SAN FRANCISCO -- Delivering large proteins orally has long been a brass ring of drug development. But companies have struggled without much success to grab it.
will announce data Monday that it claims at least get it close to grasping the ring. The company will release what it says are promising results in Phase II trials for its liquid form of heparin, a common blood thinner. Emisphere was to discuss the results at an analyst meeting Sunday afternoon ahead of the
Hambrecht & Quist
biotech conference being held here this week.
While it is not a protein, heparin is a large molecule, and the data suggest that the company's oral large-molecule-delivery technology is nearing its promise, the company says. The company is working on several programs to develop oral formulations of proteins, but the heparin project is the lead and most important for investors. The project's success also is important because for many years Emisphere has been widely viewed as long on promise but short on delivery.
"This is a major, major event," Michael Goldberg, the company's CEO and chairman, said in an interview here. "Normally, when we talk about delivering large molecules orally, we are met with snickers and derision and comments like, 'Why don't you call the Psychic Hotline! Can't happen.' This is a quantum leap in the field."
Emisphere, a small Tarrytown, N.Y., biotechnology company, is developing oral heparin with the Irish drug-delivery company
. Now, the companies will embark on a large Phase III trial to prove that this version of heparin is truly as safe and either better or as good as the current injectable forms of the blood thinner. The two companies hope to sign a sizeable deal with a major pharmaceutical company in the next six to nine months for the product, said Goldberg.
The market for heparin worldwide is about $2 billion a year, he said, with about $1.5 billion of that coming from a more convenient form of the drug called low-molecular-weight heparin. But it's all given to patients through injections.
Goldberg is sensitive to Wall Street's skepticism and complaints that the early trials, called Phase I, took longer than anticipated.
"I took a lot of heat for how long I spent in Phase I. But we wanted a very good sense of what we were doing," he said.
The Phase II trial followed 123 patients who had total hip replacements. These patients have a propensity for developing blood clots in their legs that can migrate upward, causing heart attacks. Therefore, they are given a blood thinner. In the study, one group of patients received two teaspoons of Emisphere's liquid form, or 60,000 units, and one group got a tablespoon, or 90,000 units. Both were given the drug three times a day. These doses were compared with the injectable form of the drug, which was given three times a day in 5,000 units each.
According to Goldberg, the number of blood clots, or deep vein thromboses or pulmonary emboli, were comparable in all three groups of patients in the study. The number of patients who had minor or major bleeding was also comparable across all groups. The data also were comparable to historical data on heparin, the CEO said.
The company hopes to start a Phase III trial in the second quarter. Emisphere has not decided whether to do one or two Phase III trials or whether the trials will be designed to show its product is better than standard injectable heparin or simply equivalent. The one trial Elan and Emisphere will definitely do will enroll 2,100 to 2,200 patients and will compare the liquid form to a low-molecular-weight version.
At the same time, however, there may be cracks in the relationship between Emisphere and Elan. In a separate interview, Donal Geaney, Elan's chairman and CEO, suggested the program wasn't vital to the much larger Irish company. He also suggested the product was not as promising as if it were an oral version of the market dominant low-molecular-weight heparin.
"We're not as dependent on the program as Emisphere is," said Geaney, adding, "I personally think the low-molecular stuff seems to be where the industry is concentrating."
He said the program is definitely working, but "we are less enthusiastic about talking about Phase II stuff anyway."
Goldberg sighs. He said that low-molecular-weight heparin has less frequent dosing, and it's that convenience that contributes to its market position. He said of Elan: "They have been a good financial partner, but they haven't committed the effort that we've made to getting an understanding of the market and the
molecule's activity. I'm frustrated that they haven't dedicated resources to getting up to speed on the long-term value of this family of products."
And so even with new data in hand, Emisphere keeps battling the skeptics, even among its allies.