A collaboration between Acambis PLC and the Flanders Interuniversity Institute for Biotechnology aims to develop a “universal” influenza vaccine, which would not have to be altered each year.

    Every year the FDA Vaccines and Related Biological Products Advisory Committee meets to decide what strains of the influenza virus should be included in the vaccine for the following autumn, Center for Biologics Evaluation spokesman Paul Richards said. The committee contains representatives from, the Centers for Disease Control, the World Health Organization and the Department of Defense.

    There are two main strains of influenza, A and B, according to CDC. Both are continually mutating, so it is necessary to have a new vaccine every flu season, Richards said. Production takes about six months.

    This creates a problem, according to Paul Glezen of the Baylor College of Medicine, because new variants often do not surface until after the vaccine is set.

    If a “universal” vaccine were developed, it would eliminate this difficulty.

Richards noted that the FDA has historically supported research into a vaccine that could protect people for more than one year. If the science can support a “universal” solution, it could “cure, mitigate or prevent” influenza, according to a statement Dr. Jesse Goodman, CBER director. 

    If a person is vaccinated, they are exposed to a harmless version of virus, including the particular surface proteins specific to that strain, Glezen explained. The person will develop antibodies bind to these surface proteins and prevent them from binding to their targets and allowing the infection to take hold.

    Influenza A is the most frequently pandemic strain, said Richard Weltzin, senior director of viral immunology at Acambis. This is because the virus mutates most rapidly, according to CDC. Most influenza A viruses target one of two receptor proteins, Glezen said. Hemigglutinin attaches to cells in the lungs and neuraminidase helps the infection progress.

    But Acambis is working on a virus that targets a protein called M2e, Weltzin said. This is a channel that allows charged molecules to flow into the interior of the virus and make it acidic. 

    Its role is not completely understood, according to Weltzin. But it does not elicit much of an immune response from the body. As a result there are not antibodies that attach to it and it does not mutate very often. 

    So Acambis is trying to enhance the immune response to M2e by attaching a particulate carrier protein to a virus-like particle that will enhance the reaction to M2e. The drug amantadine, which is sometimes used to treat influenza A, works on the M2e receptor, Weltzin said. 

    Acambis acquired the influenza A vaccine technology from Apovia, which licensed it from the Flanders Interuniversity Institute for Biotechnology.

It is working with the university to discover a target protein for influenza B that is similar to M2e, Weltzin said. 

Articles

This vaccine specialist is attempting to create a product that will protect people from influenza A for every future flu season without re-formulation. They are thinking about how to fight influenza B, too.

Acambis Working to Create a Universal Flu Vaccine

Just four days after an FDA advisory committee put an end to further trials of migraine treatment MT100, manufacturers Pozen Inc. submitted a New Drug Application for another migraine medication, Trexima (Sumatriptan Succinate and Naproxen Sodium).

    The Peripheral and Central Nervous System Drugs Advisory Committee voted unanimously that MT100 did not provide enough benefit, especially since it is only indicated for migraine patients without nausea. The risks of a neurological disorder associated with one of its components, metoclopramide hydrochloride, were said to be too high.

    Metoclopramide, which acts against dopamine receptors, is associated with a disease called tardive dyskinesia, according to a memo to the committee written by Dr. Eric Bastings, the team leader of the Division of Neuropharmacological Drug Products. TD causes repetitive uncontrollable movement, especially in the mouth, such as smacking lips and sticking out of the tongue, Bastings said.

    Peter Young, president of specialist investment banking firm Young & Partners, described the Trexima NDA as a substitute for the failed approval. Pozen promised a quick NDA submission when it announced its decision to halt further research on MT100. The submission was earlier than the end-of-September date many expected, according to Fran Barsky, the company’s director of investor relations.

    The strategy appears to have worked. The two announcements prompted only small movements in the company’s stock prices. They fell 5.1 percent to a price of $7.97 Aug. 4, the day of the announcement. Prices rebounded to $8.29 the next day but dropped 31 cents after the Trexima NDA was filed.

    Like MT100, Trexima contains naproxen. But instead of metoclopramide, it uses sumatriptan succinate, the generic name for GlaxoSmithKlein’s Imitrex. Trexima’s future may be boosted as a result of this partnership with GSK, which is the leader in migraine treatment, Barsky said.

    “We are very happy to be collaborating with them on this,” she stated.

    According to GSK spokeswoman Robin Gaitens, Pozen is responsible for Trexima’s development, clinical trials and regulatory filings. GSK will commercialize all formulations of the drug.

    Analysts may still have some doubts about Trexima’s ability to succeed. In April, after Pozen announced the Phase II trial results for Trexima, Piper Jaffray analyst Deborah Knobelman said she was “cautious” about the drug’s likelihood of approval. But just before the NDA was submitted, Knobelman said that the approval prospects were “marginally higher.”

Migraine specialist abandons one problematic drug and maintains its position by filing an NDA the following week.

Pozen Files NDA Days After Advisory Committee Rejection

Two new genome-sequencing techniques allow the genetic material of an organism to be read on a smaller scale than previously, allowing it to be done more quickly and cheaply. 

    Both Harvard Medical School and Connecticut-based 454 Life Sciences Corp. developed sequencing techniques that move toward the National Human Genome Research Institute’s goal of human genome sequencing for $100,000 in the short term. NHGRI hopes the process will eventually be accomplished for $1,000. A human genome currently costs $10 million, according to the organization.

    “The NIH-NHGRI genome sequencing technology project is barely a year old and these two methods suddenly show that ‘incremental’ improvements are not the only game in town,” Harvard Medical School spokeswoman Judith Montminy said via email.

    Glenn Schulman, spokesman for 454 Life Sciences, explained that the ability to routinely sequence the human genome would allow researchers to understand how hundreds of genes function. This would increase scientists’ understanding of complex diseases.

    In a statement encouraging the $1,000 genome goal, Francis Collins, NHGRI director, said, “not only will these technologies substantially reduce the cost of sequencing a genome, but they will provide a quantum leap in the scope and scale of research aimed at uncovering the genomic contributions to common diseases, such as cancer, heart disease and diabetes.”

    Inexpensive sequencing would show the “true value of pharmacogenomics,” Shulman predicted. This would allow researchers to understand how people respond differently to different drugs.

    He also indicated that the technique could be used to help understand the HIV virus and predict how it resists certain drugs. 

The 454 technique begins by attaching single-stranded DNA fragments to silica-coated beads, with each bead containing only one fragment, Schulman explained. These are then amplified so that each bead contains multiple, identical fragments. 

    The beads are placed on a special fiber-optic slide, according to Schulman. The slide is then inserted into 454’s sequencing machine. A solution containing one type of nucleotide, for example just adenine (A), is washed across the plate allowing it to pair with thymine (T) bases in the single stranded fragments on the bead. When the pairing occurs, it causes light to be released by activating luciferase, an enzyme involved in giving fireflies their characteristic glow.

    The 454 machine is able to tell the position and number of the base pairings by reading the light reactions, Schulman said. The slide is then washed with a second type of nucleotide and the process is repeated until the entire molecule is known.

    According to Schulman, this process can be used to re-sequence already mapped genomes or to assemble the sequence of an unknown genome, a process called de novo sequencing.

    The Harvard process is similar, according to Montminy. It also uses DNA fragments attached to beads. But the fragment is read by attaching nucleotides that are each marked by a different colored dye. The molecules are placed in a gel and a special microscope, common to many labs, is used to read the pattern of colors and know the sequence of nucleotides. This is compared to a known genome sequence.

    This is one of the main differences between the two techniques. According to Montminy, the Harvard technique can only be used to detect differences between the DNA of an individual and an already mapped genome. It can detect mutations but cannot sequence an unknown genome. 

    Montminy said, however, that the Harvard technique is more accurate, 99.7 percent versus 96 percent. It is also less expensive, she said. The machine used to read the sequence in the 454 technique costs about $500,000. The microscope used by Harvard costs $140,000.

    But she did point out that 454’s technique is faster. Schulman added that the 454 method is also able to read a longer fragment of DNA.

Only a year after the National Human Genome Research Institute called for improving sequencing technology, two new methods were announced in the same week. What will the goal of a $1000 human genome mean for medicine and disease research?

Pharmaceutical Executive-08-16-2005

Acambis Working to Create a Universal Flu Vaccine

Pozen Files NDA Days After Advisory Committee Rejection

Two New Techniques Make Genome Sequencing Faster and Cheaper