NEW YORK (GenomeWeb) – CalImmune this week announced that it has been cleared by the US Food and Drug Administration to treat a second cohort of patients in a clinical trial of its expressed RNAi-based treatment for HIV infection.
The ruling comes after the firm's data safety monitoring board (DSMB) determined that none of the patients treated in the trial thus far experienced any serious adverse events, CalImmune said.
"This recommendation from the DSMB is an important step in bringing this potential one-time therapy to the patients, and takes us closer to our ultimate goal of eradicating AIDS," CalImmune CEO Louis Breton said in a statement.
CalImmune was founded to develop a method for preventing HIV infection from progressing to AIDS by knocking down CCR5, a chemokine receptor used by HIV as a co-receptor in order to infect cells. The approach is based on the discovery in the 1990s of a small population that did not contract HIV despite repeated exposure to the virus due to a lack of CCR5 on the surface of their T cells.
Later research identified a heterozygous population with approximately half the amount of CCR5 on the surface of their T cells was found to be susceptible to HIV infection, but experienced a delay in progression of the disease between three and five years.
CalImmune's therapy, called Cal-1 (formerly CAL-USA-11), involves isolating a patient's T cells and stem cells from peripheral blood, then treating them with a lentiviral vector containing CCR5-targeting shRNAs and an agent designed to prevent fusion of the virus with host cells. The cells are then re-infused during an out-patient procedure. Delivering the agent to T cells is expected to provide immediate protection to a patient, while delivery to stem cells will offer long-term protection.
About a year ago, CalImmune kicked off a Phase I/II study, enrolling four HIV-infected individuals who had received antiretroviral therapy but stopped treatment due to concerns over toxicities or treatment fatigue. Breton noted that this is the initial target population for Cal-1, representing nearly 6 million patients worldwide.
These individuals were treated with Cal-1 alone, then monitored for adverse reactions. With none observed, CalImmune is now cleared to move into the next four-patient cohort, who will receive Cal-1 after preconditioning with four mg/kg of busulfan, a chemotherapeutic that aids cell engraftment.
"We needed to make sure that we established the safety profile of Cal-1 and do that without any additional therapeutic," Breton told Gene Silencing News. "We believe we have taken that first step."
The trial is also designed to enroll a third four-patient cohort, which will receive two four mg/kg doses of busulfan prior to Cal-1 treatment, but Breton said that CalImmune may skip this step and move directly into a pivotal study depending on data from the second cohort.
In either case, the company anticipates completing the Phase I/II trial before the end of 2015.
As development of Cal-1 continues, CalImmune is also working on a number of other RNAi-based drugs that Breton said include both ex vivo and in vivo routes of administration. However, he declined to provide specific details about these efforts.
He did note that CalImmune expects to advance these earlier-stage programs in collaboration with industry partners.