LONDON - The academic partner of Peptide Therapeutics Group plc received approval from the FDA to mount the first challenge clinical trial of Peptide's single-dose, oral typhoid vaccine, a move the company said will cut development time by two years.
“It is very hard to get this type of approval, and we are very fortunate to get it,“ Nick Higgins, director of licensing, told BioWorld International. “It will allow us to do a cheaper trial which is quicker and more relevant. It will cut two years off the time taken to get a product license.“
In the trial, to be carried out by Mike Levine, of the University of Maryland at Baltimore, 100 volunteers will be given unattenuated typhoid in escalating doses to assess the dose at which 75 percent of them get the disease. A second group will be given Peptide's oral vaccine, which is attenuated by the removal of three genes, and then challenged with the same dose of typhoid that infected 75 percent of the first group.
While Levine intends to test a number of typhoid vaccines in this way, Peptide's will be the first. Any license granted as a result of this trial would be for travelers' typhoid. For the vaccine to be licensed for use in countries where typhoid is endemic, it would be necessary to conduct controlled trials in those areas. Peptide already has a Phase II trial for safety and immunogenicity of the oral typhoid vaccine under way.
Higgins said that, to date, 40 out of 80 subjects have received the vaccine. They all have shown an immune response, and there have been no adverse effects.
Peptide, of Cambridge, U.K., licensed the vaccine from London-based Medeva plc, which has first rights to an option to commercialize it. In January 1997 the two set up an alliance for R&D and marketing of non-injectable vaccines. Under the deal Peptide acquired technology and patents for £1 million, and is paying Medeva £1 million over two years toward the cost of R&D carried out at Medeva's Vaccine Research Unit at Imperial College, in London.
The collaboration covers two other vaccines: oral ETEC (enterotoxigenic Escherichia coli) for prevention of travelers' diarrhea, due to enter Phase I trials in the final quarter of 1998; and an intranasal flu vaccine, currently in Phase I trials.
Peptide also announced it has ditched one of its key compounds, a therapeutic for rheumatoid arthritis (RA), after it failed to show efficacy in a Phase II pilot study.
Peptide's approach to RA, pioneered by the company's founder, Denis Stanworth, was to break down the complex formed between immunoglobulin A and alpha 1-antitrypsin in the synovial fluid of RA patients, a previously unexplored target.
However, the tetrapeptide designed to do this did not bring about any significant reduction in levels of the complex in any of the patients.
“This was disappointing, since allergy and rheumatoid arthritis were the two indications around which Stanworth founded the company,“ Higgins said. “But the data clearly said drop it. The Phase II was quick and cheap to do, and biotechnology companies shouldn't be afraid of dropping compounds.“
Peptide has a second rheumatoid arthritis treatment in development, based on a peptide derived from a heat shock protein that has the ability to modulate inflammatory processes. This currently is being evaluated ex vivo, and a decision will be made whether to proceed with a Phase I trial in the second half of 1998.
Peptide's R&D Spending Doubles
Peptide made these updates on its product development when it released results for the year ended December 1997 showing losses up to £6.45 million from £4.5 million in 1996.
Expenditure on R&D almost doubled, to £9.7 million from £5 million in 1996. Turnover rose to £2.8 million in 1997 from £0.2 million in 1996, mainly due to the £2.4 million in license fees received from SmithKline Beecham plc, of London, for Peptide's broad-spectrum allergy vaccine.
Peptide said it ended 1997 with £20.8 million in cash, an increase of £0.2 million over 1996 and sufficient to fund the company for the next two and a half years.
“We are happy with these results,“ Higgins said. “R&D costs are up mainly because we have more people; we now have 90 staff vs. 70 or so the year before. We also are happy to have more money at the year end than we did at the beginning.“
The increase in cash came from new equity issues of £3 million to Medeva and £3.6 million to SmithKline.
Higgins said the deal with SmithKline for Peptide's lead product, an allergy vaccine designed to prevent all allergic responses, is proceeding well with the technology transferred from Peptide to SmithKline.
SmithKline is conducting Phase II feasibility trials in allergic asthma, hay fever, anaphylaxis and food allergy, with initial results expected in 1999.
As part of the collaboration, Peptide is working on backup allergy vaccines. One of these, a tolerizing peptide to prevent hay fever caused by rye grass pollen, entered Phase II studies in March 1998. SmithKline has an option to license this product and will decide whether to take up the option when the Phase II data is available in the final quarter of 1998. *