Pumping Life Into the HIV PipelineIncreasingly, companies - faced with pressure on pricing and patents, as well as the inherent difficulty in tackling innovative targets - are strategically shrinking the number of HIV products in the development pipelines.
October 22, 2004
The human genome project, which promised to be a boon for drug development, is yet to lead to one successful product. New technology meant newer and better therapies and researchers forecast an era of designer drugs, tailored to an individual's genetic makeup or rationally designed to target a specific protein. But a drug revolution has not followed the genomic revelation, causing leaders in the field to label it the "disappointing genome". Pharmaceutical companies still struggle to push products to market and, more than ever, they fail.
Finding drug candidates is not the problem. The total number of drugs in the development pipeline has steadily increased since the mid-90s as companies continue spending more money. Fewer new medicines, however, are being approved. Instead, drug companies are dropping compounds in the later, more expensive stages of development.
Eliminating drugs in phase II or III development, the final steps before reaching consumers, is costly and inefficient. Industry advisors urge companies to make the critical decision on development as early as possible and drug companies are now looking at ways to speedily assess a candidate. Such methods include experimenting with better animal models, testing in humans earlier, and formulating and manufacturing drugs as early as phase I.
These measures can only marginally improve efforts to get new products to market. Nearly half of all drugs discontinued between 2000 and 2004 were not discarded due to safety or efficacy issues. Rather, potentially beneficial compounds were sidelined based on what pharmaceutical companies call strategic or marketing decisions, according to Pharmaprojects, a global pharmaceutical tracking company in London.
This is particularly the case in HIV. The mergers and acquisitions that dominated the industry recently also contribute to the waning of compounds that come to market. Due to the overlap of programs when two large companies meld into one, many potential medicines are discarded later in development. When Bristol-Myers Squibb acquired Dupont Pharmaceuticals in 2001 both programs were heavily invested in HIV. The commonality of their programs, however, led to four anti-HIV compounds being permanently shelved.
Throughout the world, drug companies have found the costs of HIV research mounting but the global market for their products limited since the countries where the need is greatest are often quite poor. Also, countries with large HIV populations are allowed to make or import generic versions of patented AIDS drugs. Even countries with more developed economies, such as Brazil and Thailand, are manufacturing their own HIV medicines. Drug companies are therefore recouping their development costs by charging high prices for their products in the US. But this does not seem to be enough to fuel investment in a wide variety of therapeutic targets.
Faced with fewer new drug launches and market pressure, many companies are now taking another approach: consolidating their pipelines to concentrate on only five or six disease targets. This trend, illuminated at the Drug Discovery Technology meeting in August, allows companies to pump more money into established or promising programs or where pricing pressure is less significant. Accordingly industry analysts witnessed a huge increase in anticancer research over the past 10 years. The number of anticancer drugs in development is growing faster than for any other disease.
But streamlining disease targets could be bad news for finding new drugs to fight HIV. Unlike the number of drugs across other therapeutic areas, especially cancer, the quantity of anti-HIV drugs in research and development steadily decreased during the years 1997 to 2001, according to Pharmaprojects data. Despite approval of several new antiretrovirals last year, the number of compounds in active development has rallied only slightly in the past 2 years.
And many companies working on HIV continue investing in drugs that target viral enzymes on which many approved drugs already act. According to reports at the International AIDS Conference this summer in Bangkok, research into new HIV targets stands at a preliminary stage. Tackling novel targets means both opportunity and risk.
The focus of Merck's HIV program is the viral enzyme integrase. Drugs that inhibit HIV's other enzymes are plentiful, but integrase inhibitors are particularly elusive. After more than 14 years of research at Merck, not a single compound has entered phase II development. Such setbacks throughout the company, including dropping two drugs in phase III last year and witnessing many products come off patent, forced Merck to alter its long-time business strategy. The company always relied on internal discovery of drug candidates. Merck now leads the industry in "in-licensing" compounds from outside companies to bolster its pipeline. Last year alone Merck bought 47 compounds, compared to only 10 in 1999.
Other companies involved in HIV drug research have faltering pipelines. Pharmaprojects data indicate that of nine large pharmaceutical companies currently involved in HIV (Abbott, Bristol-Myers Squibb, Boehringer Ingelheim, GlaxoSmithKline, Gilead, Merck, Pfizer, and Roche) only Boehringer and Glaxo have more compounds in development this year than last. Development at Abbott, Gilead, and Pfizer declined precipitously in recent years. Meanwhile more innovative drugs, like the CCR5 and integrase inhibitors, remain years away.
Without robust programs looking for novel approaches to treat HIV, big pharmaceutical companies will increasingly depend on the innovation of smaller biotechs, who collaborate to bring new drugs to people in need. Otherwise companies may abandon their HIV research efforts entirely. Although Abbott purports to focus its antiviral program on inhibitors of HIV and hepatitis C, the Pharmaprojects database lists no activity in HIV.
Abbott faced public excoriation early this year after drastically raising the price of the drug ritonavir (Norvir). Because ritonavir is rarely taken alone, rather in combination with drugs made by competitor companies, many saw this as a way for Abbott to make its other anti-HIV drug (Kaletra) more attractive. Members of the HIV community and several physicians were outraged and engaged in a public relations battle with the company. Now, Abbott may be an example of a company that has completely pulled out of the HIV market.
Analysts from Pharmaprojects also caution that new companies are unlikely to delve into HIV research with the mounting pressure on drug pricing in the US and the threat of re-importing prescription drugs from Canada. This further confounds the future of HIV drug development.
Despite pricing controversies and difficulty in finding new therapies, better drugs to treat HIV are important and necessary. The growing population of people in the US who have exhausted all available combinations of antiretrovirals will ultimately pay the price if the pharmaceutical companies do not work to fill their HIV pipelines.
Kristen Kresge is a Research Associate at the American Foundation for AIDs Research (amFAR).