Aventis Retains Revasc; Refludan Divestment Ordered By FTC

Aventis' Refludan is available for licensing through the New York City investment banking company Ferghana Partners as a result of an Aug. 25 Federal Trade Commission order.

FTC appointed Ferghana as a trustee to divest the direct thrombin inhibitor Refludan (lepirudin) after Aventis failed to complete the divestment of Revasc (desirudin) within the six-month period specified in a January consent order authorizing the Hoechst/Rhone-Poulenc merger.

In the original antitrust review, Aventis opted to retain Refludan, which was the first direct thrombin inhibitor approved in the U.S. and was the result of an internal development effort by Hoechst Marion Roussel. Revasc is not yet approved in the U.S., and was licensed by Rhone-Poulenc Rorer from Novartis.

The January consent order authorized FTC to order the divestiture of Revasc or Refludan if Aventis failed to divest Revasc (¹ (Also see "Aventis Merger Would Require Revasc Divestiture; Novartis Has First Rights" - Pink Sheet, 13 Dec, 1999.)).

FTC's choice of Refludan for divestment reflects the commission's analysis of the quickest route to meeting its goal of restoring competition in the direct thrombin inhibitor market. Aventis will be required to supply Refludan to the eventual licensee at cost for four years.

Aventis may see retaining Revasc as the more attractive outcome given the developments in the market since the January order.

In May, an expanded indication for Refludan - use in acute coronary syndrome - was rejected by FDA's Cardiovascular & Renal Drugs Advisory Committee (² (Also see "Refludan Coronary Syndrome Use Not Supported By Heparin-Placebo Data" - Pink Sheet, 8 May, 2000.)). Refludan is approved for anticoagulation in patients with heparin-induced thrombocytopenia.

Aventis' sNDA for broader labeling was based on two clinical trials that failed to meet the primary endpoint of superiority to heparin. The company argued that the indication could still be approved based on an extrapolation of historical data comparing heparin and placebo, but the committee and FDA disagreed.

Refludan is also facing new competition in the U.S.: SmithKline Beecham/Texas Biotechnology's argatroban cleared FDA June 30 for HIT (³ (Also see "SmithKline Argatroban Detailing To Encourage Early Identification Of HIT" - Pink Sheet, 10 Jul, 2000.)).

Another direct thrombin inhibitor, The Medicines Company's Angiomax (bivalirudin), could be available as early as mid-2001 for use in angioplasty if TMC can complete the final stages of a protracted FDA review (⁴ (Also see "TMC Angiomax Launch Projected For Mid-2001 With Innovex Sales Force" - Pink Sheet, 14 Aug, 2000.)).

Aventis filed an NDA for Revasc in June for prevention of deep vein thrombosis in hip replacement surgery. The filing date suggests a mid-2001 launch, assuming an uneventful FDA review.

The DVT market is one of Aventis' core therapeutic categories. The company's Lovenox (enoxaparin) posted worldwide sales of more than $400 mil. for the first half of 2000, up more than 30%.

Revasc was approved in Europe in 1997 for prevention of deep vein thrombosis in hip and knee replacement surgery. In approving the drug, European regulators explicitly concluded that Revasc showed superior efficacy to heparin and to Lovenox.

Revasc's commercial performance overseas has not been exceptional, as neither Aventis nor Novartis lists the products among significant contributors.

Under the January consent order, Aventis was required to offer Revasc back to Novartis at no cost. Novartis' decision not to take the product back suggests that the Swiss company believed it was unlikely to find as attractive terms in a contract with another partner, or through marketing Revasc on its own.

The appointment of a trustee to divest Refludan has no bearing on whether FTC will seek civil penalties against Aventis for failing to divest Revasc. The Revasc divestment efforts were overseen by an interim trustee who reported back to FTC, so the commission has a full record on which to base a decision about whether Aventis made a good faith effort to comply with the order.

Aventis is facing an FTC action stemming from its settlement of generic drug litigation against Andrx.