Washington Editor

The FDA has given Agennix Inc. the go-ahead to proceed with a pivotal Phase III trial testing talactoferrin alfa, a recombinant form of human lactoferrin - a glycoprotein found in breast milk - in patients with non-small-cell lung cancer (NSCLC).

The study's design was approved under an FDA special protocol assessment (SPA), a binding agreement that the design and planned analyses of the trial will adequately support a biologics license application. That SPA is "an important milestone," Agennix CEO Rick Barsky told BioWorld Today.

The Phase III multinational, randomized, double-blind, placebo-controlled trial is examining talactoferrin, a dendritic cell activator, in combination with chemotherapy in patients previously untreated for NSCLC. About 1,100 patients will be enrolled at 200 to 250 global sites, Barsky said, and they will be randomized to receive up to six cycles of the chemotherapy agents carboplatin and paclitaxel plus either twice-daily dosages of liquid talactoferrin or placebo.

Following six cycles of chemotherapy, or discontinuation prior to six cycles for reasons other than progression, patients will receive either talactoferrin or placebo as maintenance therapy until disease progression.

The primary endpoints of the study are progression-free survival for accelerated approval and overall survival for regular approval. Secondary endpoints include reduction in adverse events, confirmed response rate, duration of response and safety.

In a separate parallel trial of 720 patients, Agennix is investigating talactoferrin as a monotherapy in those who have failed two or more chemotherapies, Barsky said. In that trial, he noted, about two-thirds of the participants will be randomized to receive talactoferrin, while the remaining third will receive placebo.

Both Phase III NSCLC trials will be conducted simultaneously at many of the same global sites, Barsky said.

The timeline for completing the trials is within two years of the start dates, he said, noting that there will be a three-month start-up period followed by a one-year enrollment period. The firm expects to have data about eight months after completion of enrollment, Barsky added.

While Agennix is ready to start the Phase III trials from a regulatory standpoint, he said, the company first must complete a financing round. To date, the firm has raised more than $100 million in private equity.

In a Phase II trial, talactoferrin in combination with chemotherapy as first-line treatment in patients with advanced NSCLC met its primary endpoint of improvement in response rate, Barsky noted. And in a second NSCLC Phase II study, talactoferrin demonstrated activity as monotherapy in patients with refractory disease and met its prospectively defined primary endpoint of improvement in overall survival.

In addition, Barsky noted, in both Phase II trials, talactoferrin showed statistically significant reductions in total adverse events.

"The toxicity profile is really tremendous," he said. "Not only in the Phase IIs did we see no material increase in toxicity when patients took talactoferrin, but we actually saw a reduction in some of the chemotherapy toxicities in the first-line trial where we combined it with chemotherapy. It means that this can combine well with a variety of different agents."

Talactoferrin, discovered in 1988 by Bert O'Malley, chair of molecular and cellular biology at Baylor College of Medicine in Houston, has been tested in more than 600 patients, some of whom have continued receiving the compound for more than two years, Barsky said.

Agennix, of Houston, licensed talactoferrin from Baylor in 1993 and manufacturers the drug through fermentation in Aspergillus niger, a filamentous fungus that is structurally identical in all material respects to native human lactoferrin, which plays an important role in helping to establish the immune system, including the gut-associated lymphoid tissue in infants. A. niger differs from lactoferrin only in its glycosylation.

Agennix also is investigating talactoferrin in renal and other cancer types, Barsky said, adding that the company plans to soon release final results of a Phase II study of talactoferrin in patients with renal carcinoma.

Agennix recently received a $3 million grant from the National Institutes of Health to study the compound as a treatment for sepsis, Barsky said.

In addition, he said, the firm is exploring a topical formulation of talactoferrin as a therapy for diabetic foot ulcers.