UK approves Ab trial for HIV/AIDS
arena after UK authorities gave the go ahead to commence the
company's first clinical trial of its human antibody to treat the
virus.
There is a certain degree of expectation attached to this latest treatment as scientists have intentionally targeted a protein that means chances of resistance to the treatment are reduced. The development of resistance is a major problem with all currently available HIV/AIDS treatments. HIV's high degree of variability and adaptability means that the virus is able to change rapidly and usually develops resistance to treatments very quickly, rendering them ineffective.
However, the antibody, BI-201, acts on a protein outside of the infected cell, on a highly conserved epitope, meaning that resistance is much less likely to develop. In in-vitro tests that exposed the virus to the antibody for a long, continuous period of time, no resistance developed. The use of fully human antibodies also reduces the risk of side effects, a significant problem with current HIV treatments.
BioInvent's approval from the Medicines and Healthcare products Regulatory Agency in the UK has allowed it to initiate phase I/IIa trial that involves 36 untreated HIV-infected patients. The primary objective is to study safety, tolerability and pharmacokinetic properties of the candidate drug. A secondary objective is to study the effect on the viral load and thereby get the first indication as to how effective an antiviral drug BI-201 may be.
It is expected that the first patients will be recruited to the study soon and the results anticipated in the second quarter of 2006.
BI-201 is a human antibody selected from the Company's n-CoDeR antibody library for its ability to bind to the TAT protein. This protein is vital for HIV replication and, by neutralising TAT activity, BI-201 is expected to prevent the spread of the virus between human cells.
This action has been confirmed in in-vitro laboratory tests. Importantly, in drug resistance tests, BI-201 has been shown to inhibit the virus for 20 weeks without any development of resistance.
"We have passed an important milestone with the entry of our first candidate drug into clinical development," said Svein Mathisen, chief executive officer of BioInvent.
He added: "In less than three years we have taken our HIV project through discovery to clinical studies. The design of this first trial mean that we may have an indication of the drug's antiviral effect in one year's time."
HIV/AIDS drug resistance can be considered as a natural response to the selective pressure of the drug. However, it is exacerbated by several factors, including abuse, underuse or misuse of antimicrobials, poor patient compliance, and poor quality of available drugs.
At the last count in 2003, the World Health Organisation (WHO), estimated between 35-42 million people were living with HIV. In the same year, AIDS killed almost three million; over 20 million have died since the first cases of AIDS were identified in 1981.
The current crop of HIV/AIDS is a far cry from the initial round of antiretrovirals, which were launched between the years 1990 to 2000. Although products with lower pill burden, higher potency and fewer incidences of adverse side effects are gradually replacing these treatments, HIV infection rates are soaring.
The antiretroviral drug class slow down the replication and, therefore, the spread of the virus within the body, by interfering with its replication process in different ways.
Within this class is the Nucleoside Reverse Transcriptase Inhibitors (NRTIs), which reduce an enzyme called reverse transcriptase preventing the process that replicates the virus's genetic material. HIV needs reverse transcriptase to generate new copies of itself. GlaxoSmithKline's Abacavir (Ziagen), Bristol Myers Squibb's Didanosine (Videx, dideoxyinosine, ddI) and Roche's Zalcitabine (Hivid, dideoxycytidine, ddC) are examples of drugs in this class.
Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) also interfere with the replication of HIV by binding to the reverse transcriptase enzyme itself. This prevents the enzyme from working and stops the production of new virus particles in the infected cells. Pfizer's Delavirdine (Rescriptor), Boehringer Ingelheim Nevirapine (Viramune) are examples of drugs in this class.
Protease Inhibitors (PIs) inhibit the digestive enzyme protease that is needed in the replication of HIV to generate new virus particles. It breaks down proteins and enzymes in the infected cells, which can then go on to infect other cells. The protease inhibitors prevent this breakdown of proteins and therefore slow down the production of new virus particles.
GlaxoSmithKline's Amprenavir (Agenerase), Merck & Co's Indinavir (Crixivan) and Abbot Laboratories' Lopinavir and Ritonavir (Kaletra) are examples of drugs in this class.
Other drugs that inhibit other stages in the virus's cycle (such as entry of the virus and fusion with an uninfected cell) are currently being tested in clinical trials.
