HIV pipeline offers optimistic outlook over the longer term
SummaryOf the 27 drugs currently in the HIV clinical development pipeline, the majority are in either Phase II trials or earlier. While the pipeline is considered strong, it is unlikely that any major treatment advances will be made before 2009/10. In fact, two of the more advanced drugs in terms of development - tipranavir and capravine - are likely to be used merely as 'holding drugs'.
The HIV market has historically experienced relatively strong growth, recording a compound annual growth rate of 11.6% between 1999 and 2003, and the current HIV pipeline is predicted to generate an additional $4.6 billion in sales by 2015. However, price constraints, patent expiries, generic incursion and a limited increase in patient numbers means, overall, the HIV market will experience much more modest growth, with a CAGR of 5.5% between 2004 and 2015.
Nevertheless, by 2015 pipeline products will account for 38% of total antiretroviral sales, justifying optimism for future therapeutic advances, though it is unlikely that this value will be realized before 2009/2010, as the most promising pipeline compounds are in Phase II trials or earlier.
In the pipeline
The most advanced developmental antiretrovirals are Boehringer Ingelheim's tipranavir and Pfizer's capravirine, which are due to be launched in 2005 and 2007 respectively. Both drugs were initially viewed optimistically, with early pre-clinical studies for capravirine revealing sensitivity to 90% of subjects with high-level resistance to most existing non-nucleoside reverse transcriptase inhibitors (NNRTIs), a good viral load drop, and the possibility of once-daily dosing. Similarly, tipranavir's activity against protease inhibitor (PI) resistant virus led to the possibility of additional lines of therapy for treatment-experienced, highly resistant patients.
However, more recent data has tempered enthusiasm somewhat, with adverse pharmacokinetic data, inconsistent activity and a lack of clarity as to their positioning in the market resulting in confusion as to the true usefulness of the drugs in therapy. For example, while tipranavir has been trialed with Fuzeon, indicating that it could be used in late stage or salvage therapy, there are also studies in naive patients, reflecting a potential position in earlier therapy.
One UK-based opinion leader interviewed by Datamonitor echoed this uncertainty: "I think the other weakness is its [tipranavir's] lack of positioning, a kind of weakness of Boehringer to actually take a gulp and say, this is where we want to put our drug. And I think if they put it in the wrong place, it could be in trouble. They're just being squeezed. They're in the wrong place at the wrong time."
More effective treatments expected
These issues, combined with the fact that more potent drugs are currently being developed and may be launched by 2009/2010, has led to both tipranavir and capravirine being viewed as 'holding drugs'. In essence; they satisfy an immediate unmet need, but will be superseded as new more efficacious products are subsequently launched. For example, it is widely believed that the launch of Tibotec's PI TMC-114 will lead to switching away from tipranavir, positioning TMC-114 as the drug of choice for PI-experienced, resistant patients.
Similarly, several NNRTIs such as Tibotec's TMC-125 and TMC-278 are being developed, both demonstrating superior potency and strong resistant profiles. Indeed, one opinion leader even commented that he thought capravirine had been withdrawn from development, highlighting the likelihood that should capravirine successfully reach the market, it will probably have a short shelf life.
Ultimately, the most advanced developmental compounds are expected to provide a slight advance in HIV treatment, but will be rapidly replaced following the subsequent launch of earlier stage pipeline products. However, it is the drugs within the entry inhibitor (EI) class which are expected to provide the real step up in therapy, with a total paradigm shift being touted as a real possibility.
While NRTIs can be expected to remain the dominant class, potentially contributing 38% of total sales by 2015, this is dependent on the impact of the EIs. The effect of this class on the market is still unclear due to the early stage of development that most of the drugs are in. Furthermore, with Fuzeon representing the only EI in-market, little precedent has been set. Pipeline EIs include Schering-Plough's SCH-417690, Pfizer's UK-427,857 and GlaxoSmithKline's GW873140, which comprise the CCR5 inhibitor class, as well as Panacos's PA-457 and Progenic's PRO-140 and PRO-542.
There are two potential scenarios for the future of the EI class. In the first case, the CCR5 inhibitors will be used in first-line therapy, thus creating a treatment-paradigm shift, as established combinations are pushed back to be used in treatment-experienced patients. Indeed monotherapy with the CCR5 inhibitors was also mentioned by several KOL's as a real possibility for the future. Should the CCR5 inhibitor's be used in naive patients, in first-line therapy, sales in excess of $2 billion by 2015 could be generated, with share taken from the three established classes.
However realistically, this scenario is considered as a 'wild-card' due to the fact that physicians are unlikely to rapidly adopt new drugs in such a way so early on. Consequently, the second and more plausible scenario is where the developmental EI drugs will be used in late-stage and salvage therapy, possibly in combination with Fuzeon, resulting in class sales of just under $1 billion by 2015.