Editor

"NSCLC" might sound like a sports league to some, but the acronym has a much more dire meaning to physicians and their patients, who battle a disease yet to meet its match in the laboratory despite the best efforts of biotechnology firms.

Non-small-cell lung cancer takes in several cancer types - most prominently, squamous cell and adenocarcinoma - that make up about 85 percent of the tumors in lung cancer, which afflicts more than 3 million people.

In the U.S., well more than 360,000 people are living with the disease, with more than 172,000 new cases expected this year, when 163,000 are expected to die from it, according to the Surveillance Epidemiology and End Results (SEER) program of the National Cancer Institute.

Very grim. What's more, SEER finds the five-year survival rate for lung-cancer patients is about 14 percent, and has stayed at that level for decades. Between 60 percent and 70 percent of patients (or 85,000 to 100,000 per year) will get first-line treatment, and half will move on to second-line therapy.

The National Comprehensive Cancer Network reports that the most common first chemotherapies for NSCLC are cisplatin or carboplatin combined with one from a handful of drugs: paclitaxel, docetaxel, gemcitabine, vinorelbine, irinotecan, etoposide, vinblastine. Cisplatin, sold as Platinol-AQ, is from Bristol-Myers Squibb Co., as are Paraplatin (carboplatin) and Taxol (paclitaxel).

Second-string players are pemetrexed, docetaxel and gefitinib. Sanofi-Aventis Group sells docetaxel, the taxane derivative that blocks cell mitosis, as Taxotere.

Gemcitabine, from Eli Lilly and Co. (which also offers pemetrexed as Alimta), is viewed as a heavy hitter in first-line therapy, but others coming up include Telik Inc.'s Telcyta, which in July reported positive interim data from two Phase II studies. In one trial, researchers saw objective tumor responses in 15 patients, for a 58 percent objective response rate. In the other, objective partial responses showed up in eight patients for a 32 percent objective response rate.

Telcyta is the first in a new class of cancer cell-activated chemotherapeutics designed to exploit the overexpression of glutathione S-transferase P1-1, an enzyme too much present in many cancer cells. High levels are associated with a poor prognosis and resistance to certain chemo approaches.

Approved second-line weapons, along with Taxotere and Alimta, include the much-ballyhooed Tarceva (erlotinib), from Genentech Inc. and OSI Pharmaceuticals Inc.

In all, 16 drugs have been cleared by the FDA for use against lung cancer. And every one of them, viewed from the standpoint of survival rates, might be deemed losers, notes a new report by Chrystyna Bedrij and Theodore Harlan from Griffin Securities. Overall response rates range between 8.8 percent and 9.1 percent, with median survival between 6.7 months and 8.3 months, and median time-to-progression settling out at between 3.1 months and 3.5 months.

Alimta and Taxotere get similar efficacy as single agents in second-line treatment, but Alimta boasts the better toxicity profile and is positioned as a "mainstay" in that space. "This, from our viewpoint, would displace the more toxic Taxotere to a third-line agent," the Griffin report said.

What's on the horizon? Pegged as "the one we are most excited about," Griffin said, is talotextrin, from Hana Biosciences Inc., a new-generation anti-folate therapy in development as a single agent in second-line NSCLC therapy, as well as ongoing and planned trials in solid tumors, leukemia and cervical cancer. In NSCLC, a Phase I/II trial started this year. In May, Hana also started a Phase I/II study with the drug as a single agent in adults with relapsed or refractory acute lymphoblastic leukemia.

Lilly's Alimta also is an anti-folate, but talotrexin holds the most promise of any in the class, according to Griffin's report.

"Unlike classical anti-folate, anti-neoplastic agents such as [methotrexate] and Alimta that require polyglutamation to be highly cytotoxic, talotrexin is highly efficacious without polyglutamation," thereby getting around the resistance problem, the report said, concluding that talotrexin "has the potential to displace Alimta as well as other treatments and dominate the market in the NSCLC single-agent, second-line setting."

In early August, Hana was awarded a $159,000 Small Business Innovation Research grant by the National Institutes of Health to expand preclinical studies of talotrexin in combination with other agents for cancers.

Griffin's Bedrij and Harlan also like talabostat, the lead compound from Point Therapeutics Inc., an oral small molecule in a number of Phase II trials. During the second quarter of this year, at the American Society of Clinical Oncology meeting, Point reported positive data from a 41-patient Phase II study in metastatic NSCLC, when combined with docetaxel. Of the first 36 evaluable patients, five showed a significant tumor response, with two gaining a complete response - and adding talabostat to docetaxel did not significantly affect safety.

A Phase III study with talabostat is expected in the second half of this year. Meanwhile, in June, Point started a 60-patient Phase II trial with the drug when combined with gemcitabine against metastatic pancreatic cancer. The primary endpoint is six-month survival.

But it's Hana's compound, as well as the company itself, that Bedrij was most enthused about. Last week, the company - which Bedrij, who specializes in finding small firms with particular potential, has pegged as a winner - updated investors on the status of its pipeline, including talotrexin, and its long-term goals.

Hana said its oral spray, Zensana (ondansetron), could reach the market in 2007, and there was encouraging talk about talotrexin.

In that drug, Bedrij told BioWorld Financial Watch, "I think they have something. It's going to be a blockbuster."

No Comments