By Mary Welch

Thymoglobulin, SangStat's drug for acute kidney rejection in transplant patients, won approval from the FDA.

Menlo Park, Calif.-based SangStat's oral cyclosporine product, SangCya, was approved last October for prevention of solid organ transplant rejection. (See BioWorld Today, Nov. 4, 1998, p. 3.)

"Relative to the approval of SangCya, [Thymoglobulin's] approval is not as significant, but clearly it adds to SangStat's franchise as a transplant medical company," said William Tanner, an analyst with Vector Securities International Inc., of Chicago. "But Thymoglobulin is clearly effective, and we believe it will be widely used for acute rejection."

The FDA nod came following Phase III results showing that Thymoglobulin, a polyclonal antibody, successfully reversed acute organ rejection in 78 percent of 163 kidney transplant patients, compared with 67.5 percent for patients treated with Atgam, which is marketed by Pharmacia & Upjohn Inc., of Bridgewater, N.J. Patients treated with Thymoglobulin had a graft survival of 83 percent and patient survival of 93 percent one year later.

"[Thymoglobulin] will probably be the predominant drug in its class, and has shown itself to be the superior drug to Atgam," Tanner said. "But it also has a lot more upside potential if it is used for induction therapy."

Thymoglobulin is manufactured by Pasteur Merieux Serums & Vaccins, of Lyon, France.

Sales Projected To Hit $56M By 2002

Tanner estimated sales of Thymoglobulin will reach $15 million, $32 million, $46 million and $56 million in 1999 through 2002, respectively. However, if the drug is used for induction therapy - which prevents organ rejection immediately following transplantation - revenues could easily exceed $100 million a year in this U.S. alone, he said.

Jean-Jacques Bienaime, chief operating officer of SangStat, would not disclose in-house projected sales figures, but acknowledged that Tanner's numbers are on target. The potential market is $85 million in the U.S., Bienaime said.

Thymoglobulin, a pasteurized anti-thymocyte rabbit immunoglobulin, induces immunosuppression as a result of T cell depletion. Thymoglobulin is made up of a variety of antibodies that recognize key receptors on T-cells, the cells of a transplant recipient's immune system that recognize and ultimately reject foreign objects - such as a transplant. The exact mechanism is unknown, but researchers believe Thymoglobulin antibodies may inactivate and kill these T-cells, thus reversing the rejection process. Side effects include fever, infections and thrombocytopenia.

The injected drug is expected to be available within four to six weeks. The labeling will not carry claims of superiority over Atgam or any other drug, because only one pivotal trial was done. The FDA requires more than one pivotal trial to justify such superiority claims, Bienaime said.

"However, results of the pivotal study were published, and the differences based on primary endpoints were very significant," he said. "The transplant community is small. There are 250 centers, and 28 centers participated in the study. In addition, 145 patients are being treated on a compassionate basis, and those doctors know it's more effective."

The prices will be comparable to Atgam's, which are between $5,000 to $10,000 per treatment period, and can last anywhere from seven to 14 days.

Between 20 percent and 60 percent of the 12,000 Americans who receive kidney transplants each year experience acute rejection during the first year following transplantation, and the rejection often leads to the loss of the transplanted organ. Acute rejection is one of the most significant risk factors in determining the success of a new organ and the recipient's chances of survival.

The double-blinded, randomized, multicenter Phase III trial took place with kidney transplant recipients who experienced an acute graft rejection episode. One hundred and sixty-three patients were given either 1.5 milligrams per kilogram of body weight per day of Thymoglobulin or 15 milligrams per kilogram per day of Atgam for seven to 14 days and then followed for a year. The successful reversal of rejection is defined as improvement of renal function (measured by serum creatinine level), and survival of the graft one month after the end of therapy.

SangStat intends to pursue the induction therapy indication and this year will start a one-on-one trial of Thymoglobulin versus Simulect (basiliximab), an immunosuppressive agent marketed by Novartis AG, of Basel, Switzerland. Simulect was approved by the FDA last May. Results of the comparison trial are expected by year's end, with marketing filing by the first quarter of 2000.

Another monoclonal antibody that, like Simulect, binds to the alpha subunit of the interleukin-2 receptor is Zenapax (daclizumab), marketed by Hoffmann-LaRoche Inc., of Nutley, N.J., and Protein Design Labs Inc., of Mountain View, Calif. Zenapax received FDA approval late in 1997. (See BioWorld Today, Dec. 12, 1997, p. 1, and May 14, 1998 p. 2.)

"We believe that Thymoglobulin will prove more effective than Atgam, Simulect and Zenapax when used for induction setting in kidney transplant patients," Bienaime said. "We've already done one study against Atgam for this, and the incidence of biopsy-proven acute rejection was 4.2 percent for Thymoglobulin versus 24 percent for patients given Atgam. We also believe we will be much more effective in patients with moderate to high risk."

Bienaime To Take CEO Post As Pouletty Steps Aside

SangStat also disclosed its founder, Philippe Pouletty, current chairman and CEO, will step down as CEO but remain as chairman. Bienaime will move into the CEO chair. Prior to joining SangStat six months ago, Bienaime was senior vice president of corporate marketing and business development with Rhone Poulenc Rorer Inc., of Collegeville, Pa.

Tanner said he believes Bienaime's promotion is a plus for the company.

"SangStat is moving from a developmental company to a firm with commercial products and Jean-Jacques has more experience in that field," he said. "But it is also good that [Pouletty] is staying on. He's an excellent physician and will be very useful in strategic planning, acquisitions and pipeline-filling."

Bienaime said Pouletty will "remain active" in the company.

SangStat's stock (NASDAQ:SANG) closed Tuesday at $27.562, up $4.812. n