The clock is ticking on key decisions related to a pair of drugs for myelodysplastic syndrome (MDS) - MGI Pharma Inc.'s Dacogen and Celgene Corp.'s Revlimid - and the market seems ready to widen, even as physicians continue to look fondly upon Pharmion Corp.'s injectable Vidaza (azacitidine), the compound in-licensed from Pharmacia & Upjohn Co., now part of Pfizer Inc.
Meanwhile, erythropoietin-stimulating proteins such as Epogen (epoetin alfa) and Aranesp (darbepoetin alfa) from Amgen Inc. hold their ground as front-line therapies for anemia, which typically crops up as a complication of MDS.
MDS, which consists of five diseases regarded as precursors to leukemia, can be caused by chemotherapy, radiation, viral infection or a genetic flaw. The symptoms are anemia, with weakness, fatigue, frequent infections, easy bruising, bleeding, fever, weight loss and a sense of feeling full.
Officially classed as a disease in 1976, MDS was first believed to cause about 1,500 new cases every year, but numbers have proved to be much higher, possibly because of more precise methods of diagnosis. About 7,000 to 12,000 new cases are pegged annually in the U.S., mainly in people older than 60.
MGI's Dacogen (decitabine) has a PDUFA date of Sept. 1, and an FDA panel is expected to review the new drug application for Celgene's Revlimid, a derivative of Thalomid, the company's brand name for thalidomide, on Sept. 14.
Last fall, investors were buzzing about the ripeness of Celgene for a takeover bid: The firm had reached profitability in 2003, its stock had jumped more than 25 percent since the start of 2004, the FDA was reviewing Thalomid for blood cancer, and shareholders were in line for a 2-for-1 stock split. (See BioWorld Financial Watch, Sept. 20, 2004.)
The takeover didn't happen, but there was July activity in the MDS/cancer landscape - and it was a move that might have come as a surprise to some observers. MGI, which also markets the anti-nausea drug Aloxi (palonosetron hydrochloride) for chemotherapy patients, disclosed its plan to buy out Guilford Pharmaceuticals Inc. for $177.5 million in cash and stock.
That deal gives MGI Aquavan, Guilford's Phase III candidate for procedural sedation, as well as Gliadel, the marketed product for malignant gliomas and recurrent glioblastoma multiforme (brain cancer). Also in the pipeline, Guilford has N-acetylated(alpha)-linked acidic dipeptidase for chemotherapy-induced neuropathy and poly(ADP-ribose) polymerase, a chemotherapy or radiation therapy sensitizer.
There's more. Guilford also has Saforis, an oral formulation of L-glutamine to reduce oral mucositis in patients getting anthracycline-based chemotherapy, and a new drug application for that product is expected in the third quarter. Also last fall, MGI entered a marketing deal with SuperGen Inc. for Dacogen, and disclosed plans at the same time to buy Aesgen Inc. for $32 million and Zycos Inc. for $50 million. Saforis came from Aesgen.
MGI's own Aloxi has a bright future, too. In 2003, MGI agreed to pay at least $22.5 million to Helsinn Healthcare SA for rights to the product in post-operative nausea and vomiting, making the fit with Guilford better, though not everyone saw as much right away.
"We suspect the jury will be out on the full wisdom of this transaction until a clearer picture of Aquavan's clinical utility emerges next year," wrote Christopher Raymond, analyst with Robert Baird & Co., in a research report. Raymond favored the deal after "much consideration."
To get Aloxi used for its post-operative indication, MGI needs a hospital presence and Guilford has that, thanks to Gliadel. But the path for Guilford's Aquavan - the water-soluble prodrug of propofol, acquired through the firm's $7 million buyout of ProQuest Pharmaceuticals Inc. late last year - has not been altogether smooth.
In March, Guilford said adjustments in its voluntarily suspended Phase III study with the drug would extend only "modestly" the time to filing a new drug application, but the firm's stock fell by more than a third.
Aquavan had met its primary efficacy endpoint with no serious adverse events. Investigators compared the compound with midazolam for sedation of patients undergoing colonoscopy. Sedation success with Aquavan was 96 percent, with deeper levels of sedation for longer periods compared to patients who got midazolam, though there also was a higher level of adverse events in the Aquavan patients. They ended up showing a median time of two minutes to sedation and a median time of 11 minutes to full recovery from the end of the procedure.
In April, Guilford restarted the Aquavan program after FDA talks. The company reduced the number of clinical trials from 13 to five, including a dose-ranging study in colonoscopy. Based on those findings, Guilford is planning two pivotal trials, one in colonoscopy and the other in minor surgical procedures, with an NDA possible in the second half of next year.
As it takes over Guilford, MGI is aiming at MDS with Dacogen. Raymond noted while two-thirds of MDS patients are first diagnosed as low-risk, the most common intervention - given to about half of high-risk patients and 20 percent of low-risk patients - is treatment of anemia with an EPO agent.
For high-risk patients not getting EPO, Vidaza is the leader, with almost 80 percent of physicians reporting in a Baird survey that they have used the drug alone or in combination with Thalomid or Trisenox (arsenic trioxide), the leukemia drug from Cell Therapeutics Inc. Trisenox recently was sold to Cephalon Inc. in a deal worth up to $170 million. In low-risk patients, about one-third of physicians prescribe Vidaza and another third prescribe Thalomid with another 10 percent prescribing the two in combination.
Baird reported that doctors increasingly favor Vidaza though the drug's overall penetration still is only 20 percent. Revlimid is "clearly top of mind" with Dacogen coming in well behind. MGI, though, was upbeat about the Guilford buyout and prospects generally, with Lonnie Moulder telling BioWorld Financial Watch the company is "really well positioned from an oncology standpoint."
Approval of Revlimid and a positive nod from the FDA panel on Dacogen could boost both in the estimation of investors and physicians - and further complicate the shifting MDS landscape. The game is one of wait and watch.