FDA Rejects Caterpillar Vaccine

Flu Shot Made From Caterpillars Fails Safety Vote

By Tom Randall

Nov. 19 (Bloomberg) — Protein Sciences Corp. failed to prove its experimental flu vaccine is safe enough to be approved and more study is needed, a U.S. advisory panel said.

The shot, called FluBlok, is produced in less than two months by inserting flu genes into an insect virus and growing it in caterpillar ovary cells. Members of the advisory panel to the U.S. Food and Drug Administration voted 6-to-5 that the company hadn’t proven the vaccine safe, saying clinical trials weren’t large enough to support mass production. Nine of the 11 panelists said the shot was as effective as licensed vaccines in adults ages 18 to 49.

Closely held Protein Sciences, based in Meriden, Connecticut, and backed by $147 million in U.S. contracts, is seeking to become the country’s first supplier to break from the 50-year-old technique of growing the vaccine in chicken eggs. The egg-based process has been blamed for delays in this year’s pandemic swine flu vaccine, and U.S. health officials have pledged to increase production times.

“The reason we’re struggling so much is the safety database isn’t very large,” said Pamela McInnes, director of the Division of Extramural Research at the National Institutes of Health and one of the panelists. “The company has clearly done some nice work, and there’s been a lot of progress made. There’s not a signal in my mind that I’m very worried, but we are missing information.”

Patient Hospitalized

There were several examples of face swelling reported in clinical trials, and one person was hospitalized for a condition called pleuropericarditis, characterized by swelling around the heart and lungs. While the hospitalized patient had reported fever, shortness of breath and chest pain a week before he was vaccinated, the shot couldn’t be ruled out as a contributor to his illness, panelists said.

Staff documents released by the FDA ahead of today’s panel hearing said the vaccine was found to be as safe and effective as other flu shots in four human trials covering 3,231 adults ages 18 and older. Panelists today said that because the vaccine wasn’t significantly more effective than competitors, the company needed to prove safety in larger trials in order to justify approval.

While the FDA usually follows its panels’ recommendations, the agency isn’t required to do so.

The new swine flu strain identified in April has infected 22 million Americans and killed about 3,900, according to the Atlanta-based CDC. More people with flu symptoms sought treatment from doctors in October and November than at the February peak of a normal flu season, according to data on the CDC Web site. The U.S. flu season runs from November to March.

Vaccine Delays

Vaccine to combat the swine flu, known as H1N1, began arriving in October, and about 50 million doses are available for shipment, health officials said yesterday. That’s less than half what officials projected in July for the end of October.

Novavax Inc., which has enrolled 1,000 recipients in clinical trials of a competing technology, rebounded in Nasdaq Stock Market composite trading on the panel’s decision. The shares fell 4 cents, or 1 percent, to $3.77 at 4 p.m., after declining as much as 6.6 percent during the meeting. The Rockville, Maryland-based company makes a vaccine from virus- like particles, structures that mimic the flu without causing infection.

Early Bets

Novartis AG, based in Basel, Switzerland, London-based GlaxoSmithKline Plc and Baxter International Inc. based in Deerfield, Illinois, made early bets on a method of growing the live vaccine in cultured animal cells. Novartis, which sells vaccine using the cell-based technique in Europe, received U.S. contracts for $487 million to build a production plant in North Carolina.

The animal-cell process, which relies on growing the live virus in cells, may prove less dependable than Protein Sciences’ technique, said William Schaffner, chairman of the department of preventive medicine at Vanderbilt University in Nashville, Tennessee, before today’s meeting.

“Variability is gone, the egg allergy is gone, purity increases so it can be much more refined — that’s exciting to us,” Schaffner, who is a consultant for the U.S. Centers for Disease Control and Prevention’s advisory committee on vaccines, said in a telephone interview. “We are at the beginning of some major changes in influenza vaccine technology.”

Not Necessarily Faster

Animal cell-based technology isn’t necessarily faster than egg-based, Philip Hosbach, vice president of immunization policy and government relations for the vaccine unit of Paris-based Sanofi-Aventis SA, said yesterday at a congressional oversight hearing in Washington. Vas Narasimhan, president of Novartis’s U.S. vaccine unit, said the cell-based method may save six to eight weeks of production time.

“The big companies are going with mammalian cells, which really doesn’t make any sense,” said Daniel Adams, chief executive officer of Protein Sciences, in a telephone interview before the panel met. “You’re substituting mammalian cells for eggs, but you still have to use a live virus. You still have to wait for a seed strain from the CDC.

“People for a long time thought you could deal with a pandemic using eggs,” Adams said. “My gut reaction is that change comes slowly, but I certainly expect our technology to be a major player in the flu.”

Adams didn’t immediately return a phone call for comment after the panel vote.

Cell-Based Shots

Novartis’s cell-based vaccines for seasonal flu and swine flu, approved for use in Europe, show the safety and effectiveness of the production method, company spokesman Eric Althoff said in an e-mail. The drugmaker’s technique produced the first batch of swine flu vaccine, he said.

“Existing technologies are here now; they’re tried and true,” Donna Cary, a spokeswoman for Sanofi, said today in a telephone interview. She said Sanofi is evaluating new vaccine technologies including cell-based production and a so-called universal vaccine that would cover all strains and wouldn’t need to be re-administered each year.

A Glaxo representative couldn’t be reached.

Most seasonal flu vaccines are made by taking versions of the three most-commonly circulating influenza strains and growing the virus in millions of chicken eggs. The virus is then removed from the eggs and damaged so it can’t cause infections. Some strains grow faster than others, and a poorly performing seed virus such as the pandemic swine flu, can delay production, which typically take 5 to 6 months.

Caterpillar Virus

Protein Sciences extracts genes from the dead flu virus and inserts it in a virus that feeds on a tropical caterpillar known as an armyworm. The virus is then exposed to ovary cells harvested from a single caterpillar and reproduced in large quantities. Ovary cells are used because they remain stable as they are cultured in a laboratory.

The caterpillar virus feeds on the ovary cells in vessels similar to those used to ferment beer, and there isn’t the variability of trying to grow a live flu virus that isn’t well adapted for chicken eggs, said Adams of Protein Sciences. The consistency of the caterpillar virus growth cuts down on the manufacturing time.

The end result is a vaccine made of protein and salt water, he said. Because the vaccine is pure, preservatives such as thimerosal aren’t necessary.

Protein Sciences fought off an involuntary bankruptcy suit by creditor Emergent BioSolutions Inc. in September. In addition to its government contracts, the company is funded by private investors including Wyeth, which was acquired by New York-based Pfizer Inc. for $68 billion in October.