By Debbie Strickland

Genzyme Corp.'s recombinant thyroid stimulating hormone, Thyrogen, has passed a second Phase III test and appears ready to graduate to New Drug Application status.

Thyrogen's market potential is $75 million annually, which could boost revenues at the Cambridge, Mass., company by more than 10 percent. In 1996, Genzyme reported revenues of $511.4 million.

Release of the Phase III results was withheld until after the close of trading. Shares of Genzyme (NASDAQ:GENZ) ended Wednesday at $22.75, down $0.375.

"This study verifies what we've shown in the first Phase III trial in a much more robust and vigorous fashion," said E. Chester Ridgway, professor of medicine and head of the division of endocrinology at the University of Colorado Health Science Center. He served as one of the trial's principal investigators.

"The results suggest that Thyrogen will have a place in the physicians' armamentarium for the treatment of thyroid cancer," he added. "It will allow us to manage the disease without subjecting patients to the debilitating hypothyroid effects associated with thyroid hormone removal."

Thyrogen boosts bloodstream levels of thyroid stimulating hormone (TSH). Patients who have had thyroid cancer -- the standard treatment for which is removing the thyroid gland -- must boost their bloodstream level of TSH by several fold prior to annual or biannual screens for cancer recurrence.

The conventional method for elevating TSH is to take patients who have had their thyroid glands removed off their synthetic hormone supplement three weeks prior to testing. That method works, but patients develop symptoms of hypothyroidism, including fatigue, weight gain, constipation, mental dullness, lethargy and depression.

With Thyrogen, patients continue taking hormone supplements, thus avoiding these symptoms.

Data from the trial showed that Thyrogen produced scans that were equivalent to scans produced after withdrawing patients from thyroid hormone supplements in 92 percent and 93 percent of patients, depending on which of two dosing regimens was used.

In a previous Phase III trial, completed in 1994, the treatment produced scans equivalent to withdrawal scans in 86 percent of patients.

Henri Termeer, Genzyme's chairman and CEO, said the latest trial produced a "strong, positive outcome," allowing the company to apply for marketing approval in the U.S., Europe and Canada.

Genzyme expects this year to submit a New Drug Application to the FDA and an application for regulatory approval in Europe. A Canadian application for approval will likely come in 1998.

The 220-patient Thyrogen trial was conducted in 11 U.S. and three European centers. In each patient, researchers performed a radioiodine whole-body scan following Thyrogen administration and a second scan following thyroid hormone withdrawal. A panel of three nuclear medicine experts rated the scans. Blood samples were also collected following Thyrogen administration for measurement of serum thyroglobulin.

Two dosing regimens were tried: arm I, 0.9 mg per day for two days; and arm II, 0.9 mg every 72 hours over a seven-day period. The first group's scans were equivalent to hormone withdrawal in 92 percent of cases, the second in 93 percent.

Among the 113 patients in arm I, nine withdrawal scans were rated better than Thyrogen scans, while three Thyrogen scans were rated better than withdrawal. In arm II, which contained 107 patients, eight withdrawal scans were rated better than Thyrogen and five Thyrogen scans were rated better than withdrawal.

The company has not yet completed analysis on Thyrogen's effect on the sensitivity of thyroglobulin testing.

Two quality of life measures were unchanged following Thyrogen administration, but were significantly reduced following hormone withdrawal.

Hormone withdrawal increased to a highly significant degree -- 14 hypothyroid symptoms as measured by the Billewicz Scale.

The second instrument used in the trial, the SF-36 Health Survey, is a general measure of quality of life that assesses a person's functional status and well being. There were highly significant differences in the scores before and after hormone withdrawal on the measures of the scale related to problems with performing physical and work activities.

Some patients did, however, experience adverse events while on Thyrogen. Nine percent reported headaches, 6 percent reported nausea and 4 percent experienced vomiting. The company described these events as "transient and mostly mild or moderate in severity." *