AVI Biopharma doled out an interesting little morsel of news on its muscular dystrophy drug right before Christmas that showed encouraging results in three boys. This year, the Bothell, WA-based biotech company is eagerly awaiting more meaningful follow-up data that could show it is on track with what could be the first treatment to fix the underlying molecular abnormality in boys with Duchenne Muscular Dystrophy.

I got the update on AVI’s game plan for 2010 when I met with a few senior executives, including chief financial officer David Boyle and chief medical officer Steve Shrewsbury, a couple of weeks ago in San Francisco. We talked a little bit about the company’s RNA-based treatments for hemorrhagic viruses like Ebola, as well as a new government-funded flu program. But there’s no doubt the main event this year will be what happens with the company’s treatment for Duchenne Muscular Dystrophy.

AVI Biopharma (NASDAQ: AVII) wants to be the first company to make a drug that silences a specific strand of RNA, and enables the body to produce a protein called dystrophin. This is a protein that’s essential for enabling muscles to rebuild themselves, and is lacking in boys with a birth defect known as Duchenne Muscular Dystrophy. This is a crippling disorder that affects about one out of every 3,500 boys born worldwide.

“Duchenne Muscular Dystrophy is certainly our lead program, and we think it has significant value,” Boyle says.

The AVI approach made some medical news in The Lancet last year, when the company showed that its RNA-based treatment was able to restore production of dystrophin proteins when injected directly into a foot muscle. That prompted the next step, in which AVI developed a version of the drug that could be delivered intravenously, and circulate throughout the body, where it could presumably have a much broader impact on muscles.

The first peek at data from this trial of the intravenous version came out in December. This initial slice of data was from the first nine patients who were enrolled in the four lowest dose groups. Researchers found that in three patients who got doses on the high end of that range, the molecular abnormalities dissipated. One boy was able to produce five-fold higher amounts of dystrophin. “These results suggest that we are on the right path,” said Francesco Muntoni, the trial’s lead investigator at University College London, in a statement.

I wanted to know about the next steps to watch for in the clinical development of this drug, called AVI-4658. It turns out that AVI has two major data releases planned for 2010, and both will be closely watched by parents, researchers, and shareholders.

The first release will be before the end of June. The trial, for those unfamiliar … Next Page »

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Bothell, WA-based AVI Biopharma (NASDAQ: AVII) is trying to develop the first treatment to correct an underlying molecular abnormality in boys with Duchenne Muscular Dystrophy, and after taking an early peek at a small clinical trial, the drug appears to be doing what it’s supposed to do in at least one patient.

The preliminary results were from an initial phase trial from the first 9 out of 18 boys who completed dosing at a single site in the U.K., with once-weekly intravenous infusions of the treatment, AVI-4658, over a period of 12 weeks. The trial initially enrolled patients to receive extremely low doses of the drug, and when it appeared safe, enrolled more patients in higher dose groups. AVI Biopharma and its academic collaborators didn’t see evidence of an effect at the lowest doses, but they did among three boys who got mid-range doses of 2 and 4 milligrams per kilogram, which showed the drug corrected the molecular abnormality it is designed to fix. One of the boys was able to produce five-fold higher amounts of a protein called dystrophin, a key structural component of muscle that is lacking in patients with Duchenne Muscular Dystrophy, based on a biopsy of bicep muscle.

AVI doesn’t have data in hand that connects the dots to show that the molecular changes induced by the drug will actually reverse the disability associated with muscular dystrophy. Still, “these results suggest that we are on the right path towards developing a drug that could play a role in the treatment of Duchenne Muscular Dystrophy,” said Francesco Muntoni, Professor of Pediatric Neurology and Head of the Dubowitz Neuromuscular Centre at the University College London, and the trial’s lead investigator.

“We weren’t really expecting to see dystrophin expressed, based on the animal models, until we got to higher doses of 4 and 10 milligrams per kilogram,” says AVI chief medical officer Steve Shrewsbury. “It’s a nice way for us to round out the year and start the new year.”

Biotech companies haven’t traditionally shown much interest in muscular dystrophy, although that’s changing as researchers gather understanding of the genetic underpinnings of the disease. The AVI treatment is part of an emerging class of compounds known as antisense oligonucleotides.

What’s special about the AVI treatment is that it’s designed … Next Page »

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The day I stopped by to visit Seattle’s newest biotech company, the building was chilly on one side and hot on the other. An assistant wasn’t sure at first where the light switch was in the conference room. Nobody answered right away when I called from the security phone outside.

“Hopefully the next time you come out here, we’ll figure out how the building works,” joked Les Hudson, the CEO of AVI Biopharma (NASDAQ: AVII).

AVI has reason to be a little disorganized since it just moved its headquarters from Portland, OR to Bothell, WA last month, as part of its strategy to grow into a more serious player in the field of RNA-based drugs that can treat underlying causes of disease in ways that traditional therapies can’t. The company (which is keeping some labs in Corvallis, OR) has gone through a metamorphosis this year, seeing its stock shoot up from 45 cents in the past year to $1.61 at the last close, on some progress with its first-in-class experimental treatments for Duchenne Muscular Dystrophy and Ebola and Marburg viruses. AVI, which entered the year with $11.4 million in cash in the bank, has seized on that momentum to raise another $50 million from Wall Street this year.

This is a pretty remarkable shift for a company founded in 1980, that has burned through $271 million of capital, and never in its history developed an FDA approved drug. The transition has happened under Hudson, 62, an immunologist who previously led Nabi Biopharmaceuticals, and DOV Pharmaceutical, after spending longer stretches of his career at Pharmacia and GlaxoSmithKline.

AVI moved in to space on Monte Villa Parkway in Bothell that used to be occupied by MDRNA (NASDAQ: MRNA). About 14 people at AVI had moved to the Bothell office on Sept. 17, the day I met with Hudson and AVI’s chief medical officer, Steve Shrewsbury. They have now posted 11 job openings to help boost the company’s capabilities in a number of areas, notably regulatory affairs.

Hudson was due to personally scope out a new apartment in Bellevue, a town which he says he likes because it’s close to the office and has “bright lights at night.” Hudson and Shrewsbury are still getting the lay of the land, and figuring out how to network to take advantage … Next Page »

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One of the Seattle biotechs that’s been flying low on the radar this year popped back up on the scene with news of an important partnership.

—Seattle-based Trubion Pharmaceuticals had its best day of the year last Friday, when it said it secured a partnership with Redwood City, CA-based Facet Biotech (NASDAQ: FACT) to co-develop a drug for chronic lymphocytic leukemia. The deal provides Trubion with $20 million in upfront cash, plus $10 million in equity investment from Facet. Shares in Trubion (NASDAQ: TRBN) shot up more than 40 percent on news of the deal.

—Bad news hit one of the stars of the Seattle medical device cluster this week as Redmond, WA-based Archus Orthopedics filed paperwork to dissolve the company. The company raised more than $60 million from a prominent group of venture investors since 2001, before it ran out of cash this year. Archus showed great promise, at least according to one patient who got its spinal implant in a clinical trial in 2006.

—Merck (NYSE: MRK) looked like it delivered a body blow to Seattle biotech last October when it said it was shutting down its Rosetta Inpharmatics division, sending 300 workers into an uncertain job market. It didn’t turn out to be as damaging to the region as first feared, as more than 110 Rosetta alumni will keep doing what they’re good at in local jobs at Covance, Microsoft, and Sage Bionetworks.

—Biotech companies haven’t had much progress to brag about toward a real treatment of the underlying cause of Duchenne Muscular Dystrophy, the crippling genetic disease in young boys, but Bothell, WA-based AVI Biopharma has a chance to be a trailblazer, University of Washington neuroscientist Jeff Chamberlain told me during an in-depth interview.

—UW’s entrepreneurial bioengineering professor, Buddy Ratner, organized a conference on campus last week that attracted one of the top life sciences entrepreneurs of the past decade, Tufts University chemistry professor David Walt. I caught up with Walt, the co-founder of San Diego-based Illumina (NASDAQ: ILMN), for an exclusive interview on where he thinks genomics is heading, and his next big idea for a company.

—The Seattle-based Infectious Disease Research Institute licensed some technology from an Israel-based company for “microneedles” that might be a less painful way to inject its experimental vaccines, and might have the added benefit of better stimulating powerful immune system cells just under the surface of the skin.

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Jeff Chamberlain first heard about muscular dystrophy as a kid watching the annual Jerry Lewis telethon on Labor Day weekend. That TV program has been raising awareness for 43 years about this genetic disorder that breaks down muscles, eventually crippling and killing young boys and men, usually by their 20s.

The disease really captured Chamberlain’s curiosity about 25 years ago, when in graduate school he started studying the basics of how muscles form. He’s now a professor of neurology at the University of Washington, and a leading researcher attempting to develop the first drugs that can go beyond treating the symptoms of muscular dystrophy, and actually affect the underlying genetic disorder. He’s also a scientific advisor to CureDuchenne, an advocacy group for patients with the most common form of the disease, Duchenne Muscular Dystrophy.

Biotech companies haven’t shown much interest in muscular dystrophy, although that’s changing as researchers gather understanding of the genetic underpinnings of the disease. One leading candidate in this new class of treatment is from Bothell, WA-based AVI Biopharma (NASDAQ: AVII). The AVI treatment is part of an emerging class of compounds known as antisense oligonucleotides. It’s designed to silence a specific stretch of RNA that can enable the body to produce a protein called dystrophin. The protein is essential for muscles to be able to rebuild themselves, and is lacking in patients with muscular dystrophy. The drug recently earned notice in The Lancet when it showed an ability to restore some production of dystrophin proteins in an early-stage clinical trial—although it didn’t fully restore the dystrophin.

If AVI can show in subsequent trials that its drug is safe, and can be delivered throughout the body, it would be a big step forward even if it’s modestly effective, Chamberlain says. About one in every 3,500 boys born worldwide have Duchenne Muscular Dystrophy.

Jeff Chamberlain

Chamberlain spoke with me in depth about how the standard of care for Duchenne Muscular Dystrophy has evolved, which drugs show promise in development, which companies are leading the way, and what patients can realistically expect from treatments of the future. Here is an edited account of the interview:

Xconomy: How did you first get interested in Duchenne Muscular Dystrophy?

Jeff Chamberlain: In graduate school, I was more interested in developmental biology, in terms of how does a human body form from a single fertilized egg. I ended up in a laboratory that was studying muscle development, as in how does muscle form. I wasn’t focused on diseases, but became interested in muscle tissue, and as soon as you start working on muscle, you hear about the muscular dystrophies because it’s a common genetic disorder.

I grew up watching the Jerry Lewis telethon, every Labor Day, which the Muscular Dystrophy Association puts on. A lot of the funding for basic muscle research was coming through the Muscular Dystrophy Association. So you couldn’t help but want to learn more.

The focus of my project was the importance of genes in regulating muscle growth. So when I graduated and went off to do postdoctoral training, I was recruited by a lab that wanted to study the genes involved in muscular dystrophy.

X: What year was this?

JC: About 1985. This was before any of the genes were known that cause muscular dystrophy.

X: Was the thinking then that this was a single gene disorder?

JC: Yes, that was known even then. Because all the muscular dystrophies … Next Page »

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AVI Biopharma, the Portland, OR-based developer of RNA-based therapies, said today it has been awarded part of a $2.5 million contract from the U.S. Department of Defense to develop a drug for Duchenne Muscular Dystrophy. The contract, awarded to researchers at the Children’s National Medical Center in Washington D.C., will support animal studies to develop AVI-4658. AVI (NASDAQ: AVII) will serve as a subcontractor, the company said.

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Biogen Idec has turned down the requests of the family and high-profile friends of a dying patient at the Mayo Clinic to provide an emergency dose of Tysabri to try to combat the man’s cancer—an unapproved use of the drug. It’s a vivid example of the ethically treacherous zone that companies must traverse when patients request access to their drugs before they are approved as safe and effective by the FDA.

The case of Frederick Baron hit the blogosphere in a open letter to Biogen CEO James Mullen posted this morning by Baron’s son, Andrew. The letter grabbed instant attention (including from TechCrunch’s Michael Arrington, who wrote a scathing post about Biogen’s refusal), in part because Andrew Baron, CEO of RocketBoom, noted that celebrities including Lance Armstrong, former President Bill Clinton, U.S. Senators Ted Kennedy and John Kerry, among others, all personally called on Biogen to clear the way for their friend to get an emergency dose of Tysabri. Frederick Baron, 61, a famous trial attorney and prominent Democratic fund-raiser, has multiple myeloma, a deadly cancer of the bone marrow; Tysabri is only approved by the FDA for the treatment of multiple sclerosis and Crohn’s disease.

Normally, with a marketed drug like Tysabri, physicians like those at the Mayo Clinic in Rochester, MN, are free to prescribe it for any disease, or any dose, however they see fit, under what is known as “off-label” use. The situation is more complicated with Tysabri, because it is currently available only under a strict prescribing and monitoring program called Touch; the program was instituted when Tysabri was brought back to the market in July 2006 after having been withdrawn in 2005 because of its link to a rare and often fatal brain infection called PML. Tysabri is now taken by an estimated 32,000 patients worldwide with multiple sclerosis and Crohn’s disease.

Frederick Baron’s physician hit upon the idea of treating him with Tysabri because samples of his cancer cells turned out to carry a molecular marker that Tysabri, an antibody drug, is designed to seek out and block, according to Andrew Baron’s letter. Biogen has done some animal tests that suggest Tysabri might be an effective treatment for multiple myeloma, and in fact, it began treating the first patient in a clinical trial of Tysabri against the condition last month, says company spokeswoman Naomi Aoki. Frederick Baron’s physician is an investigator on this study and well-familiar with its rules, but Baron isn’t eligible to participate in the trial because he is too sick, Aoki says.

In his letter, Andrew Baron wrote that FDA commissioner Andrew von Eschenbach “has granted special approval” for his father to receive Tysabri, which essentially puts the ball in Biogen’s court. Under FDA rules, the company has discretion to give out the drug for such unapproved uses—what is known as “emergency use” or “compassionate use”—but it chose not to, Aoki says. If something went wrong in an uncontrolled setting, it might lead to further restrictions on the drug’s use among existing patients with MS and Crohn’s disease, she says.

“We concluded when we re-introduced Tysabri that we cannot make it available for uses other than the FDA-approved use, or for an FDA-approved clinical trial,” Aoki says.

Still, I asked if this was a difficult decision, given the life and death nature of the matter. Andrew Baron’s letter says his father may have only a day or two left to live. “Of course, it’s a difficult decision for us. Our thoughts go out to the family. We don’t take this lightly, but we feel we have a responsibility to protect patients already on this drug who are benefiting from this drug,” Aoki says.

When asked if legal liability is part of the company’s concern, Aoki referred back to her statement about protecting the interests of patients already on the drug.

This sort of ethical quandary has come up for other companies, most recently Plainfield, NJ-based PTC Therapeutics, which has refused to give a boy with muscular dystrophy an experimental medicine outside of the protocol of a clinical trial.

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Genzyme has struck another big drug development partnership, this time with PTC Therapeutics, a privately-held biotech in South Plainfield, NJ. The Cambridge, MA-based biotech (NASDAQ: GENZ), the world’s largest maker of drugs for rare genetic disorders, is paying $100 million in upfront cash, plus milestone payments and royalties for the right to co-develop and co-market PTC124, an experimental drug being tested for Duchenne Muscular Dystrophy.

The deal has big dollar terms. PTC will be eligible for as much as $165 million in milestone payments from Genzyme for success in development, and another $172 million for achieving certain sales goals. The New Jersey firm will retain the right to commercialize the drug in the U.S. and Canada, while Genzyme will market it in all other countries, should it win approval; PTC will collect royalties worth a double-digit percentage of sales from countries where Genzyme sells the drug.

Why all the fuss? PTC124 is a pill with an unusual mechanism designed to block the effects of what are called “nonsense mutations” or single-point alterations in genetic code that prevent patients from making a fully functioning proteins; since these types of mutations are to blame in a number of genetic diseases, the drug could address a very broad market. The drug is currently being tested in a mid-stage clinical trial as a treament for Duchenne muscular dystrophy, and is expected to enter another mid-stage study as a treatment for cystic fibrosis, a genetic disorder that damages the lungs, by the end of the year. About 20,000 children worldwide are born each year with muscular dystrophy and few survive into their 30s, while about 70,000 people worldwide have cystic fibrosis.

“Over the past two decades, Genzyme has successfully developed four therapies for patients with severe genetic diseases. PTC124 is a powerful new approach that holds great potential to help CF and DMD patients, and many others with a variety of devastating diseases,” said Henri A. Termeer, Genzyme’s chairman and chief executive officer, in a statement. “This collaboration is an excellent strategic fit for Genzyme and will be managed within the company’s stated financial guidance.”

Genzyme’s last big deal was announced in January with Carlsbad, CA-based Isis Pharmaceuticals to co-develop mipomersen, a drug for a being tested as a treament for genetically caused form of high cholesterol that may also be used in a mass market. The PTC deal is more about going after lots of niche diseases. The compound “has the potential to address the underlying cause of disease in a subset of patients affected by more than 2,400 rare genetic disorders,” said Claudia Hirawat, PTC’s senior vice president of corporate development in a statement. We’ll dig in some more about how the companies plan to develop this drug and let you know.

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