First HIV mAb ibalizumab hits PhIII target

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Canadian specialty pharma Theratechnologies and its biotech partner TaiMed Biologics have posted positive top-line results for the first-ever antibody HIV treatment.

Ibalizumab hit its primary end point in a Phase III trial in patients with multidrug-resistant HIV-1.

Preliminary results released from the companies show that 82.5% of patients enrolled in the TMB-301 study (33 out of 40 patients) have met the primary endpoint of a decrease of ≥ 0.5 log10 in viral load following a 7-day treatment period with ibalizumab, a CD4-directed HIV entry-inhibitor

This result is statistically significantly better than results observed during the control period, according to the biotech, which added that the drug was well tolerated during the first week of treatment. TaiMed said it plans to submit an abstract to present these results at a “major scientific conference” later this year.

Antibodies work through a mechanism that is distinct from that of traditional antiretroviral therapies--which are the standard treatment for HIV--as they directly target free virus as well as virally infected cells, whereas existing antiretroviral drugs only inhibit the replicating virus.

Although highly effective in the majority of patients, current antiretroviral therapies are limited by toxicities and resistance, and are unable to cure HIV infection.

The two partners are betting that this could offer a new strategy. Although it has not been tested in this trial, there is also scope for antibodies to be used alongside antiretroviral therapies.

Dr Jay Lalezari, medical director of Quest Research and principal investigator of the TMB-301 clinical trial, said: “We are excited by these results. Ibalizumab is the first monoclonal antibody for the treatment of HIV to reach Phase III and these primary endpoint results indicate that we are moving closer to providing a new treatment option for HIV patients with very limited alternatives.”

This study is the last trial required by the FDA to complete the Biologics Licence Application (BLA) submission. The 24-week treatment study is still underway and the companies said it should be completed before the end of October 2016, and they expect to apply for approval next year.

Luc Tanguay, president and CEO of Theratechnologies, said: “Ibalizumab continues to perform well in clinical trials, both in terms of safety and efficacy. We are actively collaborating with our partner, TaiMed, to ensure that all activities related to the BLA will be completed in due time. We have also recently initiated activities to support the successful launch of ibalizumab in the U.S, if approved by the Food and Drug Administration.”

In March the two companies signed a 12-year collab to market and distribute ibalizumab in North America. It has already gained a "Breakthrough Therapy" by the FDA, as well as Orphan status, based on preliminary clinical evidence indicating that it may represent a substantial improvement over existing therapies on one or more clinically significant endpoints.

In a previous Phase IIb clinical trial, conducted on 113 patients, the product significantly reduced viral load in multi-drug resistant HIV-infected patients.

TMB-301 is a single arm, 24-week study of ibalizumab plus optimized background regimen (OBR) in treatment experienced patients infected with multi-drug resistant HIV-1.

The primary objective of the study is to demonstrate the antiviral activity of ibalizumab 7 days after the first dose of ibalizumab. Patients receiving their current failing ART regimens were monitored during a 7-day control period.

Thereafter, a loading dose of 2,000mg of intravenous ibalizumab was the only ART added to their regimen. The primary efficacy endpoint is the proportion of patients achieving a ≥ 0.5 log10 decrease in HIV-1 RNA 7 days after initiating Ibalizumab therapy, day 14 of the study. Ibalizumab is continued at doses of 800mg IV every two weeks through 24 weeks on study treatment. Safety and additional efficacy endpoints are also evaluated during the study.

Ibalizumab is currently administered as a bi-monthly intravenous injection. TaiMed is conducting clinical trials with the same formulation for bi-monthly intramuscular injection (IM) and monthly IM administration. Theratechnologies has exclusive rights to market and distribute the drug for the IM route of administration.

Under the deal, Theratechnologies has exclusive rights to commercialize ibalizumab in the U.S. and in Canada. TaiMed will continue to be responsible for development of ibalizumab and seek approval from the FDA, whereas Theratechnologies will be responsible to obtain the approval from Health Canada.

TaiMed will manufacture and supply ibalizumab to Theratechnologies at a transfer price of 52% of net sales of the product.

This builds on preclinical work on using mAbs for the disease, with a paper published in Nature back in 2013 showing antibody treatments resulted in a “rapid and precipitous decline of virus in both blood and tissues of the infected monkeys.”

Following a single antibody infusion, viral loads dropped sharply to undetectable levels in three to seven days, and cell-associated virus levels were also reduced in the blood, lymph nodes and the gut. Moreover, antibody infusions significantly boosted the monkeys’ own immune responses against the virus, which appeared to have long-term benefit, the authors from the Beth Israel Deaconess Medical Center found.

Ibalizumab is the most advanced mAb in testing, but there are other candidates undergoing trials--including VRC01, which late last year showed in a small, early-stage trial that it was safe and temporarily decreased the level of virus in the people who were not receiving anti-retroviral therapy.

VRCO1 was created by scientists from the U.S. National Institute of Allergy and Infectious Diseases.

-check out the release

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