Avexa halts apricitabine development due to cash shortage

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Avexa announced on Monday that it is halting the development of its nucleoside analogue reverse transcriptase inhibitor apricitabine because it cannot find a partner to develop the drug and obtain licensing in key markets. The company cannot afford to develop the drug alone.

The Australian company’s shares fell by 79% on the Sydney stock exchange after the announcement, which come despite positive clinical trials results for the product.

Avexa said that negotiations with other companies had proved difficult due to the high dosing requirement of the drug (800mg twice daily), which would make it difficult to coformulate with other antiretrovirals.

Glossary

treatment-experienced

A person who has previously taken treatment for a condition. Treatment-experienced people may have taken several different regimens before and may have a strain of HIV that is resistant to multiple drug classes.

reverse transcriptase

A retroviral enzyme which converts genetic material from RNA into DNA, an essential step in the lifecycle of HIV. Several classes of anti-HIV drugs interfere with this stage of HIV’s life cycle: nucleoside reverse transcriptase inhibitors and nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). 

nucleoside

A precursor to a building block of DNA or RNA. Nucleosides must be chemically changed into nucleotides before they can be used to make DNA or RNA. 

integrase inhibitors (INI, INSTI)

A class of antiretroviral drugs. Integrase strand transfer inhibitors (INSTIs) block integrase, which is an HIV enzyme that the virus uses to insert its genetic material into a cell that it has infected. Blocking integrase prevents HIV from replicating.

phase III

The third and most definitive stage in the clinical evaluation of a new drug or intervention, typically a randomised control trial with the new intervention compared to an existing therapy or a placebo, in large numbers of participants (typically hundreds or thousands). Trial results are used to evaluate the overall risks and benefits of the drug and provide the information needed for regulatory approval.

Potential partners were also concerned by the difficulty in determining the potency of the drug. The use of new high active agents in the optimised background regimen, which make it easier for treatment-experienced patients to achieve an undetectable viral load, may mask the effectiveness of apricitabine, some argued.

Apricitabine (ATC) was being developed for use in patients with NRTI resistance. A phase III study was halted after 24 weeks in October 2009. This study compared apricitabine to 3TC in patients with 3TC resistance receiving an optimised background regimen.

A press release in March 2010 revealed that when compared to the 3TC group, patients in the apricitabine group experienced an additional viral load reduction of 0.4log, and did not state what proportion of study participants in each arm achieved a viral load below 50 copies/ml.

"The rationale for closing the trial, which was expected to run through 2011, was based on two key factors, “ said Avexa chief executive Julian Chick. “First, the results may offer key insight into ATC's role in the overall HIV treatment landscape and discussions with regulatory authorities may clarify the ATC approval path. Secondly, this will allow for a mature enough data point to enable potential partners the ability to make a definitive decision on the licensing of ATC."

Apricitabine had been in development for over ten years. Avexa bought the drug from Shire in 2005, and the company planned a major programme of HIV drug development. It licensed a CCR5 inhibitor, nifeviroc to the Chinese company Target Pharmaceutical.

Earlier this year Tibotec turned down the option to develop a number of candidate integrase inhibitors discovered by Avexa.

Avexa said that it would still seek licensing agreements for apricitabine in regions outside North America, but did not expect any deals to recoup the cost of development.