Bioscope ‘08

by  Dr. Barbara Price

Advances in defense vaccines

          Early in March 2008, Pharmathene made two business investments to secure their place as a top provider for CB medical defense products in the US. They bought Avecia's biodefense vaccines business, a UK company, and extended their agreement with GTC Biotherapeutics Inc., to process Protexia®, a pegylated form of recombinant human butyrylcholinesterase (rBChE). rBChE is a potent organophosphate (OP) scavenger being developed for use as a prophylactic and therapeutic against acute OP nerve agent toxicity. Protexia® is produced in the milk of transgenic goats.

          How many dollars did the US give to Bioport and Dynport, the companies that evolved from Michigan Biologic Products Institute, the former manufacturer of the US vaccine? That is an obscure amount. In 1998, just after taking over the MBP, Bioport received a $29 million contract from DOD. HHS awarded a $122.7 million contract to BioPort Corporation (currently Emergent BioSolutions) in May, 2005 for 5 million doses of the AVA vaccine. 2006, HHS purchased an additional 5 million doses of AVA at a cost of $120 million. In April 2007, HHS planned to acquire 10.4 million doses of a licensed anthrax vaccine, with an option to purchase up to an additional 8.35 million doses. (This is 28 million doses for about $722 million or just over $25 per dose.)

          Avecia's biodefense vaccine line includes a second-generation recombinant Protective Antigen (rPA) anthrax vaccine, a recombinant dual antigen plague vaccine, and a third generation rPA anthrax vaccine program. Both the anthrax and plague vaccines are recombinant vaccines originally developed by Dstl (Defence Science & Technology Laboratory) in the UK. The anthrax vaccine is a recombinant PA, adsorbed on Alhydrogel, and, Avecia, together with Dstl, used Avecia's fermentation expertise and manufacturing capabilities to increase the production up from laboratory scale. In Sept 2003, Avecia, received a $71.3 million contract from NIAID for 3 million doses of a new recombinant anthrax vaccine.

          Interestingly, researchers at the USAMRIID (Fort Detrick, MD) also developed the "next-generation" anthrax vaccine, "a highly-purified genetically-engineered protein called recombinant PA plus Alhydrogel". And Canadian researchers "developed a monoclonal antibody (mAb) specific for a recombinant PA that is capable of neutralizing the in vitro cell-killing activity of lethal toxin." Other research groups have also published research papers on mAb for recombinant forms of PA and taken out patents on their mAbs.

          In 2006, Pharmathene received orphan drug status from the FDA, for Valortim, a mAb against PA they were developing with Medorax, a NJ company. The orphan drug status enables Pharmathene (and Medorax) to be "eligible for special tax credits and grant funding opportunities, reduced filing fees and a seven-year window of market exclusivity if the drug should earn regulatory approval." The US's Orphan Drug Act was created to encourage companies to develop new therapies for rare conditions, particularly those affecting fewer than 200,000 people in the US.

          Will the new alliance with Avecia mean that Pharmathene will continue to develop Valortim and a drug using the UK based mAb? Does the Orphan Drug Act also cover this new rPA mAb, or is that limited to Valortim, the venture with Medorax?

          Emergent Biosolutions, EB, the heir to Michigan Biologics Products Institute (MBPI) and Bioport and related to Dynport, also announced this month that it bought a group of anthrax mAb from AVANIR Pharmaceuticals. AVANIR's lead product candidate, AVP-21D9, a fully human monoclonal antibody. EB has the only currently FDA-approved product, BioThrax® the old anthrax vaccine that was originally produced by MBPI and Bioport with poor quality control and subsidized by DOD when the low bid could not deliver. According to its website, EB is developing a polyclonal antibody (or immune globulins) intravenous treatment for those exposed to anthrax. NIAID provided funding of up to $13.4 million for a combination of initiatives related to the polyclonal antibody, including non-clinical efficacy studies and a human safety and pharmacokinetics study.

          AVANIR has also received funding from NIH/NIAID, including an initial $100,000 under the SBIR program in 2003, $750,000 under a phase II of the SBIR in 2004, and $2 million in 2006 to establish a cGMP manufacturing process; this was extended in May 2007 for another up to $2 million to include government reimbursement of certain expenses in the effort to meet cGMP. Remember meeting cGMP was one of MBPI and Bioport's problems; lack of cleanliness, lack of quality control and documentation (lab controls, stability of solutions, SOPs, etc.) meant the recall of many batches of anthrax vaccine. EB now has funding to make sure it can meet pharmaceutical manufacturing standards. How many times has the government paid companies to meet cGMP?

          There are some other companies involved, too. In 2006 HHS made two more awards under Project Bioshield, a contract for 20,000 treatment courses of ABthrax, an mAb from Human Genome Sciences (Rockville MD) for $165 million and a contract for 10,000 treatment courses of Anthrax Immune Globulin (AIG), the polyclonal antibody vaccine, from Cangene Corporation (Manitoba Canada) for $144 million.

          AVANIR and VaxGen had a cross-license and research collaboration agreement for the development and manufacture of pre-clinical supplies of AVANIR's monoclonal antibody candidate for prevention and treatment of anthrax infection. In 2004, VaxGen had received more than $100 million in government funding to develop its anthrax vaccine candidate made from rPA, the vaccine candidate based on USAMRIID's patented discovery. VaxGenÕs vaccine candidate was composed of an alum adjuvant and a purified protein, rPA. In September 2003, VaxGen received $80.3 million from NIAID to make 3 million doses of its new anthrax vaccine. In Dec 2006, HHS canceled its $877.5 million contract with VaxGen Inc. for a new anthrax vaccine, after problems with the vaccine's stability caused the company to miss a deadline for starting a clinical trial. The contract, awarded in 2004, called for VaxGen to produce 75 million doses of a new anthrax vaccine for the US civilian stockpile, or enough to immunize 25 million people (hardly an orphan drug), and was the first and largest contract awarded under Project Bioshield. During this same period, NIH/NIAID continued to fund work in the UK by Avecia, now bought by Pharmathene. On March 29, 2008 VaxGen decided to call off its potential merger with Raven Technologies and may liquidate the company.

Editors Note: There are times when this editor feels like coming down with both feet on the nonsense that permeates this area. We spend hundreds and hundreds of millions of dollars for millions of doses of a vaccine for anthrax, a non-contagious disease, i.e., which does not spread from person to person. If we were worried about an anthrax being very widely disseminated, we had better worry about an anthrax that has been genetically modified. Consider the source capabilities. If that were the case, these hundreds of millions of dollars spent on developing tons of anthrax vaccine would be truly wasted because these vaccines would be worthless. Even if a terrorist had a truck or crop duster or several of each - how much area could be covered with a garden variety of anthrax? Isn't it time to use common sense rather than billions of cents to start solving our true bio problems. Let's put these funds to work on real pandemic problems and problems of BW agents that pose more of a threat than fear. No wonder the ethical vaccine manufacturers would not touch this area with the proverbial 10 foot pole.

For the Professional in Government and Industry with an interest in Nuclear, Biological and Chemical Defense, Disarmament and Verification; Emergency and Disaster Medical Planning; Industrial Health and Safety; and Environmental Protection