At the start of the month, Pharmion Corp. said the European Medicines Agency accepted for review its application for Thalidomide Pharmion, its therapy for untreated multiple myeloma that was licensed from Celgene Corp. (which markets the product as Thalomid in the U.S.).
Good news, and Pharmion's shares - which have been sinking since February, after a steady, two-month spike - could use a boost. But even more encouraging might be the results from a physician survey by Lazard Capital Markets, showing that uptake of amrubicin for small cell lung cancer might be stronger than many expected. Much stronger.
Pharmion gained the anthracycline amrubicin in November as part of the $55 million net-of-cash buyout of privately held Cabrellis Pharmaceuticals Inc. for $59 million up front, with $12.5 million due each for approvals of amrubicin in the U.S. and the European Union. If the drug is cleared for a second indication in the U.S. or overseas, Pharmion would make another payment of $10 million for each market.
Nippon Kayaku Co. Ltd. markets amrubicin under the trade name Calsed in Japan, where the drug (originally developed by Dainippon Sumitomo Pharmaceuticals Co. Ltd.) won approval in 2002 for non-small cell lung cancer and SCLC. Cabrellis, known as Conforma Therapeutics Corp. before Biogen Idec Inc. bought Conforma in May 2006, licensed North American and European Union rights in June 2005.
Amrubicin is the first totally synthetic anthracycline in the widely used class, which let Dainippon scientists tweak the drug to distinguish it from the likes of doxorubicin, daunorubicin and epirubicin, particularly in the lack of cumulative toxicity. NSCLC will be the next indication sought in the U.S.
Meanwhile, in SCLC, the Lazard survey of 30 oncologists who treat more than 100 lung cancer per month has turned up some surprising results: an average projected adoption rate of 53 percent in front-line SCLC patients with extensive disease, and 57 percent as a second-line agent, as compared with Lazard's top-end estimates of 2 percent in front-line and 6 percent in second-line.
The findings caused Lazard to boost sales estimates from $50 million to $66 million during the first year of launch, expected in 2011, and to hike the number of patients treated with the compound from 1,500 to 3,800 in the U.S. and Europe.
Lazard also halved its projected yearly cost of amrubicin therapy to $10,000, based on an analysis indicating a yearly cost of therapy for Hycamtin (topotecan), the topoisomerase I inhibitor approved from GlaxoSmithKline plc for relapsed SCLC and relapsed ovarian cancer. Even so, amrubicin sales could hit $136 million if physician enthusiasm matches the poll.
Data from several ongoing Phase II studies with amrubicin are due in the fall of this year, and the Phase III registration trial in relapsed/refractory SCLC is expected to start in the second half of this year, with regulatory bids officially to be made in the U.S. and Europe during 2009.
Pharmion also has subcutaneously administered Vidaza (azacytabine) for myelodysplastic syndromes, holding its ground against competitors such as Dacogen (decitabine) from SuperGen Inc. and Revlimid (lenalidomide) from Celgene Corp. In the U.S., Canada, and Mexico, MGI Pharma Inc. owns rights to Dacogen.
Pharmion sells its thalidomide product for multiple myeloma and leprosy (licensed from Celgene and Penn T Ltd. for all countries outside of North America, Japan, and mainland China), and markets Innohep (tinzaparin), a low-molecular-weight heparin approved in the U.S. for deep-vein thrombosis, as well as Refludan (lepirudin), an antithrombin agent approved in the U.S., Europe and other countries for heparin-induced thrombocytopenia.
In late February, Pharmion with partners GPC Biotech AG and Spectrum Pharmaceuticals Inc. reported the final progression-free survival results from the Phase III SPARC registration trial of the platinum-based agent satraplatin, which compared the drug when added to prednisone to placebo plus prednisone in 950 patients with hormone-refractory prostate cancer. Satraplatin significantly reduced the risk of disease progression, according to results offered at the American Society of Clinical Oncology Prostate Cancer Symposium. A new drug application was filed earlier the same month.
Amrubicin, though, takes the spotlight for now. Digging deeper, Lazard's survey found that about 17 percent of lung cancer patients treated by responders are diagnosed with SCLC (in line with figures kept by the national Surveillance Epidemiology and End Results database) and the rest for NSCLC. About 68 percent of patients show up with extensive disease, and the remainder with localized tumors.
For front-line SCLC, a cisplatin/carboplatin combination is the preferred choice. Forty-five percent of physicians polled used carboplatin with etoposide, followed by 41 percent choosing cisplatin with etoposide, as front-line treatments for SCLC patients with extensive disease.
Doctors said that about 60 percent of their more-ill SCLC patients are treated front-line, compared to 40 percent treated in a relapsed/refractory setting, where GSK's Hycamtin rules. Eight-five percent of responders there chose Hycamtin - the only approved drug for the indication. Hycamtin has yielded an overall response rate of 24 percent in relapsed/refractory cases, with median survival of around 6 months. Combining cyclophosphamide, doxorubicin, and vincristine garnered similar survival data, but an overall response rate of only 18 percent.
The questions that Lazard asked doctors were based on an assumption that amrubicin, in the Phase II trials still under way, can get a 60 percent to 80 percent overall response when combined with cisplatin front-line, and a 40 percent to 50 percent rate in second-line. The physicians' answers led to a bright forecast that could become even better if amrubicin can take away some front-line carboplatin users.
If there's a potential cloud on Pharmion's horizon - one acknowledged by Lazard - it's picoplatin, the new-generation platinum therapy from Poniard Pharmaceuticals Inc., set to enter a Phase III trial for second-line SCLC. In January, Poniard reached a special protocol assessment agreement with the FDA, and will conduct a single Phase III trial, labeled Study of Picoplatin Efficacy After Relapse (SPEAR).
The firm expects to enroll about 400 patients, randomized in a 2:1 ratio to compare intravenous picoplatin plus best supportive care to best supportive care alone. The study, which should take about 20 months to complete enrollment and follow-up, will include patients who are refractory to treatment with the likes of cisplatin or carboplatin or who have progressed within six months of completing those treatments.
Poniard, formerly NeoRx Corp., acquired picoplatin from AnorMed Inc. in 2004. Julie Rathbun, spokesperson for Poniard, told BioWorld Financial Watch that the drug has been tested in more than 600 patients, including work done by AstraZeneca plc, and the Phase III trial is slated to start shortly, with enrollment taking about a year. Picoplatin is also undergoing Phase I/II tests in colorectal tumors and hormone refractory prostate cancer.