By Mary Welch
Emisphere Technologies Inc. finalized the Phase III protocol for its oral liquid heparin formulation for the prevention of deep vein thrombosis (DVT), with the trial expected to start enrollment and dosing by the end of the year.
The trial will be a randomized three-arm study and will take place at 95 sites in the U.S., Canada and the UK. The Tarrytown, N.Y., company will choose the optimal dose from the first trial and then conduct a second trial sequentially.
In total, some 3,000 patients will be treated with more than 90,000 patient exposure days. The Canadian and UK sites should start enrolling patients in February. The company expects to submit a new drug application in the third or fourth quarter of 2001, with launch early in 2002.
¿The FDA was very helpful, but we were all pretty much on the same track,¿ said Barry Kanarek, Emisphere¿s senior vice president of clinical and regulatory affairs and chief medical officer. ¿The only real difference between the Phase III trials and the Phase II are in the comparator and the duration of dosing.¿
The upcoming Phase III trials will pit the oral heparin against injectable enoxaparin (Lovenox), while the Phase II trials compared oral heparin formulations to injectable heparin
¿In our Phase II program, we compared the safety and efficacy of oral heparin to that of subcutaneous injectable heparin,¿ Kanarek said. ¿Heparin has been in use since 1916. The primary objective in this trial was not only to demonstrate comparable safety and efficacy to the comparator, but also to confirm what we already suspected, that oral heparin is equal to injectable heparin based on clinical endpoints.¿
In its extensive Phase I program, the company clearly demonstrated this as well as its ability to deliver oral heparin based on laboratory or surrogate endpoints, he said. ¿We know from previous trials where thousands of patients had been treated with the same parameters that we used, that again oral heparin equals low molecular weight heparin in its actions.¿
For the Phase III program Emisphere is comparing oral heparin to what is considered to be the current standard of care, Lovenox, he said. ¿It is our intent to demonstrate that by substituting oral heparin in an extended prophylaxis regimen that we will clearly demonstrate superiority over Lovenox.¿
In the upcoming Phase III trial the oral heparin will be dosed for 30 days following surgery, compared to 10 days of Lovenox following total hip replacement surgery. The primary endpoint will be the occurrence of DVT during the treatment phase.
Heparin is an anticoagulant, antithrombotic compound that is prescribed for a variety of cardiovascular indications, including DVT. Thirty percent to 50 percent of all patients who undergo hip replacement and knee replacement surgeries will develop DVT without preventive treatment. DVT can lead to life-threatening pulmonary embolisms and death.
In addition to setting its Phase III protocol, the company also released its first-quarter 2000 figures.
The company¿s quarter, which ended Oct. 31, was also the first that reflected its restructured deal with Elan Corp. plc, of Dublin, Ireland. Earlier this year, Emisphere took back all rights to develop and market the oral heparin form, while Elan maintained a financial interest in the product¿s success. As part of the deal, Emisphere issued Elan a $20 million zero-coupon note. The note, payable in seven years, has an interest rate of 15 percent annually. (See BioWorld Today, July 7, 1999, p. 1.)
¿This is the first quarter where it shows up on our P&L (profit and loss) statement of about $900,000 to $1 million per quarter related to it,¿ said Charles Abdalian, the company¿s chief financial officer. ¿But it¿s a non-cash notation so it makes the numbers look a little meaner than they would be if it were on a cash basis.¿
The company reported contract revenues for the quarter of $625,000, compared to $3.6 million in the same period for fiscal 1999. Part of the discrepancy came from $2.7 million in revenues from the company¿s former heparin joint venture with Elan and research and development funding from Eli Lilly & Co., of Indianapolis, Ind., which ended in the third quarter of fiscal 1999.
The company reported a quarterly loss of $9.9 million, or 81 cents per share, compared to a net loss of $3 million the first quarter of fiscal 1999.
Emisphere¿s stock (NASDAQ:EMIS) closed Wednesday at $19.312, down 56.25 cents.