By Mary Welch
Genzyme Corp. won FDA approval for Thyrogen, its injectable cancer-screening drug, and disclosed an unrelated, potential $31 million deal with Dyax Corp. to develop EPI-KAL2, Dyax's protein for chronic inflammation.
Marketing of injectable Thyrogen - which allows for screening of thyroid cancer patients without unpleasant side effects common to the full-body, radioactive iodine method - will begin immediately by Knoll Pharmaceutical Co., of Mount Olive, N.J., which also manufactures and markets Synthroid (levothyroxine sodium), the leading thyroid replacement therapy in the U.S., said Bo Piela, spokesman for Cambridge, Mass.-based Genzyme.
The deal for EPI-KAL2 with Dyax, also of Cambridge, "is important to us because it brings an early-stage product into our pipeline and it is consistent with our focus on developing treatments for genetic diseases," said Piela.
EPI-KAL2 is a recombinant protein that mimics the effect of a natural inhibitor of C1-esterase and kallikrein. Deficiency of the inhibitor can cause hereditary angioedema (HAE), which causes inflammation and severe pain in respiratory and abdominal tissues. The drug is in preclinical studies. Dyax expects to get toxicity results next year and file an investigational new drug (IND) application in early 2000.
Under the terms of the deal, Genzyme made a $3 million equity investment in Dyax's recent private placement and extended a $3 million line of credit. In addition, it committed $25 million in potential milestone payments. Dyax will handle the clinical development of EPI-KAL2, while Genzyme will assume sales and marketing duties. If the product reaches the market, revenues will be split evenly.
Keith Ehrlich, chief financial officer for privately held Dyax, said the pact is significant "because of Genzyme's deep history and experience in developing, manufacturing and marketing successfully genetic-disease-based products. There is a lot of value in being able to draw on their experience in getting an orphan drug status and registering it worldwide, as well as dealing with reimbursers."
Although the drug is intended for the umbrella problem of chronic inflammation, its initial target is HAE, which afflicts between one in 10,000 and one in 50,000 people worldwide. Shirish Hirani, senior vice president of product development for Dyax, said the company also believes the drug "could be developed for other indications, such as rheumatoid arthritis and inflammatory bowel disease."
Thyrogen Approved For Broad Group Of Patients
Genzyme's approved drug, Thyrogen, will be used in follow-up screening of patients who have been treated for thyroid cancer. Under the FDA-approved label, physicians can use Thyrogen for a broad group of thyroid cancer patients. Serum thyroglobulin testing and radioiodine imaging are the two diagnostic procedures most commonly used with patients being examined for remnant thyroid tissue, thyroid cancer recurrence or metastases.
Full-body radioactive iodine screening requires that patients stop taking their synthetic hormone supplements for three weeks prior to testing, in order to elevate their levels of thyroid stimulating hormone (TSH). This procedure requires patients have elevated levels of TSH in order for any metastasis to take up the iodine. TSH also causes thyroid tissue to release a protein called thyroglobulin, which is measured by a blood test.
But the hormone withdrawal can lead to hypothyroidism, with its symptoms of fatigue, weight gain, constipation, mental dullness, lethargy and depression. Often, the withdrawal's effects prompt patients to forgo screening.
Thyrogen, a recombinant TSH, provides a patient with elevated levels of TSH while still taking hormone supplements, thus avoiding the side effects. In Phase III tests, Thyrogen's side effects were nausea, headaches and vomiting, but these were transient and mild to moderate in severity.
Genzyme expects worldwide sales of Thyrogen will total between $50 million and $75 million, said Piela. In the U.S., physicians order about 135,000 thyroglobulin tests and 25,000 radioiodine imaging whole body scans each year.
Thyrogen's is the fourth new drug application approval for the company, Piela said. Genzyme's first marketed drug, Ceredase, for Gaucher's disease, was replaced by Cerezyme, a recombinant form of Ceredase, in 1994. The company's other approved drug is Renagel (sevelamer hydrochloride), which received the FDA's nod of approval earlier this month for patients with end-stage renal disease. Genzyme's partner for Renagel is GelTex Pharmaceuticals Inc., of Waltham, Mass.
Genzyme's stock (NASDAQ:GENZ) closed Tuesday at $41.50, down $0.562. n