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0 5 - 0 7 - 2 0 0 5 Hollis-Eden files IND for Neumune in the US
Source: Datamonitor Newswire
Hollis-Eden Pharmaceuticals has filed an Investigational New Drug application with the FDA to begin phase I clinical trials in human volunteers with Neumune, a possible treatment of acute radiation syndrome, in the US.
A similar phase I clinical trial for Neumune is currently ongoing in the Netherlands. Acute Radiation Syndrome (ARS) is a potentially lethal condition caused by high-dose radiation exposure that might result from a nuclear or radiological terrorist attack or from an accident at a nuclear facility.
Hollis-Eden is developing Neumune under an FDA rule (the Animal Efficacy Rule) designed for medical countermeasures to weapons of mass destruction. According to this rule, for indications in which it would be unethical to conduct efficacy studies in humans (as is the case with radiation injury), marketing approval may be granted based on the demonstration of efficacy in relevant animal species and successful completion of phase I safety trials in humans.
Hollis-Eden has already conducted and reported on dose-ranging radiation studies in over 200 non-human primates. In animals receiving moderate doses of radiation, Neumune has demonstrated a reduction in the incidence of neutropenia (loss of white blood cells), thrombocytopenia (loss of platelets) and anemia (loss of red blood cells) compared to animals not receiving the compound. In animals receiving high doses of radiation, Neumune demonstrated a reduction in both febrile neutropenia and severe thrombocytopenia, as well as a survival benefit as compared to animals not receiving Neumune.
Pivotal studies in non-human primates, designed to demonstrate efficacy in support of a planned New Drug Application (NDA) filing, are expected to begin in the second half of 2005.
Under the phase I clinical trial program, in addition to analyzing safety, initial studies are being conducted to determine the concentration of Neumune that can be achieved in human blood. This pharmacokinetic (PK) information can then be used in selecting the final dose for the pivotal efficacy study in non-human primates, as well as a larger human clinical trial to demonstrate safety.
Under the Animal Efficacy Rule, matching the drug levels in humans with that which produces efficacy in the appropriate animal species is a requirement for approval. By comparing the concentration of Neumune that can be achieved in humans to that which has already been established in non-human primates, the company expects to be able to match the dose most likely to achieve efficacy in the pivotal studies with a dose that is achievable and tolerable in humans.
The studies to be conducted in the US are designed to complement the clinical program that has already commenced in the Netherlands.
Selling safety
San Diego company lobbying government to buy huge stockpiles of its experimental anti-radiation drug
By Penni Crabtree With any luck, Hollis-Eden Pharmaceuticals' science will prove to be as effective as its politics. For about 18 months, the San Diego drug developer has been slugging away on Capitol Hill to raise the profile of its experimental anti-radiation drug and to push for passage of Project BioShield, a $5.6 billion government plan to purchase and stockpile vaccines and antidotes to counter a biological or nuclear attack. To achieve its goals, Hollis-Eden executives have spent about two weeks of every month in Washington, D.C., meeting with legislators, regulators, congressional committee staffers and the military, according to the company. Last year, Hollis-Eden executives and directors gave $18,000 in campaign contributions to President Bush and policy-makers influential in the BioShield debate. The company also paid more than $225,000 last year to two lobbying firms, according to federal records. That investment helped land about $2.5 million in Department of Defense and National Institutes of Health funding to be used specifically to develop Hollis-Eden's drug, Neumune, at a military research institute. It's a lot of politicking for a company that still hasn't conducted a final study in radiation-dosed primates to demonstrate if, and how well, the drug might work in humans. Yet the behind-the-scenes maneuvering indicates just how high the stakes are for tiny Hollis-Eden. The money-losing company, which has never entered into a significant corporate research collaboration or mounted a major clinical trial for any of its experimental steroid-based drugs, wants the government to commit to buying hundreds of millions of dollars worth of Neumune. Such a contract would make Hollis-Eden profitable almost overnight. Hollis-Eden founder and chief executive Richard Hollis acknowledges that the past year and a half has been a kind of "Mr. Hollis Goes to Washington" odyssey. Except Hollis isn't exactly the dewy-eyed, Jimmy Stewart type. "If anything has ever been a no-brainer, I'd like to think this (Neumune) is it," Hollis said. "But when you are dealing with governments and bureaucracies and Capitol Hill, nothing is a no-brainer. Everything has to be earned." Last month, Hollis-Eden and other companies working on potential BioShield products achieved a major goal when the Senate passed BioShield legislation. The Senate must now reconcile its bill with one that the House passed earlier, and then Bush is expected to sign BioShield into law. That means the next round of political maneuvering has already begun. Hollis-Eden and other drug companies are jockeying to assure a place for their experimental products on the anticipated A-list of drugs the government will commit to buy first, according to one Washington lobbyist. "Everyone is trying to figure out where and how to touch the elephant," said Frank Rapoport, a lobbyist who represented a La Jolla biotech, smallpox drug developer Chimerix, in Washington. "There isn't enough money to buy everyone's product. The big uncertainty is whether companies like Chimerix or Hollis-Eden can convince the government to put them at the top of the list." There, too, Hollis-Eden may have a political ace up its sleeve. Hollis said his company is working with Rep. Darrell Issa, a Vista Republican, on a bill designed to specifically support the stockpiling of radiological countermeasures. "If it doesn't happen right away, through BioShield or anything else, he (Issa) is looking at this as an absolute necessity," said Hollis, who remained vague about the wording of the proposed bill. Issa's office said the congressman is reviewing BioShield legislation to see if there are needs that the bill does not address. Hollis-Eden's political and scientific quest to get a potential BioShield drug approved and purchased by the federal government could serve as a road map for biotechs with similar ambitions. For Hollis-Eden, the road to Washington began at Ground Zero. Just days after the terrorist attack on the World Trade Center in September 2001, Hollis said he received a telephone call from Navy Adm. James Zimble, a top military health official. Fears of future acts of terrorism, including the possibility of a nuclear or "dirty" bomb that could spew harmful radioactive materials, had suddenly made Hollis-Eden's compound a top priority for government researchers, Zimble said. The Armed Forces Radiobiology Research Institute (AFRRI) in Bethesda, Md., had been experimenting since about 1997 with the steroid 5-androstenediol, the chemical name for Neumune. Hollis-Eden owns rights to the steroid as a treatment for radiation exposure, as well as other medical uses. Zimble told Hollis that the steroid showed promising results in early studies and the military wanted to push it forward as a possible treatment for radiation sickness. The problem? AFRRI didn't have the money or the mandate to get into the drug-development business. As it turned out, AFRRI and Hollis-Eden proved to be a perfect match – both were underfunded scientific waifs in need of a success. Hollis-Eden was founded by Hollis, a former marketing executive for Genentech who was hunting for a promising class of compounds around which to build a company. He hit on the naturally occurring steroid hormone dehydroepiandrosterone, or DHEA, and with patent rights acquired from another company, Hollis-Eden went public in 1996. Over the years, Hollis-Eden licensed other DHEA-related compounds, including in 2000 the compound that later was named Neumune. The company studied the steroids as potential treatments for everything from AIDS to malaria, and while some promising data were generated, little commercial progress was made. AFRRI was also adrift in a scientific and political backwater. Prominent during the Cold War, the research institute founded in 1961 had faded into a minor Department of Defense player. In the mid-1990s, the department issued a directive aimed at closing AFRRI and shifting its core research elsewhere; meanwhile, the institute's budget had dwindled to about $10 million. Until recently, AFRRI scientist Mark Whitnall, who heads the Neumune project, said he had a core supply and test animal budget of only $14,200 to devote to studying Neumune. It soon became clear to Hollis-Eden that if it was going to have a meaningful shot at developing Neumune – and getting the government to buy it – the profiles of both the company and AFRRI had to be raised. In February 2002, Hollis-Eden signed a joint research agreement with AFRRI to develop Neumune, and then set about making both known on Capitol Hill. In December 2003, Hollis-Eden hired the Washington lobbying firm Bracewell & Patterson. On the night in January 2003 when President Bush proposed Project BioShield in his State of the Union address, Hollis and other company executives were planning strategy at Bracewell's offices. Those strategies included getting more federal funding for AFRRI and the Neumune project, and increasing awareness in Congress and the Pentagon about AFRRI as an expert on radiological countermeasures – including Neumune. Ultimately, Hollis-Eden lobbyists helped persuade the Defense Department to allocate an additional $2.5 million in the fiscal 2004 budget to AFRRI – $2 million of it earmarked for Neumune research. Another $500,000 was allocated by the NIH for the same purpose. Meanwhile, Hollis-Eden and its lobbyists also worked to secure a government contract for the purchase of Neumune, with or without the passage of BioShield. In the process, the company navigated a maze of departments and agencies, each with its own committees and staffs, including the Department of Defense, the Department of Health and Human Services, the Department of Homeland Security and the White House Office of Science and Technology Policy. Also visited, sometimes repeatedly, were some 20 to 30 lawmakers in the House and Senate. In April 2003, Hollis donated $2,500 to a political action committee of Bill Frist, the Senate majority leader who largely controls if and when bills come up for a vote. And a month later, Hollis-Eden hired another lobbying firm, Larson Dodd Stewart & Myrick, whose principal, Dave Larson, was a former health policy adviser to Frist. Hollis said employing lobbyists "comes with the territory" when dealing with the government as a potential customer. "Navigating through Washington, unless you have someone on the ground who knows the departments, it's impossible," Hollis said. "It was cost-effective marketing, and the way I look at marketing is being able to give the decision- maker the information." In July 2003, the House passed legislation to put BioShield in place. But the bill bogged down in the Senate as lawmakers wrangled over a variety of issues, including concerns that the law would permit noncompetitive bidding on some contracts. Days, weeks and months dragged on without BioShield budging. "We kept lobbying to find out what was happening, and quite honestly, we weren't getting a lot of straight answers – so we just kept working on the science," Hollis said. BioShield took a back seat for a number of reasons, according to Washington observers. Congress was more than a little distracted by the Iraq war, launched in March 2003. And there was the contentious debate over the Medicare reform bill and its prescription drug benefit, which was widely viewed as a giveaway to the pharmaceutical drug industry. The timing for another bill that would hand large purchasing orders to drug companies wasn't deemed right, said Hollis and some lobbyists. Yet Hollis-Eden continued to do what it could to advance research into Neumune, and to keep it in the minds of politicians. On Aug. 14, 2003, Bush arrived in San Diego for a fund-raiser at the San Diego Convention Center. Among the attendees was Hollis, who, along with seven other Hollis-Eden executives and directors, donated a collective $16,000 to Bush. Hollis is pragmatic about the campaign contributions to Bush and Frist. "We wanted to see BioShield passed," Hollis said. "I don't care what politician it is. I'm for anybody who is for our nation's security." In the case of Bush, the campaign contribution earned Hollis a few private minutes with the president to talk about Neumune and BioShield. Hollis-Eden also worked to keep the company on the minds of investors, doing interviews with the media and appearing in national and international publications. On Sept. 26, 2003, Hollis joined former New York Mayor Rudy Giuliani, who had started his own consulting firm with a specialty in security and homeland defense, to ring the opening bell of the Nasdaq market. Meanwhile, lobbyists working for biotechs with potential BioShield products, and others with an interest in the bill, stepped up their efforts, including "planting" stories with various newspapers in an effort to break the Senate logjam. For instance, in the Jan. 26, 2004, edition of The Washington Times, lawyer Robert Housman wrote a lengthy commentary about the threat of a nuclear attack and the need to pass BioShield. The article highlighted the work of Hollis-Eden while chiding the slow-moving Senate for its failure to pass BioShield. "If approved, this drug could save hundreds of thousands of lives in a nuclear attack on a major city," Housman wrote. "Had the federal government moved expeditiously, this nuclear countermeasure would already be fully tested and stockpiled. However, the drug has been unnecessarily delayed for more than two years." The article identified Housman as co-author of the Homeland Security Law Handbook. It didn't mention that Housman had previously been a paid Hollis-Eden lobbyist while working for Bracewell & Patterson. In the end, more than 2 years after Sept. 11 and 17 months after Bush proposed Project BioShield, the Senate finally passed BioShield. Housman, now a Hollis-Eden lobbyist at the Washington firm of Fleishman-Hillard, said that other biotechs can draw a lesson from Hollis-Eden's experience on Capitol Hill. But it isn't necessarily a comforting one. "If you are looking at yourself as the next Hollis-Eden, you can take away a couple of things," Housman said. "Don't think this will be an easy process, and don't think just because you have the next great thing you will be greeted with a chorus of cheers and contracts." 2 4 - 0 9 - 2 0 0 5 Nuke attack drug contracts up for grabs Feds to tap drug makers for stockpiles against radiation poisoning
September 23, 2005 NEW YORK (CNN/Money) - As Americans brace themselves against Hurricane Rita, the second huge hurricane in one month, the government is preparing to spend some serious money on another potential threat: nuclear attack. As part of Project Bioshield, the Department of Health and Human Services has been allocated $5.6 billion to build up the Strategic National Stockpile with drugs, vaccines and therapies to prepare for the threat of terrorist attacks. About $1 billion of this budget has already been spent on contracts, mostly for anthrax vaccine, but $4.6 billion still remains to prepare against other threats, including radiation poisoning, according to HHS spokesman Mark Wolfson. On Sept. 30, the HHS plans to publish a draft of a Request for Proposal, seeking input from companies working on therapies for radiation sickness resulting from a nuclear attack. Such an attack would most likely come from a "dirty bomb," where a conventional explosion, disguised in a car or a suitcase, would scatter radioactive material in a major city. The government is seeking drugs that treat Acute Radiation Syndrome, which causes bone marrow damage, causing the body to succumb to infection and death. Drug makers Hollis-Eden Pharmaceuticals, Amgen and Akorn, Inc. are all potential candidates for the government's RFP, according to Wolfson and analysts. The HHS wouldn't say how much it is planning to spend on radiation therapies, and the size of the Bioshield contracts have varied widely so far. VaxGen Inc. was awarded the largest bid of $877 million for anthrax vaccine, while Bioport Corp. received a $122 million contract for anthrax vaccine and Fleming & Company was awarded a $6 million contract for potassium iodide to treat radiation sickness in children. Wolfson said there could be multiple recipients in the next Bioshield contract, or it might just fall to one bidder. "We're not limited to awarding to just a single company," said Wolfson. Hollis-Eden Acute Radiation Syndrome breaks down white blood cells and platelets in the bone marrow, eroding the body's ability to fight the bacteria, often leading to death within weeks of radioactive contamination. Hollis-Eden is developing Neumune, an injectable therapy that would rebuild white blood cells and platelets in victims of radiation poisoning. The company has completed testing in 200 rhesus monkeys for treatment of radiation contamination, which showed an average mortality rate of 12 percent with Neumune, compared to 32 percent without, according to chief executive officer Richard Hollis. Neumune has not yet been submitted to the Food and Drug Administration, but it would not need FDA approval to fill a government contract for Bioshield. Neumune could be supplied to first responders and private citizens in the form of kits, and could sidestep expensive or unavailable hospital treatments, said Robert Marsella, senior vice president for Hollis-Eden. "The hope is that we could reduce the mortality rate in a nuclear scenario where we could help tens of thousands of victims," said Marsella. Joseph Pantginis, analyst for Adams Harkness, Inc., believes that an HHS contract to buy Neumune could total $700 million over four years, which would be a significant source of revenue for a company with no products on the market. Hollis-Eden staffers would not project how big they expected a Bioshield contract to be. "It comes to how many millions of Americans does the government want to protect in a nuclear scenario," said Hollis, the CEO. "I certainly think a radiation threat is more significant than an anthrax threat, that's for sure." Akorn Akorn's anti-radiation drugs Ca-DTPA and Zn-DTPA work by purging the body of radioactive elements. The drugs were granted fast-track orphan drug status by the Food and Drug Administration in 2004, said David Moskowitz, analyst for Friedman, Billings, Ramsey. Also, Akorn is the sole bidder on a Bioshield contract that, according to HHS spokesman Wolfson, is separate from the RFP draft that will be announced Sept. 30. Moskowitz projects that the sole-bid contract could total $10 million to $30 million if the government is seeking enough doses to protect a single region of the U.S., or up to $100 million if the HHS is looking for wider distribution. Akron would pull in additional sales if it is included in the second RFP. Amgen Amgen, the largest biotech in the world with $10 billion in 2004 sales, has two drugs that are used to cleanse the body of radioactive elements: Neulasta and Neupogen. These drugs, which combined bring in nearly $3 billion in company sales, are used to reduce infection in chemotherapy patients and could be used to rebuild white blood cells in victims of radiation sickness. However, Pantginis, the Adams Harkness analyst, said Amgen is handicapped in competing for the RFP bid because its products don't rebuild platelets. "Neupogen/Neulasta only works on white blood cells and therefore only addresses 50 percent of the government's request for properties of the therapeutic," wrote Pantginis in a Sept. 19 report. Given the negative publicity showing the government's mishandling of Hurricane Katrina, Moskowitz said the feds appear to have their act together with Bioshield. "This type of activity shows that the government is stepping up to get its major cities prepared" for nuclear attack, said Moskowitz. Akorn and Amgen were not immediately available for comment. The analysts interviewed for this story do not own stock in the companies mentioned here. |
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[Definitie:] "An ergogenic aid is any substance or phenomenon that enhances performance."
(Wilmore and Costill) 
