Tibotec and J&J cleared to launch Aptivus rival

The FDA has granted accelerated approval for Tibotec and Johnson & Johnson's anti-HIV protease inhibitor Prezista (darunavir, previously known as TMC114) co-administered with ritonavir for use in combination therapy in treatment-experienced patients who have failed other antiretroviral therapies. 

Prezista belongs to a class of antiretrovirals known as protease inhibitors, or PIs. It is the second so-called non-peptidic PI to reach the market, the first being Boehringer Ingelheim's Aptivus (tipranavir), which was launched in June 2005 in the and in November 2005 in the and . 

Next generation

PIs work primarily by inhibiting the action of the viral protease enzyme, resulting in the formation of premature and defective viral particles unable to replicate further. Historically, this class has been associated with numerous problems, including high pill burden, toxicity and resistance. The first approved protease inhibitor was Roche's Saquinavir (invirase), which was poorly absorbed by the digestive tract and rapidly metabolized by the liver. In addition, the compound's short half-life resulted in patients having to take three capsules three times a day.

In the late 1990s, the development of ritonavir as a boosting agent helped resolve this issue for all PIs. Ritonavir, another protease inhibitor, blocks cytochrome P-450 CYP3A and 2D6 (two crucial drug metabolism pathways), thereby increasing serum levels of the antiretroviral drug. Co-administration with ritonavir therefore enabled the use of lower doses of other PIs, leading to a reduced pill burden for patients.

The launches of Prezista and Aptivus herald a new generation of protease inhibitors. While toxicity remains a key issue in this class, both drugs represent major breakthroughs in terms of drug resistance. They possess a novel molecular structure that enables binding to conserved residues on the protease enzyme, thereby minimizing the risk of development of resistance. 

The two drugs have displayed a high degree of potency in patients with multi-resistant HIV strains. These highly treatment-experienced patients often have few options left for therapy, so Prezista and Aptivus may offer new hope.

Since the launch of Saquinavir, eight other PIs have followed in succession, including Aptivus. In such a crowded market product differentiation is key, and even small differences between new and existing products may have a big impact on sales. 

Direct competition

Prezista and Aptivus could prove to be tough competitors. Making product differentiation difficult is the fact that both drugs have a novel resistance profile that will be of great value, and that both have been indicated for use in salvage therapy. In addition, the two drugs remain difficult to compare since they have been tested on different patient populations, with trial participants having quite different levels of treatment experience and resistance profiles.

However, pricing has been a major concern for some activists, with Aptivus and Roche and Trimeris' Fuzeon (enfuvirtide) - the only currently approved entry inhibitor - ranking among the top five most expensive HIV drugs on the market. In contrast, one activist group, The Fair Price Coalition Group, has welcomed the low pricing set by Tibotec and J&J for Prezista, giving the drug positive PR from an unexpected angle and thus possibly easing acceptance among HIV patients.   

Prezista's approval for use in treatment-experienced patients means it will compete directly with Aptivus. Since treatment regimens for HIV salvage therapy are quite diverse in comparison to earlier lines of therapy, no gold standard has yet arisen. This gives Boehringer Ingelheim and Tibotec the opportunity to define their respective drugs as the treatment of choice in this setting. It will be interesting, therefore, to observe which marketing strategies the competing companies choose, and which will gain the upper hand in the long-run.

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