HIV infection - changes in epidemiology driving R&D development and increased market value

Globally, the number of people living with HIV continues to grow from 35 million in 2001 to 38 million in 2003. An estimated 5 million people acquired HIV in 2003, the greatest number in any one year since the beginning of the epidemic, and in the same year almost three million died as a result of AIDS taking the total to 20 million since the first cases of AIDS were identified in 1981.

The demographics of the HIV infected population is rapidly changing. Although 2003 saw a jump in the number of newly identified global HIV infections, the incidence of new infections in the developed world has stabilized (most recent  statistics from the CDC report 25,174 and 26,463 new infections in 1999 and 2002 respectively). Treatments of HIV have also improved with the advent of HAART. Before HAART, the time between infection and death was estimated to range from eight to 13 years, however now, in the developed world, patients can expect a life expectancy equivalent to that of the general population. HAART has led to a substantial decrease in the mortality rate from AIDS, estimated to have fallen by 70% between 1995 and 2001 with survival rates now believed to be as high as 91%. Mirroring the reduction in mortality, the average age of HIV patients has increased. For example in 1999, nearly 59,000 Americans over the age of 45 were infected with HIV; this figure now stands at over 94,000.

Paralleling changes in HIV epidemiology is a most definite ascension in the development of new HIV therapeutics. In fact Datamonitor estimates that the HIV pipeline could generate 41% of expected 2014 HIV sales. Datamonitor's recent market analysis and survey of 32 HIV pipeline products (Phase I to Phase III) suggests that by 2012, global product sales could amount to just under $12 billion, approximately double the value recorded for 2003 ($5.76 billion).

HIV R&D activity is being driven in part by the increasing complexity of infection that accompanies longer life expectancy. Resistance development is now common in patients undergoing long-term antiretroviral therapy. Traditionally, patients who developed resistance after second-line therapy were limited in their choices for subsequent therapy. Currently, the development of newer drugs such as Fuzeon, with activity against resistant strains of HIV, has increased the options for later stage patients.

Many of the antiretrovirals currently in development, such as tipranavir and capravirine, have potent activity against HIV-resistance and are likely to facilitate third, fourth and even greater lines of therapy for the most treatment-experienced patients.

Despite the efficacy of existing HAART therapeutics their side-effects threaten compliance introducing yet another R&D driver. Likewise the massive pill burden associated with HAART, which can range from three pills taken once daily to over 18 tablets taken three times a day also represents a key problem. Consequently, reformulation of leading products to reduce pill burden has become a preferred lifecycle management strategy to maintain sales. The need to reduce pill burden has also driven the development of new agents and in 2003, Reyataz (atazanavir) became the first once-daily protease inhibitor (PI) to receive FDA approval for the treatment of HIV in combination therapy. Reyataz, which also demonstrates a reduction of the adverse lipid effects common to the PI class, has since experienced rapid uptake.

Both Abbott and , whose PI products Kaletra and Invirase, respectively, have been negatively impacted by the launch of Reyataz, have begun the process of reformulation, submitting new formulations of their drugs for approval in summer 2004. With the launch of GSK's fosamprenavir (Lexiva in the , Telzir in ), which can be taken once-daily in selected patients, these reformulations will play a vital part in maintaining Kaletra and Invirase sales to 2014.

For those HIV players with several antiretroviral products, such as GSK and , fixed dose combinations (FDC) are becoming a favored option. The recent approvals of GSK's Epzicom (lamivudine/abacavir) and 's Truvada (tenofovir/emtricitabine) increased the number of marketed FDC's to five, four of which are in the HAART-backbone NRTI class. FDC's offer dosing convenience, allowing patients to take one pill rather than the individual components and, in some cases could reduce adverse effects and drug interactions. However, while single-class FDC's offer a range of benefits, attention has moved to cross-class combinations, many of which are already widely used in the developing world.

In May 2004, BMS, Merck & Co. and agreed to collaborate in the development of a once-daily, fixed-dose combination (FDC) of 's two NRTIs, Viread (tenofovir) and Emtriva (emtricitabine) and the NNRTI Sustiva (efavirenz). Although intended for the developing world, such a combination would certainly be welcomed for use in the more mature markets.

In addition to new HAART therapies novel approaches that prevent cellular entry of HIV also feature highly in the drug development sector. In fact within the HIV pipeline, around a third of candidates are classified as entry inhibitors/others. Datamonitor predicts that in 2012, 16% of total sales revenue could be derived from these novel compounds. Candidates such as the CCR5 antagonists SCH-D, GW873140, UK-427, 857 and the CD4 inhibitors such as BMS-488043 presently appear safe and orally available, but more importantly, are being developed by major players

Thus, far from being a stagnant area of the drug discovery sector, HIV therapeutics represents a dynamic field and it is estimated that the number of companies involved in this field will grow by 150% over next 10 years.

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(Source LeadDiscovery, October, 2004)