ZymoGenetics Inc. opened a broad Phase II program of recombinant human Thrombin (rhThrombin), which is being developed to control bleeding during surgery.
The Seattle-based company began a Phase II study of rhThrombin in patients undergoing liver resection. Three additional Phase II trials are scheduled to begin shortly in patients scheduled for lumbar spine surgery, lower extremity peripheral artery bypass surgery and formation of vascular access grafts for dialysis.
"We see this as not unprecedented, but clearly it is a lucrative opportunity because there is an established market," James Johnson, ZymoGenetics' chief financial officer, told BioWorld Today. "And history has shown that the medical community prefers a recombinant product when one is available."
A bovine-derived thrombin product is used in the U.S., but the company expects the use of rhThrombin to prove a better alternative. Johnson described impurities associated with bovine-derived thrombin, such as small quantities of additional bovine proteins, which can lead to negative immune reactions in patients. The recombinant product can be manufactured to higher levels of purity and consistency.
"Because it's recombinant, and because it's pure human thrombin, we don't expect to see the kinds of reactions that are seen with the bovine product," he said.
But he noted that such a premise remains relatively untested. The four placebo-controlled, double-blinded studies will include 160 patients (40 per study), half with rhThrombin and half with placebo. The endpoints will be safety and time to hemostasis, with a 28-day follow-up to test for development of antibodies to rhThrombin.
ZymoGenetics expects to complete the studies later this year, aiming to begin pivotal Phase III studies early next year. The first of the multicenter Phase II trials follows the completion of enrollment in an open-label Phase I study.
Johnson said he is not aware of competing products in development at other companies, noting that ZymoGenetics' patent position on its recombinant process should provide protection. Its goal is to obtain a label for use of the product as an aid to controlling blood loss in surgery.
The company has a commercial manufacturing agreement with Abbott Park, Ill.-based Abbott Laboratories, which is under contract to produce rhThrombin. Notably, ZymoGenetics said the production of rhThrombin is not dependent on the availability of blood from cattle herds and can be scaled up to meet market demands.
Johnson said ZymoGenetics, which has worldwide rights to the product, plans to internally commercialize rhThrombin.
Elsewhere in its pipeline, the company expects to begin a trial of Factor XIII to evaluate its blood-clotting ability to reduce post-surgery bleeding in cardiopulmonary bypass patients. Outside of ZymoGenetics' products for bleeding, the company is jointly developing a product called TACI-Ig in concert with Geneva-based Serono SA. A Phase I trial in healthy volunteers has concluded, with a trial in lupus patients expected to begin within the next several months. Another product, IL-21, received clearance to enter Phase I studies for malignant melanoma and renal-cell carcinoma.
"We have, in essence, a history in blood-clotting and hemostasis products," Johnson said. "But beyond the thrombin product and Factor XIII, we're pursuing a pretty broad portfolio of genomics-derived products."
ZymoGenetics' stock (NASDAQ:ZGEN) gained 59 cents Monday to close at $16.74.