Pharma & Healthcare 9/22/2014 @ 4:23午後 2,045 views
Tekmira Tempers FDA OK For Ebola Drug Access
Tekmira Pharmaceuticals announced today that the US FDA and Health Canada have agreed to a “regulatory framework and treatment protocol” that will permit their Ebola drug, TKM-Ebola, to be used in infected patients under the terms of extended access, known more commonly as “compassionate use.”
This news follows on an announcement Friday by French Minister of Social Affairs, Health, and Women’s Rights, Marisol Touraine, that “exceptionally” authorizes the use of experimental drugs from Tekmira and others on a French nurse who contracted Ebola.
The young woman had been volunteering for the medical humanitarian organization, Médecins Sans Frontières (MSF), and was transported overnight Friday from Liberia to a military hospital outside Paris.
In addition to Tekmira’s TKM-Ebola (also known as TKM-100-802), she is authorized to receive MediVector’s broad-spectrum antiviral, favipiravir (T-705), and ZMapp, the three-antibody cocktail for which supplies are reportedly exhausted.
CEO tempers expectations
In announcing that the company had already supplied the drug to some patients under emergency protocols, Tekmira President and CEO, Mark J. Murray, PhD, said in a company press release, “We have insisted on acting responsibly in the interest of patients and our stakeholders.”
But Murray cautioned:
“However, it must be kept in mind that any uses of the product under expanded access, does not constitute controlled clinical trials. These patients may be infected with a strain of Ebola virus which has emerged subsequent to the strain that our product is directed against, and physicians treating these patients may use more than one therapeutic intervention in an effort to achieve the best outcome.”
I cannot stress enough the importance of Dr. Murray’s statement.
Why, and what is TKM-Ebola anyway?
TKM-Ebola is a collection of three, small interfering RNA molecules (siRNAs) packaged into their proprietary lipid nanoparticle technology (LNP).
These siRNAs are targeted to cause the destruction of messages for three Ebola virus proteins: the virus L polymerase, VP24 and VP35. However, the precise code they’re directed against are derived from the 1976 Mayinga strain of Ebola virus Zaire, not the currently circulating strain in west Africa. (Mayinga N’Seka was a nurse infected in the first documented Ebola outbreak. For more technical readers, TKM-Ebola is directed again polymerase L (EK-1 mod), VP24 (VP24-1160 mod), and VP35 (VP35-855 mod)).
The highly-touted 2010 Lancet study led by UT-Galveston’s Thomas W. Geisbert, PhD, where what is now TKM-Ebola provided “100%” protection of monkeys (4 out of 4 monkeys, vs. one control that died) was against a challenge from the 1995 Kikwit strain of Ebola Zaire. On one hand, this shows that TKM-Ebola could be effective against a strain separated by almost 20 years, but is no guarantee that it will against the currently-circulating strain.
This 1976 photograph shows two nurses standing in front of Kinshasa case #3 (Nurse Mayinga N'Seka) who was treated and later died in Ngaliema Hospital, in Kinshasa, Zaïre. Credit: CDC/Dr. Lyle Conrad
This 1976 photograph shows two nurses standing in front of Kinshasa case #3 (Nurse Mayinga N’Seka) who was treated and later died in Ngaliema Hospital, in Kinshasa, Zaïre (now Democratic Republic of Congo). Credit: CDC/Dr. Lyle Conrad
Moreover, it’s not clear what interpretable data will be gained from expanded access to this drug. As Murray state, this is not a formal clinical trial. That means that the drug can be offered to patients without the typical stringent disease-staging definitions and other qualifications that aim to eliminate confounding factors in a formal trial.
We also don’t know precisely how much TKM-Ebola the company has on hand, or can produce and finish quickly. Therefore, the number of patients that could be treated might not be powered sufficiently to compare to a untreated control group (or what control group the results would be compared against).
And while I’m suggesting caution, others are somewhat more cynical. Twitter user Medical Skeptic (@medskep) wrote of the Tekmira announcement, “It’s throwing spagetti against the wall time.”
As the markets closed today, Tekmira traded up 17.1% on the NYSE and 14.9% on the Toronto Stock Exchange.
http://www.forbes.com/sites/davidkroll/2014/09/22/tekmira-tempers-fda-ok-for-ebola-drug-access/
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