Staff Writer

The stock-boosting special protocol assessment disclosed Monday for a trial with Keryx Biopharmaceuticals Inc.'s multiple myeloma drug perifosine could be the trigger for serious partnership talks, as the firm now has two Phase III-ready compounds.

"We did wait for this inflection point," said Ron Bentsur, CEO of New York-based Keryx, which has a market cap of only about $79 million, despite the pair of late-stage drugs. "There've been some cordial meetings here and there, but we haven't really gone out and pounded the pavement."

Perifosine is licensed to Keryx in the U.S., Canada and Mexico, while Aeterna Zentaris Inc., of Quebec City, owns rest of the world rights. On word of the SPA, Keryx's shares (NASDAQ:KERX) closed at $1.61, up 46 cents, or 40 percent.

"The jump is nice to see, and we're very happy about it," Bentsur allowed, but said Keryx still is undervalued and thus ripe for partner plucking.

Perifosine will be tested in a 400-patient, double-blind, placebo-controlled study against relapsed or relapsed/refractory MM who have been treated with Velcade (bortezomib), from Takeda subsidiary Millennium Inc. Trial subjects will get a three-drug combo - Velcade, dexamethasone and perifosine - or placebo.

The study has a primary endpoint of progression-free survival, "something we felt we needed to lock into an SPA," Bentsur said. The more arduous and harder-to-prove overall survival is one of the secondary endpoints, along with overall response rate and safety.

First-line MM patients typically get Velcade, Revlimid (lenalidomide, Celgene Corp.), or Thalomid (thalidomide, also Celgene), all given with dexamethasone. Responders often go on to a stem cell transplant, then back to a similar drug regimen. Those who are not eligible for a transplant or who don't respond may get prednisone.

Sicker, more desperate third-line patients - the segment targeted by perifosine, an inhibitor of the PI3K/Akt pathway - sometimes are given Revlimid/dexamethasone plus an investigational drug, or Velcade/dexamethasone along with Doxil (doxorubicin, Johnson & Johnson).

"Beyond that, most patients go to clinical trials," Bentsur said, and now they have Keryx's as a possible choice.

In the Phase I/II trial with perifosine, the average number of previous lines of therapy for patients enrolled was five. The Phase III study only allows patients with as many as four lines of previous therapy, and all patients must have been exposed to Velcade and Revlimid at some point in the course of their treatment.

About 20,000 new MM cases are diagnosed yearly in the U.S., and all eventually worsen. Bentsur said the fact that a mix of rotating third-line therapies is available will not hurt Keryx's partnering chances.

"If you look at cancer therapies nowadays, a lot of them are going after these end-stage, relapsed/refractory populations - that's the shortest route to approval," he said, pointing again to the PFS primary endpoint in the Phase III trial. "The bar is lowest because you're going after patients who are very advanced. You don't have to [run trials] head-to-head against drugs that you know are pretty efficacious in first line."

Earlier this summer at the American Society of Clinical Oncology, Keryx reported positive Phase II results with perifosine in advanced metastatic colon cancer and advanced kidney cancer, causing shares to soar by 74 percent. (See BioWorld Today, June 2, 2009.)

The company also has Zerenex (ferric citrate), an oral, iron-based compound that binds to phosphate and forms nonabsorbable complexes. Zerenex has completed Phase II work for hyperphosphatemia in patients with end-stage renal disease, and the drug is partnered in Japan with Japan Tobacco Inc. and Torii Pharmaceutical Co. Ltd.

No Comments