HIV market: collaborative combinations
pharmafile | March 26, 2007 | Feature | Research and Development, Sales and Marketing |Â Â HIV, drug development, marketingÂ
Two new HIV drugs, from Tibotec and Gilead, have been shown to be viable late-stage pipeline candidates. However, both TMC278 and elvitegravir are set to compete head-to-head against more widely-used competitors. In the longer term, both candidates could improve usage and penetration through use in collaborative combination therapies.
TMC278, developed by Johnson & Johnson's Belgium-based Tibotec unit, could prove to be a formidable competitor to Bristol-Myers Squibb's market-leading, non-nucleotide reverse transcriptase inhibitor (NNRTI) Sustiva (efavirenz), especially in light of newly released resistance data from the CDC highlighting NNRTI resistance as the most common form of resistance, occurring in 6.9% of patients. Tibotec's second NNRTI has already been shown to have good activity against common NNRTI resistant strains of HIV.
Meanwhile, preliminary data from Gilead's elvitegravir phase IIa trial successfully demonstrated a statistically superior reduction in viral load at 24 weeks, compared to the protease inhibitor comparator. The integrase inhibitor is the second in this eagerly awaited class to undergo clinical trials, and it may form an ideal combination candidate for use with regimens requiring ritonavir boosting (such as Boehringer Ingelheim's Aptivus).
Stiff competition
However, both candidates face stiff competition from products that are either currently on the market, or further down the road to approval. TMC278 will compete directly with the incumbent drug of choice as a backbone for treatment combinations, Sustiva (efavirenz) from BMS. Meanwhile, if approved, elvitegravir will lag behind Meck's MK0518 by at least one year to the market.
Accordingly, the clinical trial design for the phase III studies must be very carefully considered for both compounds in order to ensure optimal positioning and uptake. In the case of TMC278, an apparent lack of an efficacy benefit over Sustiva will need to be overcome by other differentiating factors.
Two routes seem likely: the safety and tolerability profile, and a proven track record of activity against increasingly common NNRTI resistance. If TMC278 does not require up-front resistance testing before therapy initiation, it could gradually replace the NNRTIs of Sustiva's generation. The US trial data suggest that among newly diagnosed patients, some 6.9% show some form of NNRTI resistance.
However, it will require considerable commercial muscle in order to dislodge Sustiva. BMS' inclusion of Sustiva in Atripla has further embedded its penetration and ensured a commercial presence in protected form in the run up to an anticipated 2012 patent expiry.
Combination therapies
Tibotec's plans for TMC278 must therefore include a means of encouraging a rapid uptake. This could potentially be achieved by integration into a once daily combination for treatment nave or first-line patients. GSK's Combivir (lamivudine and zidovudine) or Gilead's Truvada (emtricitabine and tenofovir disoproxil fumarate) are potential candidates for such a combination. However, given Gilead's involvement with BMS and Merck in Atripla, Tibotec's options may be limited to partnering with GSK.
Elvitegravir, meanwhile, faces the prospects of a launch well after that of key competitor MK0518. While trial data for both candidates is still required, Merck has proposed that MK0518 could be on the market by early 2008, while Gilead believes elvitegravir is not likely to be available before 2009. Once again, a combinational approach may be a means of overcoming this disadvantage.
Elvitegravir requires ritonavir boosting, and as such, may be ideally suited to a combination involving other products that similarly require ritonavir co-administration. The new, so-called non-peptidic Protease Inhibitors (PIs) such as Aptivus (tipranavir, Boehringer Ingelheim) and Prezista (Darunavir, Tibotec) are obvious potential candidates. Because of their novel resistance profiles which are significantly different from most other PIs, their use is reserved for heavily treatment-experienced patients and salvage situations, limiting their patient potential.
Although patients in first-line therapy will remain the largest segment of the market, improved survival rates lead to a gradual increase of the numbers of patients in later lines of therapy. In conjunction with a growing level of resistance amongst newly diagnosed patients, such a combination therapy could become increasingly valuable to all stakeholders.
Collaborations to change competitive landscape
The BMS, Gilead and Merck collaboration on Atripla opened up a new frontier in positioning HIV therapies. In order to maximise potential for product penetration, individual players increasingly have to reconsider competitive landscapes.
As treatment options and complexities have increased in HIV, an additional tier of competitive analysis is required beyond a simple product or portfolio face-off between two companies. Both Tibotec and Gilead have potentially promising candidates. However, even prior to launch, their consideration of potential collaborative partners may be the most effective means of competing effectively with more established competitors.
Related links:
Commercial Insight: HIV – Change of guard
Pipeline Insight: HIV – Extending treatment options
Stakeholder Insight: HIV – A way of life
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