 Emisphere's Oral Heparin,
ELAPRIN®
In 2000, we evaluated an oral heparin solution formulation in a Phase III clinical study called PROTECT. The study demonstrated that heparin delivered by the oral route using Emisphere’s eligen® oral delivery technology was absorbed and exhibited a biological effect and that the EMISPHERE delivery agent used to deliver the heparin was safe. Since then, we have focused our efforts on developing a solid dosage formulation of oral heparin that favorably compares to the solution formulation that we evaluated in the Phase III study.In 2004,
further development efforts culminated in the testing of a soft-gel capsule formulation of heparin, ELAPRIN®. The formulation demonstrated pharmacodynamic responses in healthy volunteers that were substantially higher than those obtained following oral administration of the PROTECT solution formulation (as measured by anti-factor Xa, anti-factor IIa, and aPTT markers) and contains less heparin and SNAC per dose compared to the oral solution formulation.
The new Phase III study, that has been reviewed and
accepted by the FDA, will be a randomized, double
blind, double-dummy, multi-center study in
approximately 2100 patients to determine the safety
and efficacy of ELAPRIN® (heparin
sodium, usp) soft gelatin capsules versus Warfarin
sodium for the prevention of venous thromboembolism
following elective total hip replacement.
The primary clinical endpoint to the study will
compare the incidence of the composite endpoint of
VTE and death within 30 days randomized to receive
ELAPRIN® (heparin sodium, USP) Soft
Gelatin Capsules versus those randomized to receive
Warfarin sodium. VTE is defined as all proximal DVT,
symptomatic distal DVT, PE and death due to PE.
The FDA has agreed to permit Emisphere to use
ultrasound, which is a routinely performed
non-invasive procedure, as the method of detection
of proximal DVT’s instead of venography, which is a
rarely performed and an invasive procedure. Use of
ultrasound will permit a faster enrollment process.
The safety database from the Protect study is usable
for product registration.
Emisphere hopes to initiate the Phase III trial
during the second half of 2007.
Current Uses
Currently, the most common indication for heparin therapy is the prevention of blood clot formation following major surgical procedures lasting longer than 30 minutes (e.g., orthopedic, pelvic, abdominal, trauma, angioplasty or heart surgery). A variety of LMWH products are indicated for prevention of deep venous thrombosis (DVT) after hip or knee-replacement surgery, for patients undergoing abdominal surgery, and for patients who are at risk for DVT or pulmonary embolism (PE) formation due to severely restricted mobility.
According to the National Center for Health Statistics, there are more than a million hip and knee replacement surgeries performed in the U.S. each year, putting patients at risk for DVT. Unfortunately,more than 50,000 fatal cases of DVT are reported each year. Current prophylactic treatment of DVT generally consists of approximately one to two weeks of injectable LMWH or 6 weeks of the anti-vitamin K oral anticoagulant, warfarin (COUMADIN®). Generally, physicians prefer heparin over warfarin because heparin has a rapid onset of anti-coagulant activity, a short physiological half-life and significantly fewer incidences of drug-drug interactions. These pharmacological properties facilitate dose adjustment and contribute to Heparin’s relatively large margin of safety.
Market Opportunity
Currently, worldwide heparin sales are estimated to be more than $4 billion, with a 15% yearly growth rate. The annual global market for anticoagulant therapies is approximately $6 billion.
Recent clinical studies indicate that heparin’s
clinical benefits may extend beyond its
anticoagulant properties. This could further expand
the market potential. The major disadvantage of
heparin therapy is the requirement for parenteral
administration, with the associated patient
discomfort, lack of compliance and required extended
hospital stays. We believe that successful
development of an oral heparin formulation would
reduce patient discomfort and increase patient
compliance and allow physicians to prescribe heparin
therapy for use in an outpatient setting,
potentially expanding heparin’s already substantial
market base.
About Heparin
Unfractionated heparin is a large heterogenous molecule with a molecular weight that can range from 5,000 to 30,000 daltons. Low molecular weight heparins such as dalteparin, enoxaparin and tinzaparin range from 1,000 to 10, 000 daltons.
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