered firm, whose stock is listed on the Copenhagen exchange, said it and its partners were planning to initiate the first trial of a promising combination vaccine in humans in 2015.
Ebola drugs developed by group would be based on Bavarian’s MVA-BN combined vaccine against Ebola and Marburg, which it has been working to advance for “several years”.
A recent study, conducted under NIAID’s vaccine preclinical services program, demonstrated “proof of concept” of two vaccines based on MVA-BN technology and another based on a Johnson & Johnson Inc.-manufactured product called AdVac.
It could also have been useful to assess companies which make products aside from drugs that could be used in the treatment of Ebola, to maintain safety of healthcare workers and prevent further infection.
‘Hazmat’ suit makers like Azearth Corp. would fall into this list, as would UK mid-cap stock Synergy Health Plc., a firm involved in specialised outsourced healthcare services, medical device sterilisation and hospital sterilisation.
For the sake of a basic performance comparison, we have charted some of the stocks we mentioned below.
Each stock price series has been re-based to zero to make visual assessment easier.
SRPT Sarepta Inc.
GSK.L GlaxoSmithKline Plc.
BCRX BioCryst Pharmaceuticals Inc.
CMRX Chimerix Inc.
NVAX Novavax Inc.
HEB Hemispherx Biopharma Inc.
4901.T Fujifilm Holdings Corp.