Last week's potential $455 million deal that Idera Pharmaceuticals Inc. signed with Merck & Co. Inc. was more about vaccines than anything else, but the agreement also turned investor eyes to an important oncology indication: renal cell carcinoma (RCC), the most common form of kidney cancer, for which Idera has the Phase II Toll-like receptor 9 agonist IMO-2055.
Merck's pact with Idera gives the pharma giant exclusive worldwide rights to agonists for TLR7, TLR8 and TLR9 for use as adjuvants in vaccines for cancer, infectious disease and Alzheimer's.
Sudhir Agrawal, CEO and chief scientific officer of Idera, told BioWorld Financial Watch the firm had been talking with Merck "not for too long" before the adjuvant deal came to pass. "Applications of TLR agonists have started to show some clinical data from other parties," he noted.
Idera gets $30 million up front from Merck, which includes the purchase of $10 million in Idera stock at $5.50 per share, and as much as $425 million in milestone payments - $165 million if Merck makes successful vaccines, and $260 million for follow-on indications in cancer.
The deal also includes a two-year research collaboration, allowing Idera (formerly Hybridon Inc.), which now has 30 scientists in the discovery area, to double its capacity. Such work has given Idera not only the TLR9 agonist IMO-2055 for RCC (for which Phase II data are due in the middle of next year) but also IMO-2125 for hepatitis C virus, a TLR9 agonist of a different structure, Agrawal said, due to enter the clinic shortly.
Of all kidney tumors, about 85 percent consist of RCC, and about 38,000 new cases are expected in the U.S. this year, with more than 12,000 deaths. RCC hits men twice as often as women, and risk factors include smoking, extra weight and chronic dialysis. The disease is very difficult to treat, once it has spread.
Along with the kidney cancer trial, Idera has IMO-2055 in a dose-escalating Phase I/II trial at the Lombardi Comprehensive Cancer Center at Georgetown University Medical Center. The Phase I portion is designed to evaluate IMO-2055 in combination with gemcitabine and carboplatin in solid tumors, and the Phase II aspect will test the same combo as front-line therapy in non-small-cell lung cancer patients, after an optimal dosage regimen is chosen in the first part of the study.
Idera scientists have published work in Cancer Clinical Research, showing how its TLR9 agonist seems to impair the signaling pathway of epidermal growth factor receptor, thus boosting the anticancer activity of Erbitux (cetuximab), the compound for colorectal cancer from ImClone Systems Inc. and Bristol-Myers Squibb Co.
Combo therapy might give Idera's drug an important edge as it competes against Sutent (sunitinib), from Pfizer Inc., and Nexavar (sorafenib), from Onyx Pharmaceuticals Inc. and Bayer AG.
Nexavar, which won approval for kidney cancer a year ago, fizzled in a Phase III trial against advanced melanoma this month, failing to improve progression-free survival when compared with placebo in melanoma patients. Each arm included treatment with carboplatin and paclitaxel, but the company said its "enthusiasm for Nexavar is not diminished," in the words of Julie Wood, Onyx's vice president of investor relations and corporate communications.
The FDA cleared Sutent in January. Both drugs target the VEGF pathway and both are undergoing trials in tumor types beyond kidney cancer. Still, wrote analyst Ren Benjamin in a research report, Idera "represents a compelling turnaround story for the long-term, risk-oriented investor" - albeit not, perhaps, as compelling overall as Genentech Inc., which also reported kidney cancer news with its blockbuster Avastin (bevacizumab).
First given the go-ahead for marketing in 2004 as a colorectal cancer therapy, Avastin has gained drug compendia listings for breast and lung cancers (in May 2006 and September 2005, respectively), which means insurance companies and Medicare will reimburse for them. The drug is widely used off label, but Genentech needs formal FDA clearance to rev sales more powerfully in those indications.
With partner F. Hoffmann-La Roche Ltd., Genentech last week reported an interim analysis of the Phase III study known as AVOREN, in which metastatic kidney cancer patients given interferon-alpha plus Avastin showed significantly improved progression-free survival vs. those on interferon-alpha plus placebo, the primary endpoint. On the secondary endpoint - overall survival - Avastin patients seemed to improve, but there wasn't enough information yet for a final analysis.
The study randomized 649 patients with first-line disease to get interferon-alpha plus 10mg/kg of Avastin or placebo every two weeks. Avastin showed a safety profile consistent with other trials (adverse events included bleeding, hypertension, and proteinurea), with significant adverse events including gastrointestinal perforation.
Data from a Phase III trial being run parallel with AVOREN, called CALGB 90206, are due at the American Society of Clinical Oncology meeting, to be held in June in Chicago. Avastin earlier proved its mettle in a Phase II trial testing the drug as a second-line therapy, with a time to progression of 4.8 months vs. 2.5 months for placebo. Avastin seems particularly interesting to researchers because kidney cancer often stems from a mutation of the Von Hippel Lindau tumor suppressor gene, which leads to overproduction of VEGF.
Another potential RCC therapy to make headlines recently is Exelixis Inc.'s XL999, for which the firm last month suspended Phase II trials due to adverse cardiovascular events, and the delay was expected to last from two weeks to three months. Of the 131 patients enrolled in the program, 16 experienced such events. The multi-kinase inhibitor (one of eight compounds Exelixis has in the clinic) also is undergoing testing as a single agent for colon cancer, ovarian cancer, NSCLC, acute myelogenous leukemia and multiple myeloma.
Days after the suspension, Exelixis reported at the EORTC-NCI-AACR meeting in Prague, Czech Republic, updated Phase I data with XL999 that showed preliminary evidence of antitumor activity when given intravenously once per week or every two weeks. Of the 45 patients enrolled as of Oct. 1, three had partial responses and 10 others have had stable disease for three to 25.5-plus months. Identified as the dose-limiting toxicities were cardiac failure and elevated hepatic transaminases.