Gammora, an investigational medicinal product (IMP), was tested in a first-in-human (FIH) clinical trial for HIV. The IMP is a synthetic peptide compound derived from the HIV enzyme integrase and is formulated as a sterile, isotonic and non-pyrogenic solution for subcutaneous administration, according to Zion Medical.
PolyPeptide Labs, a contract manufacturing and development organization (CDMO), manufactures the drug at its California plant.
Read more: FDA publishes guidance on expansion cohort use in FIH clinical trials
Esmira Naftali, chief operation and development officer at Zion Medical, told us that integrase is an enzyme that inserts the virus’ genetic material into the DNA of the infected cell. Gammora works to integrate HIV DNA fragments into the host cell’s genomic DNA and stimulates “self-destruction” of the infected cell, she explained.
Gammora’s mechanism of action was demonstrated in preclinical models using isolated patient-derived lymphocytes, Naftali told us. Through in vitro studies, the company reported that the efficacy of the peptide significantly reduced the viral load in patient-derived HIV-infected lymphocytes.
Zion conducted a Phase I/IIa human clinical trial, which, according to the company, showed safety and efficacy of the drug in its ability to ‘kill’ HIV-infected cells.
The company collaborated with the contract research organization (CRO) Gsap to develop a clinical protocol, though the entire clinical study was conducted under the responsibility, sponsorship, and supervision of Zion Medical.
Zion hopes to initiate a Phase IIb in the coming months, involving approximately 50 patients given Gammora over two to three months.
Clinical trial shows drop in viral load
Nine HIV-positive patients enrolled in the trial conducted at the Dr. Ronald Bata Memorial Hospital in Uganda, in which the patients showed a reduction of the viral load of up to 90% from the baseline load.
Patients were then given the IMP with additional antiretroviral treatment for another five weeks twice a week, in a Phase II study. The results found that combined-treatment patients sustained a viral suppression of up to 99% reduction in viral load from baseline.
The trial demonstrated that the IMP was safe and tolerable, according to the company. Patients showed an increase of CD4 cell count, or T cells, of up to 94% from baseline. In both preclinical and early clinical studies, Gammora’s treatment mechanism of reducing viral load in infected cells was successful.
Naftali explained that even once there is an undetected level of viral load in the plasma, infected cells still remain. An undetected viral load is known as a functional cure for HIV. Most antiretroviral therapies can produce a functional cure in HIV patients. However, Naftali believes that “Gammora can affect those cells [remaining infected cells] too.”
Zion in-licensed the compound and has continued research and development through preclinical and clinical stages. The company has filed a patent application for an updated version of the peptide and final drug composition.
Correction: A previous version of this article incorrectly said that Gsap conducted the first-in-human clinical trial. The CRO was contracted by Zion but did not participate in or administer the human clinical trial in Uganda. Gsap has not responded to a request for comment.