AIDS activists ask AVEXA to reconsider decision to abandon apricitabine

[Guest guest]

June 17, 2010

Dr.

Former Senior Vice President, Drug Development at Avexa

Cc: Drona, Chairman of the Board at Avexa

Kerr, Board

Secretary

We, the undersigned, are asking the

decision makers at Avexa to reconsider the decision to stop the development of

apricitabine, a nucleoside analog that has shown good efficacy in patients with

the most common nucleoside mutation, M184V. Physicians and a growing

number of patients with limited treatment options have been counting on the

approval of this drug to enable the construction of effective regimens.

Apricitabine can mean the tipping point between success and failure of a

salvage regimen – between life and death.

It is well known that the management

of multidrug resistant HIV has improved dramatically with the recent approval

of a number of highly effective antiretroviral drugs, including raltegravir,

maraviroc, darunavir, and etravirine. Despite the impressive effectiveness of

these drugs in clinical trials, a growing subset of patients continues to

exhibit virologic failure in clinical practice – even when adherence is good.

Most of these treatment failures likely occur because of an inability to

construct a regimen containing two to three fully effective agents for

individuals with extensive prior exposure to antiretroviral drugs. Some of

these patients acquired drug resistance while participating in clinical trials.

Failure rates in recent phase III studies such as DUET (etravirine and darunavir),

MOTIVATE (maraviroc), and BENCHMRK (raltegravir) were in the 27-40% range. Many

of the patients who experienced virologic failure while participating in these

studies were subsequently unable to construct suppressive regimens.

The prevalence of multidrug

failure in clinical practice is not well documented, however there are signs

that the number of patients in need of new options is growing. Deeks and

colleagues at UCSF/SFGH have an ongoing observational cohort of patients who

have developed drug resistant HIV (the SCOPE cohort). Most of these patients

have been able to construct a fully suppressive regimen and are currently doing

well. However, of the original 300 patients, approximately 40 now have evidence

of having failed all six therapeutic drug classes. These 40 patients have a GSS

of either zero or one, and have no clear options for suppressing HIV

replication. Many have advanced disease (CD4 < 100) and hence may not be

able to wait for the development and approval of multiple new options.

A 2009 survey of 94 responding

HIV clinicians in the United

States found approximately 250 patients

unable to construct a viable regimen due to resistance. In contrast to a

common assessment heard in 2009, several key clinicians now recognize that the

latest generation of drugs has not proven as durable as they had hoped, and

that resistance is slowly reemerging as a problem for some patients. Although the

number of multidrug resistant patients with no treatment options may be

relatively small, there is concern that this may be the tip of the iceberg and that the

industry will not be prepared to meet the need for newer drugs with unique

resistance profiles.

The options for constructing a three-active

agent regimen for this growing population during the next four years appears to

be few, which means that the chances for survival for those with lower CD4

cells counts are diminishing. Consequently, an early expanded access program

that makes available current investigational agents that have progressed beyond

phase II could help improve the outlook for survival for these patients in

need. But the drugs must remain in development.

Other small companies developing

new HIV drugs, such as TaiMed and Myriad have faced the same difficulties in

finding partners that Avexa has. Of these companies’ drugs, though, apricitabine

stands out as a member of a well-understood class, the one nearest to approval,

and as an agent addressing one of the most common forms of drug resistance

among all people with HIV (including those still naïve to treatment). For the

salvage population, convenience in dosing is not the issue: activity is! In our

recent meeting with the major HIV drug makers we have been raising awareness

about the growing unmet need for new salvage options, and as they hear this

message from community and clinicians, they have begun to pay attention. Researchers

and statisticians are also working on creative ways to conduct registrational

clinical trials in an environment when there are many effective options and a

relatively small subject pool (the Forum for Collaborative HIV Research is

holding a workshop on this issue in October 2010). Finally, the FDA has said it

recognizes the need for new salvage therapies and appears willing to work with

companies to bring new products to market in this difficult environment. The

tide is turning; this is not the time to abandon apricitabine.

We the undersigned believe that

apricitabine is a potentially important drug, and one of the few products

currently in the pipeline that could help patients with multidrug resistance

tip the balance in favor of viral suppression, health, and, for many, life

itself. We ask that Avexa reconsider its decision not only based on

potential sales but also on the survival of patients at risk.

Sincerely,

The Members of the AIDS

Treatment Activists Coalition- New

York, New York

The Members of the European AIDS

Treatment Group- Brussels, Belgium