On September 18, Sarepta Therapeutics [Nasdaq: SRPT] announced the company’s lead therapeutic drugs for Ebola Virus and Marburg Virus had been granted Fast Track Designation status by the FDA. The company’s AVI-7288 and AVI-7537, for the treatment of Marburg Virus and Ebola Virus respectively, remain in clinical development. The company plans to initiate a Phase I for AVI-7288, which is currently in studies under a Department of Defense contract.
Fast Track Designation drugs qualify for qualify for the expedited process Priority Review, which is granted to therapies operating in areas of significant unmet medical need.
In July, AVI BioPharma renamed itself Sarepta Therapeutics and announced a one for six reverse stock split. The company develops first-in-class RNA-based therapeutics based on a platform technology which can target both messenger RNA and precursor messenger RNA, allowing for a number of diverse therapeutic applications.
The company’s lead candidate, eteplirsen, in development for Duchenne muscular dystrophy, and its pipeline consists of other infectious diseases. This announcement was highly anticipated by investors and insiders, which caps a busy summer for the Cambridge-based company. In July, Eteplirsen achieved significant clinical benefit on its primary clinical outcome — a six-minute walking test — in the company’s Phase II study. On the release date of this data, the stock spiked 146 percent to $8.52. The stock has continued to climb, and in early September announced an at-the-market offering with Citadel worth up to $40MM. The stock currently trades at around $16.00.
Despite the promise of this and other technologies in clinical development, the federal government issued a stop work order for Sarepta and Tekmira Pharmaceuticals in August. The two companies have received lucrative defense contracts to enter clinical phase, now threatened as the government assesses budgets and possible termination of the program.
Sarepta was awarded a four-phase contract in July 2010 worth $80 million in the initial phase of R&D funding that would have stretched into mid-2013. Further extensions of this contract could have led to $291 million in funding. The stop work order, ordered on August 2, endangers $145 million, about half of the contract. Despite receiving Fast Track Designation for the drugs, as of September 21 the stop work order remains in place.
Tekmira Pharmaceuticals — another DoD-sponsored company developing a treatment for Ebola an Marburg — disclosed on August 6 that it had received a temporary stop work order. The company was in the middle of a phase 1 dosing trial. In a press release issued August 31, Tekmira said it expects the DoD to make a decision by September 30.
In April, OneMedPlace identified several smaller, microcap and nanocap companies with impressive technology and potential to do significant damage in this space. Sarepta — then AVI BioPharma — and Tekmira made the list as one of the companies ready to skyrocket. OneMedPlace will continue to watch these stop work orders, which can be potentially catastrophic for these two companies — as well as the entire sector.
To the scientific community, the Ebola virus is one of the most noxious pathogens identified to date. To the general population, the virus is dreadful, made especially frightening in pop culture.
In addition to a high mortality rate of approximately 70 percent per case (average)1, the health deterioration caused by an Ebola infection is especially poignant. Infection by this RNA virus – a member of the Filovirdae virus family that also includes Marburg – is consistent with labored breathing, muscle and joint pain, diarrhea, vomiting, seizures, fever, edema, conjunctivitis, skin rashes, and hematomas. Approximately 10 percent of Ebola cases cause severe internal and external hemorrhaging that includes bleeding from the intestine, nose and mouth2-4. Ultimately, multiple-organ dysfunction ensues and causes death.
Currently, there are no FDA approved vaccines or treatments for Ebola3,5. Patients are essentially treated with palliative measures that include antibiotics for secondary infections, fluid and electrolyte supplementation to prevent dehydration, oxygen administration to aide breathing, and pro-coagulants to aid in controlling hemorrhaging. Taken together, the severity of Ebola infections and the lack of Ebola-specific treatments make it both critical and challenging to develop successful therapies, currently an unmet medical need. In this article we feature three companies that are making significant strides in actualizing successful treatment regimens for Ebola infections.
AVI BioPharma (now Sarepta Therapeutics) has developed a leading-edge technological platform for the modulation of genetic expression in the treatment of diseases. At the core of the company’s innovations are novel modifications to the chemical structure of RNA, the polymeric molecule that is differentially expressed in unique cell types of different tissue (i.e. heart vs. brain). Using this technology, the company has developed a diverse product pipeline of therapeutic RNA oligomers. Unlike other conventional RNA-based compounds, Sarepta’s therapeutics have enhanced efficacy and stability, improved safety profile, expanded flexibility for specified targeting to different organs, and can both down-regulate or up-regulate gene expression.
Specifically, the company has developed its lead candidates AVI-6002 and AVI-6003 (renamed AVI-7537 and AVI-7288) for the treatment of Ebola and Marburg viruses, respectively. Both of these products function by distinctly suppressing the genetic expression of the viral genome, thereby stopping their proliferation. The company has shown in preclinical trials that the two drugs reproducibly achieve high survival rates of 80% in AVI-7537 and 100% in AVI-7288 in non-primate animals that have been challenged with lethal infections of Ebola and Marburg viruses.
Sarepta’s lead candidate is a splice switching oligomer for Duchenne Muscular Dystrophy, currently in Phase II. In addition, the company is in pre-clinical stages for treatments of hemorrhagic virus infections and influenza.
NanoViricides Inc. has developed a powerful, adaptive technological platform with design capabilities that enables the effective treatment of a viral infection as needed. The central component of the company’s technology is a nano-particle termed nanoviricide, which is comprised of a micelle polymer containing disease-specific ligands that are recognized by the particular virus being targeted. Functionally, the virus recognizes and binds the nanoviricide’s ligand, at which point the nanoviricide engulfs the viral particle causing it to lose its viral coat proteins, effectively neutralizing the virus and rendering it unable to cause any further infection. Unlike other methodologies that aim to bind and neutralize a virus, such as antibodies, the nanoviricide is able to neutralize the virus without the added help of the immune system, providing a much more direct and simplified modality of treatment. Each nanoviricide can be specifically tailored to a virus by simply changing the ligand component, making this platform highly adaptable and wide reaching.
NanoViricides is currently developing its technology for the treatment of Ebola/Marburg virus under its bio-defense program. The ability of the company to stock-pile basic-form nanoviricides that can be quickly up-scaled to target a specific virus poises this platform as a highly promising treatment in the case of an alarming epidemic, as can occur with Ebola. In such an instance, the company would quickly manufacture the nanoviricide with the ligands for the specific Ebola or Marburg virus outbreak, even if it were a new strain of the virus, thereby serving to control the spread of the epidemic. This area of the company’s pipeline is currently in pre-clinical animal studies analyzing efficacy, and the company aims to obtain non-equity funding for this important bio-defense sector.
**Listen to the OneMedRadio interview with NanoViricides CEO Eugene Seymour.**
Tekmira Pharmaceuticals is an emerging biotechnology company that has developed an innovative technological platform to potently down-regulate genetic expression indicated for the treatment of diseases. At the foundation of the company’s platform is a breakthrough drug delivery technology termed LNP (lipid nano-particle), which is comprised of lipid molecules structured in a circular bi-layer that serve to encapsulate therapies and significantly improve drug stability, safety, and bioavailability in the blood stream. The company is using its LNP technology to deliver advanced therapeutic RNA oligomers (multivalent siRNA) that can significantly inhibit gene expression, but are limited by instability in the body. Tekmira has shown in preclinical trials that systemic administration of siRNA using LNPs effectively delivers drugs to target organs, achieving levels of gene suppression that were not previously possible using siRNA alone.
Tekmira’s lead candidate, TKM-Ebola, utilizes LNP/siRNA in conjunction to suppress the expression of the Ebola viral genome, thereby stopping the progression of Ebola infections. In pre-clinical trials using non-human primates, Tekmira showed that TKM-Ebola was able to provide complete protection to animals that were subjected to lethal doses of the Ebola virus.
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2. Kortepeter MG, Bausch DG, Bray M. Basic clinical and laboratory features of filoviral hemorrhagic fever. J Infect Dis. 2001 Nov;204 Suppl 3:S810-6.
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4. Mupapa K, Massamba M, Kibadi K, et al. Treatment of Ebola hemorrhagic fever with blood transfusions from convalescent patients. International Scientific and Technical Committee. J Infect Dis. 1999 Feb;179 Suppl 1:S18-23.
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