Therapeutic focus – Novel HIV approaches continue to suffer lack of interest

This week’s International AIDS Conference in Vienna throws the annual spotlight on the pipeline of candidates that might offer a particularly novel or radical approach to treating a disease which, in the Western world at least, is becoming an increasingly chronic and manageable one.

While the overall pipeline remains dominated by small molecule-based therapies, admittedly aimed at more novel targets, what some researchers continue to strive for is a major breakthrough from other technologies which have revolutionised other therapeutic areas, such as vaccines and antibodies. While such hopes are understandably raised each year at these conferences, the tables below reveal a distinct lack of interest and investment, particularly from big pharma players, in more novel approaches to tackling the HIV virus. In some respects, for example, the prospect of developing an HIV vaccine, one of the industry’s biggest targets since the virus exploded on to the scene in the early 1980s, remain as remote as ever.

In control

Symptoms of the disease were first identified in 1981, and by 1984 the HIV virus was classified as the root cause of AIDS. Astonishingly, just three years later in 1987 the first major drug was approved, azidothymidine (AZT), a so-called nucleoside analogue reverse transcriptase inhibitor (NRTI) which remains one of the main classes of agent used in HIV therapy today.

The HIV market has grown rapidly, particularly in the Western world, and last year reached $14.3bn globally. Indeed, despite reports that market need has largely been met and saturated, sales of HIV drugs will continue to grow 5% annually to $19.9bn by 2016, analysts believe.

Worldwide HIV Drugs Sales WW annual sales ($m) Market Share
2009 2016 CAGR (09-16) 2009 2016
 1  Gilead Sciences  5,567  9,590  8%  39%  48%
 2  Johnson & Johnson  818  2,595  18%  6%  13%
 3  Merck & Co  958  2,259  13%  7%  11%
 4  Bristol-Myers Squibb  1,860  1,954  1%  13%  10%
 5   ViiV Healthcare (GSK + Pfizer)  2,683  1,579   (8%)  19%  8%
 6  Abbott Laboratories  1,719  1,444   (2%)  12%  7%
 7  Boehringer Ingelheim  433  221   (9%)  3%  1%
 8  Torii Pharmaceutical  58  122  11%  0%  1%
 9  Shionogi  -  96  n/a  -  0%
Other 157 89
Total HIV Drug Market 14,253 19,949 5%

The current market remains dominated by NRTIs, NNRTIs, protease inhibitors and integrase inhibitors. Likewise, the most promising pipeline candidates are also expected to be fresher graduates from the same classes of drugs.

The table below highlights the numbers of products adopting a more novel approach to tackling HIV, either as a prophylactic or treatment. Of the 250-odd pipeline candidates overall, just 76 are from one of four newer classes: vaccines, antibodies, gene therapies and antisense therapies.

Count of novel pipeline HIV candidates
Status Vaccines MAbs Gene therapy Antisense Overall
  Phase III  2  -  -  -  2
  Phase II  10  3  2  -  15
  Phase I  20  2  1  1  24
  Pre-clinical  25  6  2  2  35
Report Total  57  11  5  3  76
Abandoned projects 38 13 3 2

While 57 vaccine candidates may be in active development, almost 40 projects have fallen by the wayside, a failure record perhaps indicative of the current lack of interest in the area.

Understandably the novel scene is dominated by vaccine approaches and the table below highlights some of the late-stage candidates.

However, the most advanced vaccine, Sanofi-Aventis’ Alvac-HIV, is a case in point in terms of the overall neglect this field has received in recent years. Despite reporting encouraging phase III results late last year in a 16,000 patient trial in Thailand, in combination with VaxGen’s Aidsvax, Sanofi, one of the biggest vaccine makers worldwide, has largely washed its hands of it, inviting further investment from public-private partnerships.

Furthermore, the vaccine candidate itself has been in development for some time now, originally developed by Rhône-Poulenc, one of the historical forerunners of Aventis and now Sanofi-Aventis. More than 25 years on from identifying HIV, Sanofi claims the clinical data from Thailand to be “the first concrete evidence…that a vaccine against HIV is potentially feasible”, quite an indictment on the lack of real progress with the technology; although admittedly the constantly revolving and mutating targets presented by HIV represent one of the biggest challenges in modern medicine. 

Meanwhile VaxGen’s candidate failed in two phase III studies in 2004 and the company has since given up all further direct involvement, licensing it on to Global Solution for Infectious Disease, a not-for-profit group.

It seems until one of these novel approaches produces the kind of clinical data that really makes big pharma pay attention, for now it will be left to the small biotechs and public-private enterprises of the world to plough a somewhat lonely furrow.

Selected late stage novel HIV pipeline candidates
Status Product Company(s) Pharmacological Class
Phase III
Vaccine ALVAC-HIV Sanofi-Aventis HIV vaccine
AIDSVAX VaxGen/Global Solution for Infectious Disease HIV vaccine
Phase II
 Vaccine AGS-004 Argos Therapeutics/Kyowa Hakko Kirin RNA-loaded dendritic cell immunotherapy
DNA/MVA Vaccine GeoVax Labs HIV vaccine
Global HIV Vaccine GenVec HIV vaccine
HIV DNA Vaccine Vical HIV vaccine
HIV Vaccine (MVA-BN-Multiantigen) Bavarian Nordic HIV vaccine
tgAAC09 Targeted Genetics HIV vaccine
TUTI-16 Thymon HIV vaccine
V526 Sanofi-Aventis HIV vaccine
Vacc-4x Nutri Pharma HIV vaccine
Vacc-5q Nutri Pharma HIV vaccine
Monoclonal antibody HIV Antibodies therapy Polymun Scientific Anti-HIV agent
PRO 140 Progenics Pharmaceuticals/Abbott Laboratories Anti-CCR5 MAb
TMB-355 (ibalizumab) TaiMed Biologics/Roche Anti-CD4 MAb
Gene therapy VRX496 (lexgenleucel-T) VIRxSYS/Takara Bio/Oxford BioMedica Anti-HIV gene therapy
HGTV43 Enzo Biochem Anti-HIV gene therapy

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