NEW YORK (GenomeWeb) – Tekmira Pharmaceuticals may not be able to meet its year-end goal of providing US regulators with the data required to lift a hold on a Phase I trial of its investigational Ebola therapy TKM-Ebola, company officials disclosed last week.
Instead, the company is focusing its efforts on a version of the drug specifically designed for the strain of the virus causing the outbreak in West Africa.
"The current outbreak is being driven by [the] Guinea" strain of the Ebola virus, Tekmira President and CEO Mark Murray said last week during a conference call held to discuss Tekmira's third-quarter financial results. "So we are focused on [a Guinea-targeting] product and collecting data with that product."
Given the urgency of the current Ebola outbreak, pushing forward with the healthy volunteer trial of TKM-Ebola "is just not terribly meaningful at this moment," he added.
TKM-Ebola combines Tekmira's proprietary lipid nanoparticle delivery technology with siRNAs against three targets in the Zaire strain of the Ebola virus. It is being developed with the support of a US Department of Defense contract worth up to $140 million.
After dropping a first-generation version of the drug to focus on a version of the drug that uses an improved lipid nanoparticle formulation, Tekmira moved TKM-Ebola into a Phase I trial that would test single and then multiple ascending doses of the agent in healthy individuals.
Data from the first arm of that trial showed TKM-Ebola was well tolerated at doses up to .3 mg/kg, but there were still adverse events observed at all dose levels. Notably, the therapy does not involve the use of pre-mediation to address immune responses associated with siRNAs.
This summer, the US Food and Drug Administration halted the study before the multiple dose portion got underway, ordering Tekmira to provide additional data related to the cytokine release observed in those receiving higher doses of the drug in the first part of the trial.
Murray had previously stated that Tekmira was making changes to the study's protocols and preparing the requested data so that it could move forward with the Phase I trial, and that the regulatory issues were likely to be resolved before the end of this year.
However, a number of developments have led Tekmira to back away from that guidance.
"Early this quarter the genetic sequence of the Ebola virus Guinea strain became available," Murray noted during last week's call. "With this sequence information we designed a new RNAi therapeutic, which we call TKM-Ebola-Guinea, specifically targeting the Guinea strain."
Manufacturing of that drug has begun and supplies will be available by early December, he said. Additionally, the DoD has exercised an option in its agreement with Tekmira to obtain roughly 500 treatment courses of TKM-Ebola-Guinea, which is valued at $7 million.
Meanwhile, TKM-Ebola has been provided to "several" patients with confirmed or suspected Ebola virus infection under an expanded access exemption from the FDA. In order to preserve patient privacy, the individuals receiving the drug are not being disclosed. However, Tekmira Chief Discovery Officer Michael Abrams said during the call that these patients are "primarily in the US."
As a result, "the clinical development pathways for our Ebola products have evolved and may continue to evolve," Murray said. "So we may not resolve the partial clinical hold of the healthy volunteer multiple ascending dose portion of the Phase I trial of TKM-Ebola of this year.
"It’s really a question of focus and potential relevance," he continued. "We're focused now … on evaluating the products in true patients and there is less need to evaluate the material in healthy volunteer subjects."
For the three-month period ended Sept. 30, Tekmira's net loss rose to $8.6 million, or $.39 a share, from $5.9 million, or $.41 a share, the year before.
Revenues in the quarter rose to $4.4 million from $3 million, reflecting the recognition of $1.6 million in deferred revenues from partner Bristol-Myers Squibb. With the expiration of that arrangement, Tekmira released the deferred revenue.
Research and development spending, as well as collaboration and contract costs, totaled $9.3 million in the third quarter, compared with $5.5 million a year earlier. General and administrative costs rose to $1.8 million from $1 million.
At the end of the third quarter, Tekmira had cash, cash equivalents, and total securities worth $120.5 million.