AIDS
Doxil Clinically Beneficial in Kaposi's Sarcoma
By FDA Advisory Committee
Nov 8, 2005, 14:57

The data already submitted to FDA is sufficient to confirm clinical benefit of Johnson & Johnson�s AIDS-related Kaposi�s sarcoma therapy Doxil, the company maintains in briefing documents for the Nov. 8 meeting of FDA�s Oncologic Drugs Advisory Committee.

J&J says it has �given substantial consideration to the conduct of an additional study that might demonstrate clinical benefit of Doxil.�

However, �based on the data previously submitted�and the two recent publications that further support the clinical benefit of Doxil in patients with AIDS-related KS receiving [highly active anti-retroviral therapy] above and beyond the benefits that may be achieved by HAART alone, [J&J] believes that the totality of data presented provide substantial evidence for the clinical benefit of Doxil in AIDS-related KS,� the briefing document states.

�In addition, we believe that it would be difficult, if not impossible, to conduct a further randomized clinical study in patients with AIDS-related KS,� the company adds.

Doxil (doxorubicin) is one of a number of products approved prior to 2002 with unfulfilled accelerated approval commitments that will be reviewed by the panel.

Doxil received accelerated approval in 1995 for treatment of chemotherapy-refractive AIDS related KS. As part of the approval, J&J agreed to conduct a Phase IV trial comparing Doxil to Gilead�s DaunoXome (daunorubicin).

J&J initiated the study (30-38) in 1996 and submitted the results to FDA in 2002. The study found that 80% of doxorubicin patients experienced clinical benefit versus 63% of daunorubicin patients.

Following submission of the results, FDA informed J&J that the advent of HAART in 1996 made it difficult to interpret Doxil�s clinical benefit.

ODAC also met to review unfulfilled accelerated approval trial commitments in March 2003. Following the meeting, J&J agreed to conduct a reanalysis of the 30-38 study, evaluating �confirmed tumor response among patients who had not experienced changes in their anti-retroviral treatment from 60 days prior to study treatment until first response was observed,� the briefing document says.

According to J&J, the �reanalysis showed that confirmed tumor response was 50% or 55% irrespective� of whether patients were in the stable anti-retroviral therapy population or the overall trial population.

However, �FDA subsequently (29 March 2005) indicated to the sponsor that the interpretation of these results was still confounded by changes in HAART,� prompting J&J to withdraw the sNDA for full approval.

In addition to study 30-38, J&J cites Spanish and German studies examining concomitant use of Doxil and HAART as evidence of the agent�s clinical benefit.

In addition to Doxil, the committee will review Genzyme�s Campath, Pfizer�s Celebrex, SkyePharma�s DepoCyt, MedImmune�s Ethyol, Wyeth�s Mylotarg and Seragen�s Ontak during the Nov. 8 meeting.

Virtually all of the products appeared before the panel during its 2003 review of accelerated approval commitments. As was the case in 2003, sponsors are citing patient accrual difficulties as the main challenge to completing the confirmatory trials.

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