By Jim Shrine

Special To BioWorld Today

Megabios Corp. and Targeted Genetics Corp. have each released data from early studies on their approaches to delivering the CFTR gene to cystic fibrosis (CF) patients.

Megabios said that in a Phase I/II study, its gene-based product GR213487B proved safe and produced no signs of inflammation when delivered in an aerosol plasmid formulation. Targeted Genetics reported no adverse events from a Phase II study of tgAAV-CF, a product using an adeno-associated virus to deliver the CFTR gene.

Results from the studies were presented Thursday at the North American Cystic Fibrosis Conference in Montreal. Both companies are trying to deliver a normal copy of the cystic fibrosis transmembrane regulator (CFTR) gene to CF patients, whose loss of gene function causes production and buildup of thick mucus in the lungs and sinuses. That prevents clearing of bacteria and leads to infections and failed lung function.

Megabios, of Burlingame, Calif., and London-based development partner Glaxo Wellcome plc tested GR213487B by delivering it to the nasal passages of 11 adult CF patients. Researchers reported vector-specific plasmid was seen up to five days after treatment in some patients and there was a possible trend toward CFTR correction, with a mediated chloride defect in the treated side of the noses. Levels of vector-specific mRNA, however, were not seen.

"The results we got in Phase I were exactly as expected," Bennet Weintraub, vice president, finance, and CFO for Megabios, told BioWorld Today. "We weren't looking for efficacy so there is not specific data on" the chloride defect.

Glaxo is analyzing results and will decide how to move forward, Weintraub said. One possibility is moving to a Phase I or I/II study in which the product is delivered to the lung, he said.

Megabios has received $5.3 million in research funding from Glaxo since the collaboration started in 1994. The company can receive additional milestone payments — including one for the start of Phase III studies — and royalties on sales. Glaxo is responsible for clinical trials, marketing and sales.

Targeted Genetics Also Pursuing Aerosol Delivery

Aerosol delivery of the CFTR gene is the direction in which Targeted Genetics is moving. The Seattle company, which is developing the product itself, also is looking at delivery to the lung as a next step.

Targeted Genetics' Phase II study with 23 patients was designed to assess safety and the effect of tgAAV-CF in preventing recurrence of sinusitis. Each patient was treated with the drug in one sinus and placebo in the other.

While sinusitis recurred in more than 60 percent of patients, the analysis has not been done to determine whether it was in the treated or untreated sinuses. Those results are expected by the end of the year.

"This is a preliminary look at what we've seen," H. Stewart Parker, president and CEO of Targeted Genetics, told BioWorld Today. "Meanwhile, we are gearing up for the aerosol trial that will happen by the end of the year. We hope the sinus study will give us some preliminary glimpse at what will happen in the lung."

An aerosol version of the same tgAAV-CF product is the one the company would expect to take forward. Aerosol allows widespread delivery to the lungs and also is easier on patients.

Targeted Genetics brought in consultants to help develop the aerosol formulation, and is in discussions with potential partners, Parker said.

Patients in the Phase II study were monitored for changes in serological markers, including detection of circulating vector and antibodies that would inhibit the viral vector. No serious adverse events were reported in follow-up periods of more than three months.

The study followed a Phase I trial that demonstrated tgAAV-CF provided efficient gene transfer and gene persistence up to 70 days in the maxillary sinus. The company said efficacy of the product in preventing infections in the maxillary sinus might be a good model for lung disease, since both result from thick mucus stemming from loss of CFTR function.

"We're excited about AAV, not only for delivery of CFTR but as a delivery platform for a lot of genes that should be expressed for long periods of time, with no side effects," Parker said. *