Increased HIV survival rates generate upcoming treatment challenges

London- The demographics of HIV patients are shifting, with the average age of those infected with HIV ever-increasing due to longer life expectancy and higher survival rates. In fact survival rates have risen to as high as 91% in some markets. However according to a recent report by independent market analyst Datamonitor* (DTM.L), with increasingly complex infections and drug resistance developing in long term patients, novel medications and new combinations are being launched to continue the assault in a market that is providing challenges for pharmaceutical companies.

Historically, the HIV market has experienced relatively strong growth, recording a compound annual growth rate (CAGR) of 11.6% between 1999 and 2003. However a number of challenges, such as the first antiretroviral patent expiries, increased competition and a raft of novel products reaching the market, are expected to lead to a more modest CAGR of 6% to 2014. Despite this, Datamonitor believes the changing epidemiology of HIV, increased resistance development and a rise in incidence in several of the major markets offers companies involved in the therapeutic area significant sales opportunities.  See Commercial Insight: HIV - From the Naïve to the Complex.

Increased life expectancy, increased complexity

The demographics of the HIV infected population is rapidly changing, with Datamonitor's research finding that the average age of HIV patients is increasing, Datamonitor infectious disease analyst Laura Harris says. "Although there are a larger percentage of older patients acquiring the disease, which partially accounts for this changing demographic, Datamonitor believes that the key reason is the longer life expectancy for HIV/AIDS patients."

Before HAART, the time between infection and death was estimated to range from eight to 13 years, however now patients can expect a life expectancy equivalent to that of the general population, Harris says. "The advent of HAART has led to a substantial decrease in the mortality rate from AIDS, estimated to have fallen by 70% between 1995 and 2001(1) with survival rates now believed to be as high as 91%."(2)

However with longer life expectancy comes increasingly complex infections, with resistance development 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, Harris says. "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. Datamonitor estimates that the HIV pipeline, which includes the totally novel CCR5 inhibitors, as well as second generation NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside reverse transcriptase inhibitors) and PIs (protease inhibitors), could generate 41% of expected 2014 HIV sales, Harris says.

Meeting changing patient needs

As patients become more treatment-experienced, key factors such as dosing frequency and side effects become increasingly vital to compliance and therefore, prescription decisions. "The rapid uptake of Bristol-Myers Squibb's (BMS) PI Reyataz (atazanavir), which offers once-daily dosing and a reduction of the adverse lipid effects common to the PI class, highlights the growing preference for products which provide minimal impact on a patients lifestyle. 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, has led to reformulation of leading products becoming a preferred lifecycle management strategy to maintain sales."

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

For those HIV players with several antiretroviral products, such as GSK and Gilead, fixed dose combinations (FDC) are becoming a favored option. The recent approvals of GSK's Epzicom (lamivudine/abacavir) and Gilead's Truvada (tenofovir/emtricitabine) increased the number of marketed FDC's to five, four of which are in the HAART-backbone NRTI class, Harris says. "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 Gilead agreed to collaborate in the development of a once-daily, fixed-dose combination (FDC) of Gilead's two NRTIs, Viread (tenofovir) and Emtriva (emtricitabine) and the NNRTI Sustiva (efavirenz).  Although intended for the Third world, such a combination would certainly be welcomed for use in the developed markets, Harris says.

Challenges in the US, opportunities in Japan

The US has traditionally dominated the HIV market in terms of sales, generating $3.8 billion, or 68% of 2003 sales(3). However, opposition to rising pharmaceutical prices is growing in the US, exacerbated by the premium price of Fuzeon and the 400% Norvir price increase in December 2003, Harris says. "Despite increasing downwards pressure on drug prices, Datamonitor believes the US will remain the largest market in terms of antiretroviral sales, accounting for 62% ($6.7 billion), as HIV prevalence is expected to reach 1.3m by 2010(4)."

In contrast, the smallest market will experience the most rapid growth to 2014. The Japanese market, which currently accounts for only $56m (1%) of HIV sales, is forecast to more than treble by 2014, reaching sales of $200m. Currently, only 0.01% of Japan's total population is believed to be living with HIV/AIDS(5) but The WHO has stated that Japan is one of the most likely candidates for a new wave of HIV infections, and estimated that prevalence could be as high as 50,000 by 2010, Harris says. "An increase in risk behavior is the key driver of this rise in Japanese HIV incidence, with indicators including condom sales falling by 25% since 1993 and a rise in unwanted teenage pregnancies."

While transmission through blood products has been largely eradicated in the US and EU through widespread screening, it still occurs in Japan, albeit rarely. "It is estimated that approximately 80% of people are unaware that they are infected, raising the prospects of unknowing transmission."

Datamonitor believes that the Japanese market offers significant opportunities for companies with an HIV portfolio. Alliances with local companies, taking advantage of their domestic knowledge and presence, will enhance the prospects for benefiting from this growth. Indeed, Roche and Gilead have already established themselves in this way, through agreements with Chugai and Japan Tobacco, and appear well-positioned for the possible Japanese HIV boom, Harris says.

"As HIV therapy reaches a more mature phase, with HAART established as the key treatment paradigm and patients' life expectancy now comparable to that of healthy individuals, the antiretroviral market is also entering a new cycle. Companies involved in the antiretroviral market will have to employ new portfolio management strategies to ensure they are optimally positioned to defend against sales erosion."

"As more products with similar attributes, and even more with unique characteristics, become available, product positioning, physician targeting and promotional activity is likely to become increasingly important to the successful launch and subsequent sales maintenance of new drugs."

Ends

Related Report: Datamonitor - Commercial Insight: HIV - From the Naïve to the Complex - click here!

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