Global Insight Perspective | |
Significance | The European Commission has dropped the "exceptional circumstances" clause surrounding the approval of Aptivus, granting it full marketing approval. |
Implications | This means that the Boehringer Ingelheim drug can now be prescribed for all highly treatment-experienced adult HIV patients in the EU. Greater prescribing of the drug might be slow to occur in some markets, however, due to Aptivus's high price and varying reimbursement status across countries. |
Outlook | Boehringer Ingelheim is pursuing more clinical trials in order to assess Aptivus's efficacy in different patient populations, namely specific ethnic groups and children. Results thus far seem encouraging, and the company could seek to extend Aptivus's approved indication within the next year or two. |
The European Commission has granted full marketing authorisation for Aptivus (tipranavir) to be used in conjunction with ritonavir for surpressing HIV in patients who are "highly treatment experienced" and consequently have developed immune resistance to other protease inhibitors. Produced by German pharma heavyweight Boehringer Ingelheim, Aptivus has been available within the European Union (EU) since 2005, when it was first approved by the Commission. At the time, however, approval for the drug was somewhat limited in nature, with prescription being restricted to "exceptional circumstances". This was because full and finalised data from the clinical trials used to support Aptivus's regulatory filing were not yet available. The Commission's most recent approval for Aptivus has effectively removed this clause, suggesting that all the necessary clinical data have been received and evaluated by the European authorities.
Aptivus is a non-peptidic protease inhibitor, which works by blocking the enzyme that assists in replicating the HIV virus. The drug was recently granted full marketing approval by the U.S. FDA (see Germany: 8 October 2007: Boehringer Ingelheim Scoops U.S. FDA Approval for Aptivus Capsules). Both approvals were based on findings from Boehringer's Phase III clinical-trial programme known as RESIST, with the European Commission focusing on the RESIST 1 and RESIST 2 trials. These found that patients experienced a higher level of treatment response with Aptivus and ritonavir compared with rival protease inhibitors combined with ritonavir.
In spite of these results, Aptivus has not been without its critics. The Boehringer drug has come under fire from several organisations due to its price and international marketing strategy (see Germany: 7 September 2005: High-Cost Boehringer Drug Denounced by AIDS Healthcare Foundation and Brazil: 21 January 2008: Boehringer Ingelheim Criticised for Withholding AIDS Drug Aptivus from Brazil). In Italy, for instance, a pack of 120 Aptivus capsules at a strength of 250 mg each is charged at a retail price of 1,269.98 (US$1,977.40) and is not reimbursed. With the dose recommended by the European Medicines Association (EMEA) standing at 500 mg twice a day (1,000 mg or four capsules in all), the purchase of one pack in Italy would only last for 30 days' worth of treatment, making annual consumption of Aptivus prohibitively high.
Potentially even more damaging for the German company, however, was the warning issued by the U.S. FDA in 2006 on several patient fatalities that occurred during clinical trials on Aptivus (see Germany: 3 July 2006: Patient Deaths Reported as FDA and Boehringer Ingelheim Issue Warning on Aptivus). The discovery led to a second safety warning added to Aptivus's existing black-box label—the highest level of caution the FDA can impose on a drug's packaging— in the United States. In Europe, however, the level of caution advised for Aptivus has been decidedly lower and has been limited to the following warnings by the EMEA:
- Aptivus should not be used in people who are hypersensitive (allergic) to tipranavir or other ingredients.
- Use is contraindicated in patients taking rifampicin (for tuberculosis), St John's wort (for depression), or any drug that is broken down by the body in the same way as Aptivus and is harmful at high levels in the blood.
- Patients taking Aptivus may develop lipodystrophy, osteonecrosis or immune reactivation syndrome.
Outlook and Implications
While pricing currently appears to be the biggest challenge facing Aptivus, there are a number of European countries that do offer full subsidisation for the drug, including France, Spain and the United Kingdom. As such, Aptivus may be prescribed more routinely in those markets. For Boehringer, however, HIV/AIDS drugs such as Aptivus are not viewed as money-spinners but as a therapeutic area in which the company is building a reputation for cutting-edge, innovative treatment. Elsewhere in the company's portfolio, new drugs are being approved in more marketable and low-cost treatment areas (see Germany: 28 March 2008: Boehringer Ingelheim's Pradaxa Gains European Approval), while respiratory and cardiovascular drugs are boosting Boehringer's top-line performance (see Germany: 9 April 2008: Boehringer Ingelheim Braces for Key Patent Expiry as 2007 Sales Up 8.8% Y/Y). With regard to Aptivus, however, Boehringer Ingelheim is pursuing follow-on trials from the RESIST programme in order to assess its efficacy in different patient populations, namely specific ethnic groups and children. Results published thus far seem encouraging, and the company may well seek to extend Aptivus's approved indications on both sides of the Atlantic within the next year or two.