Alnylam Pharmaceuticals has been saying for a while that it needs hard data from clinical trials to prove its skeptics wrong, and today it’s coming out with an early hint of effectiveness with its RNA interference-based treatment for lowering cholesterol.

Cambridge, MA-based Alnylam (NASDAQ: ALNY) is announcing today that it has gotten some encouraging results from a study of 20 patients who got a single shot of Alnylam’s experimental drug called ALN-PCS. This drug, designed to block the activity of a protein known as PCSK9, was able to reduce the protein by an average of 60 percent after four days when given at the highest of five doses studied. That knockdown of the specific protein translated into an average drop of 39 percent in low-density lipoprotein, the so-called “bad” form of cholesterol that clogs arteries and is known to raise people’s risk of heart attack, stroke and death.

The new drug was well-tolerated at a variety of doses, and no one has dropped out of the study because of side effects, although a mild rash was observed in patients on the treatment, the company said. The study is still ongoing, and Alnylam plans to continue examining the safety of higher doses, but the company is communicating the progress before it’s all wrapped up. Preliminary data is being presented today at the Brigham & Women’s Hospital in Boston, and more details are expected to be presented in the first half of 2012, Alnylam said. The company also plans to discuss the results in more detail on a conference call with investors today at 8:30 am Eastern time.

The data is still from the first of three phases of clinical trials normally required for FDA approval, so this drug still has years of rigorous studies to complete if it is ever going to become a new treatment for lowering cholesterol. But the market for cholesterol-lowering drugs was worth $36.4 billion worldwide last year, according to research firm IMS Health, largely because of the huge success of statin drugs. While many of those drugs are losing patents and facing cheap generic rivals, many big biotech and pharma companies (including Amgen and Sanofi) are focusing on a promising new molecular target in PCSK9, which Robert Langreth of Bloomberg News described in a November feature. Carlsbad, CA-based Isis Pharmaceuticals (NASDAQ: ISIS) also has an anti-PCSK9 product in preclinical development with Bristol-Myers Squibb.

Alnylam is wagering that while other companies are focusing on hitting this protein with genetically engineered antibodies, it will have an effective option that works through RNA interference, which specifically silences the RNA that enables the body to make the PCSK9 protein. If Alnylam can continue to show intriguing data from clinical trials (like it did last fall for a rare condition called TTR amyloidosis), it could help revive some of the enthusiasm for RNAi. Excitement for the technique once ran high because of its new ability to molecular targets that have been considered “undruggable” in the past, but enthusiasm has waned in the past couple years as big companies like Roche and Merck have curtailed their RNAi drug development activities.

The data so far for Alnylam’s PCSK9 program is still quite preliminary. Researchers randomly assigned 20 patients with … Next Page »

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Alder Biopharmaceuticals prides itself on challenging conventional wisdom. But while Alder has proved the skeptics wrong, showing it can make targeted antibody therapies in a new way with cheap and fast-dividing yeast cells, it has used this technology in a pretty conventional way—to make weapons against cancer and autoimmunity.

Now Alder is stepping out with two really unusual ideas on how to use antibodies in ways they’ve never been used before.

The Bothell, WA-based biotech company, which enticed Bristol-Myers Squibb to enter into a $1 billion partnership in 2009 to co-develop its lead drug for rheumatoid arthritis, is unveiling a couple interesting new antibodies from its discovery pipeline. These new drug candidates, which Alder is discussing today at Life Science Innovation Northwest in Seattle, are aimed at two diseases that have never been treated with antibodies—migraine headaches and high cholesterol.

The idea is to find another way to exploit Alder’s underlying technology in a place where fewer competitors tread, yet where there is still money to be made. Alder’s yeast-based system is made to be cheaper and faster at churning out antibody drugs than the usual bacterial or mammalian cells used by other companies. Partly because of the high costs of making antibodies today, most companies have developed them against diseases like cancer—where drugs can command prices of as high as $100,000. Alder’s idea is to use its more flexible platform to break out of that groove, and think about using antibodies against other chronic diseases that require lower-cost therapies.

There are still plenty of risks here, not the least of which includes whether people will pay something in the ballpark of $5,000 to $8,000 a year for a migraine treatment. Alder’s drugs are also a long way from hitting the radar of your average physician: Alder’s new migraine drug candidate is being prepped for its first clinical trial later this year, and the cardiovascular drug could enter its first human test in late 2011, or early 2012, CEO Randy Schatzman says.

Randy Schatzman

“When people typically think of antibodies in autoimmune disease and cancer, the rationale often is that these are indications in which people will tolerate the high price of those medicines, and these are indications in which people will tolerate some of the safety issues,” Schatzman says. “But we’ve been thinking, are there non-traditional markets where antibodies can play a role that people haven’t thought about in the past, but where we understand the biology?”

Migraine headaches affect an estimated 30 million people in the U.S., and nobody has ever come up with a drug that stops migraine pain before it starts. There is a family of “triptan” based drugs which generated about $3 billion in worldwide sales in 2008, although the former market leader—GlaxoSmithKline’s sumatriptan (Imitrex)—recently lost its patent and began to face generic competition.

Drugs in this class, which work by constricting blood flow to the brain, aren’t really a cure-all. They have to be taken once a patient already feels migraine pain, and then they offer some relief for half to three-fourths of patients within two hours. They don’t last … Next Page »

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The past week brought news of clinical trials and funding from drugmakers, as well as a look at venture investing strategy in health IT, and an update on the Genzyme-Sanofi buyout rumors. Catch up on those stories and more below:

—With its recently closed $523 million fund, SV Life Sciences plans to put a greater focus on investments in the health IT space, Ryan wrote. The venture firm, which has offices in Boston and the Bay Area, has so far invested in six companies developing software for the healthcare sector, including Waltham, MA-based Phase Forward (NASDAQ: PFWD). Managing partner Eugene Hill sees promise in the $17 billion that the U.S. government has pledged toward helping healthcare providers update to electronic medical records.

—Waltham-based Avedro, a biotech startup developing technology for using thermal energy in vision correction, raised $4.6 million of a planned $5 million equity, debt, and options offering. The company’s CEO was among those who pioneered the Lasik laser eye surgery technology. Avedro’s system, which doesn’t require surgery, gained European market clearance earlier this year.

—In her column this week, Sylvia took a look at the process in which the media handles news from major clinical trials and scientific breakthroughs.

—Casenet, a Bedford, MA-based maker of health management software, pulled in a $2 million debt- and options-based financing. The company raised $5 million in a similar financing last year, and nabbed a $7.5 million Series B round led by HLM Venture Partners in 2007.

—PerkinElmer, a Waltham-based research and diagnostics technology provider, acquired Bedford-based VisEn Medical. No financial details of the transaction were revealed. Company CEO Kirkland Poss and Ralph Weissleder, the director of the Center for Systems Biology at Massachusetts General Hospital, founded VisEn, which develops in vivo fluorescence imaging products.

—Ryan wrote about Vertex Pharmaceuticals’ potential blockbuster drug telaprevir, initially developed through a partnership with Eli Lilly (NYSE: LLY). The hepatitis C treatment showed … Next Page »

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Genzyme has been all over the news in the past week because of takeover speculation, but today when fundamental news came out about one of its most important assets for the future, investors yawned.

Cambridge, MA-based Genzyme (NASDAQ: GENZ) and its partner, Carlsbad, CA-based Isis Pharmaceuticals (NASDAQ: ISIS) said today that their drug for people with severely high cholesterol passed a pair of clinical trials. The drug, mipomersen, has now passed a total of four pivotal clinical trials, and the companies are preparing to seek clearance in early 2011 from regulators to start selling the drug in the U.S. and Europe.

Isis, which relies more heavily on this product for its future financial success, saw its shares drop 5 percent to $9.49 at 11 am Eastern time, while Genzyme stock dropped 1.6 percent to $69.07.

Expectations have been high for this drug to become a hit for a couple years now, as the next big thing for cholesterol after the patents expire on multi-billion dollar statin drugs such as Pfizer’s atorvastatin (Lipitor). Genzyme was said to have outhustled more than a dozen rivals that wanted to co-develop mipomersen, and it paid a whopping $325 million in upfront cash, plus $1.9 billion in potential milestone payments, (and potentially much more in future profit-sharing), to get a piece of ownership in this drug back in January 2008.

There’s so much interest for a few reasons. While statins have been used by millions of people to lower cholesterol for more than a decade, there’s a need for stronger cholesterol-lowering drugs for patients who can’t get their levels under control with conventional statins. The new drug is also based on new science, in that it’s designed to use specially engineered strands of RNA drugs to block a problematic protein in the body, which often can’t be hit by conventional small-molecule drugs. In this case, mipomersen is engineered to block the production of a protein called apoB that carries the so-called “bad” LDL cholesterol in the bloodstream. Isis CEO Stanley Crooke told me last October that mipomersen represents the third “remarkable” advance he’s seen in his 30-year career in drug development.

So what did today’s results actually tell us? The first study enrolled 58 patients who were randomly assigned to get a once-weekly injection of mipomersen, or a placebo, for about six months. The patients entered the study with severely high cholesterol—a median LDL count of 276 milligrams per deciliter of blood, even though they were already taking the highest tolerable dose of statins. By the end of the 26-week study, patients on mipomersen saw their cholesterol score drop 36 percent to a more manageable 175 milligrams per deciliter.

Still, not everybody in the trial was motivated to stick with the mipomersen regimen. Of the 39 patients who got the drug, eight dropped out of the study because of adverse events, Isis and Genzyme said. For comparison, just one of the 19 placebo patients dropped out because of an adverse event, the companies said. Researchers also saw increased levels of liver enzymes in mipomersen patients, which can be a sign of liver damage, although there were no reported cases of actual liver damage.

The second study enrolled 158 patients who weren’t as sick—they were classified merely as having a high risk of developing heart disease. More than half of the patients also had diabetes. Patients entered the study with a median LDL cholesterol score of 123 milligrams per deciliter, and when they got mipomersen, they saw that figure drop 37 percent on average to 75 milligrams per deciliter. Half of the patients got to below 70 milligrams, which is a treatment goal for high-risk heart disease patients, the companies said.

“We are pleased with the robust efficacy of mipomersen across all four phase 3 trials. These data, along with the emerging safety profile, support our focused approach on patients at highest cardiovascular risk who are in the greatest need of new treatments,” said Genzyme senior vice president John Butler, in a statement.

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Now I say this for sure, I’m not going to drop dead from a heart attack anytime soon.

Sure, I’ve seen the doctor before and had all the usual heart disease tests done—cholesterol counts, measurements of fat in the blood (triglycerides), blood pressure, the old-fashioned family history. But now I got some unequivocal signs on a high-resolution screen, which I could see in real-time, about how my arteries looked during an ultrasound scan at Bothell, WA-based SonoSite (NASDAQ: SONO).

SonoSite is pitching doctors on using ultrasound as one more tool in the endless battle to help predict, and possibly prevent, life-threatening cardiovascular events. The company is urging primary care doctors to use its portable ultrasound imaging machines to look inside a couple of arteries, to see precisely just how much plaque is building up there.

The company is so pumped about what this test can do, it invited me over to its offices last week to experience it firsthand. Even though I’m not personally worried about having a heart attack or stroke, and I certainly wouldn’t spend my own time and hard-earned money on such a test, I figured I’d give it a try because so many people are curious. Pfizer’s cholesterol-lowering drug atorvastatin (Lipitor) became the world’s best-selling drug with more than $12 billion in annual sales based on the notion that it could help people lower their risk of cardiovascular disease beyond improving their diet and exercise. In a country where junk food and the sedentary lifestyle rule, there are plenty of doctors looking for ways to strike genuine fear into patients with a new, more visual way of illustrating serious health risks. An estimated one in three people die from cardiovascular disease.

“There’s a whole community in medicine now that is serious about wanting to help people avoid a heart attack,” says SonoSite CEO Kevin Goodwin.

Kevin Goodwin

The test, which has actually been around a few years, is what’s called the Carotid Intima-Media Thickness (CIMT) exam. This is a measurement of the two inner layers of the carotid artery—an artery on each side of the neck that supplies the brain with blood. Studies over the past 20 years have shown that a thickening of this arterial wall can be an early sign of heart disease risk, at least when people are compared with peers of the same age, race, and gender.

SonoSite’s idea is to make this test fast and easy enough so that a primary care physician can incorporate it into his or her ordinary workday. SonoSite sells the doctor a $4,000 software upgrade, loaded with algorithms to analyze data on arterial thickness, and installs it on one of the company’s portable ultrasound machines. The exam itself usually takes 10 minutes or less.

Sharon Hall, one of the company’s sonographers, showed me how this works inside an exam room at the company. She ran the ultrasound probe along the right side of my neck, and then … Next Page »

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Yesterday’s FDA advisory committee meeting on Vivus’ weight loss pill proved to us, once again, how incredibly difficult it is to successfully develop and register new drugs for obesity. Mountain View, CA-based Vivus had a solid program supporting their drug—demonstrating that their combination product of phentermine and topirimate (Qnexa) is very effective and has a defined safety profile worthy of a regulatory approval. Phentermine is better known as the ‘phen’ in fen-phen, and topirimate is used for the treatment of epilepsy, migraine, and a significant amount of obesity off-label.

The good news is that the combination—tested by Vivus at three dose levels—was effective, showing a clear dose response that resulted in a median weight loss (at the high dose) of about 15 percent for patients who completed 56 weeks of treatment. That’s a serious amount of weight, considering that your average obese patients weigh around 220 pounds or more. Furthermore, the Vivus drug demonstrated some very impressive salutary effects on other endpoints that travel with obesity—including blood glucose, blood pressure, HDL and LDL cholesterol, sleep apnea, and inflammation markers.

There were some compelling speeches from patient advocates, too. I have to confess, I choked up a bit when one young and striking patient who had been transformed with tremendous weight loss during her trial experience on the Vivus drug tearfully pleaded to the panel to support approval, saying “We need help. I … need help.” She, like others who were quoted by Kelly L. Close, who edits a journal called diaTribe and spoke passionately for approval—view obesity as ‘a nightmare I cannot wake up from.”

It’s true—obesity is a lifelong struggle. She and the rest of us need to have good tools in the hands of our physicians to keep weight in check, just like we do for hypertension, high cholesterol, and other chronic diseases. It’s very touching stuff, and sobering too. Especially when you consider that 30 percent or more of U.S. adults are obese, and that the strategies being taken to stop the problem through diet and exercise are about as effective against established obesity as a sponge mop on the oil-soaked beaches of Louisiana.

So what prompted the advisory committee to vote against approval by a resounding 10-6 majority? It’s a bit of a story in itself, one that started earlier in the same room, where the fate of the diabetes drug rosiglitazone (Avandia) was discussed and vigorously debated for two days. Vivus’ Qnexa was the closing act to follow a bitterly contested decision of whether to keep GlaxoSmithKline’s Avandia on the market—a matter that was in balance due to the question of whether the drug increases risk of cardiovascular events—events that were foreseen by some and contested by others, but which took tens of thousands of patients to assess. It is painful for everyone to go back to ask if approving a drug was the right decision. Hindsight is a mean master, and the master had just taught the field a serious lesson.

What lesson? I think if one were to characterize the problem with a phrase, it would be that timeless warning made to physicians in training—”Primum non nocere,” or “First, do no harm”. Another way to say it is—be careful, and make sure you don’t make a decision you’re going to regret. Don’t end up in the same tense room 10 years later trying to figure out what, if anything, went wrong.

Yes, there were signals and other concerns with Vivus’ treatment, falling into a few main categories inherent to the two molecules packaged … Next Page »

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Things were hopping over the past week in San Diego. Get into the rhythm here.

—San Diego’s West Wireless Health Institute named Donald Casey chief executive officer. Casey was formerly worldwide chairman of Johnson & Johnson’s comprehensive care group. The Institute was founded last year with a $45 million gift from telemarketing and communications entrepreneurs Gary and Mary West.

—Tocagen raised nearly $7.8 million in a Series D round that began Feb. 2 and another $3 million from the sale of preferred shares. The San Diego biotech is working on gene therapies for cancer.

—Sapphire Energy scientists were part of research team that demonstrated the feasibility of using algae to produce commercial levels of therapeutic proteins. Sapphire cofounder Stephen Mayfield of UC San Diego believes algae will reduce the cost of producing certain biotech drugs.

—San Diego-based Trius Therapeutics, which is working on an antibiotic for MRSA infections, postponed its plan to go public. The company said it needed time to get clarity on new FDA guidelines that will affect clinical trials for its experimental drug.

—Medical device startup ImThera Medical is testing an implanted electronic device for sleep apnea. The device transmits a steady electric current that causes the tongue muscle to tighten and pull away from the upper airway. Trials are taking place in Europe.

—Isis Pharmaceuticals (NASDAQ: ISIS), a Carlsbad, CA-based biotech earned a $6 million payment from Bristol-Myers Squibb for getting clearance from regulators to begin clinical trials of a new cholesterol-lowering drug.

—Life Technologies (NASDAQ: LIFE) the Carlsbad, CA-based maker of … Next Page »

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Isis Pharmaceuticals (NASDAQ: ISIS), the Carlsbad, CA-based biotech company, said today it has earned a $6 million payment from Bristol-Myers Squibb for getting clearance from regulators to begin clinical trials of a new cholesterol-lowering drug. Isis and Bristol are collaborating on BMS-PCSK9Rx, as a targeted antisense therapy which seeks to lower cholesterol by hitting the target PCSK9.

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The big new cholesterol-lowering drug from Genzyme and Isis Pharmaceuticals, which both companies are counting on as a future profit driver, passed its first major clinical trial, but investors didn’t like what they saw when full details were released this morning at a major medical meeting.

Carlsbad, CA-based Isis Pharmaceuticals (NASDAQ: ISIS) fell 16 percent to $11.17 at 1:30 pm Eastern time after details from the trial of the drug, mipomersen, were released at the American Heart Association’s scientific sessions in Orlando, FL. Cambridge, MA-based Genzyme (NASDAQ: GENZ), which isn’t nearly as dependent on the drug, saw its shares climb 2.6 percent.

Expectations have been running high for this drug for years, with many seeing it as the next big thing for cholesterol after the invention of multi-billion dollar statin drugs such as Pfizer’s atorvastatin (Lipitor). Isis’ very bullish CEO Stanley Crooke told me last month that the drug represents an historic advance. The drug is thought to have promise because it is the first of its class that’s made of specially engineered strands of RNA drugs to block a problematic protein in the body, which often can’t be hit by conventional small-molecule drugs. In this case, mipomersen is engineered to block the production of a protein called apoB that carries the so-called “bad” LDL cholesterol in the bloodstream. The drug is originally being tested among patients with a one-in-a-million genetic condition that causes them to die young from their extremely high cholesterol, although Genzyme and Isis envision this drug becoming more widely used among wider populations of people with extremely high cholesterol that can’t be controlled by existing meds.

“Mipomersen may well be a valuable addition to the therapeutic armamentarium,” said Frederick Raal, the primary investigator of the pivotal study of mipomersen, during a webcast from today’s scientific meeting. Raal is the director of the Carbohydrate and Lipid Metabolism Research Unit at the University of the Witwatersrand in South Africa.

So what was in the data that made Isis investors, at least, skittish? First off, it should be noted that the headline results were released back in May, when Isis and Genzyme said that mipomersen reached its goal of lowering “bad” LDL cholesterol by 25 percent, compared with a 3 percent reduction on placebo, in a study of 51 patients with homozygous familial hypercholesterolemia. This meant that patients had a 100 milligram per deciliter drop in their LDL scores, which significantly lowers their risk of dangerous cardiovascular events like heart disease and stroke, Raal said. Isis and Genzyme added further detail on the effect at today’s meeting, essentially showing that secondary goals, such as lowering total cholesterol and triglycerides, also were achieved among patients on the drug.

But the treatment, which was given in a once-weekly 200 milligram injection, had some side effects worth noting. Four of the 34 patients $12 percent) who were treated with mipomersen had … Next Page »

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Isis Pharmaceuticals CEO Stanley Crooke is a man who knows how to make a grand gesture. The market may have been underwhelmed by what Isis and its partner, Genzyme, had to say about their first-of-a-kind cholesterol-lowering drug back in May, but to him that just means they’re missing the point.

When I stopped by to visit Crooke at the company’s (NASDAQ: ISIS) Carlsbad, CA, headquarters a few weeks ago to ask about his lead drug in development, mipomersen, he didn’t just offer up the usual optimistic platitudes. He said it’s going to be historic.

“In 30-plus years in drug discovery and development, I’ve been involved with 19 drugs that have made it to the market and 200 to 300 that haven’t,” Crooke says. “I’ve encountered two in my career that were amazing.”

One was cisplatinum chemotherapy for cancer. The other was cimetidine (Tagamet) for heartburn, Crooke says. “Mipomersen is the third one that’s remarkable.”

That’s a strong statement given that investors drove down Isis shares by 10 percent on heavy volume on May 20, after seeing their first glimpse of data from a pivotal trial of mipomersen. Expectations have been sky-high for this drug for a couple years now, as the next big thing for cholesterol after the invention of multi-billion dollar statin drugs such as Pfizer’s atorvastatin (Lipitor). Cambridge, MA based Genzyme (NASDAQ: GENZ) was said to outmaneuver more than a dozen rivals that wanted to co-develop mipomersen. In January 2008 Genyzme paid the princely sum of $325 million in upfront cash, plus $1.9 billion in potential milestone payments, (and potentially much more in future profit-sharing), to get a piece of ownership in this drug.

Stanley Crooke

Mipomersen has generated so much interest for at least a couple big reasons—the need for more powerful cholesterol-lowering drugs for patients who can’t get those levels under control with conventional statins, and because it represents a potential standard-bearer for Isis’ antisense technology. It’s designed to use specially engineered strands of RNA drugs to block a problematic protein in the body, which often can’t be hit by conventional small-molecule drugs. In this case, mipomersen is engineered to block the production of a protein called apoB that carries the so-called “bad” LDL cholesterol in the bloodstream.

In May, Isis and Genzyme declared victory in a press release that announced the first pivotal clinical trial of mipomersen. The companies said that of 51 patients with a rare genetic abnormality called homozygous familial hypercholesterolemia that causes high cholesterol, the drug was a success. Patients on mipomersen had a 25 percent reduction in their LDL cholesterol counts, compared with a 3 percent drop for those on a placebo. The drug also reached its secondary goals, including showing an apoB protein reduction which correlated with the cholesterol-lowering—an important point for scientists and physicians.

But the market didn’t see it as reason to cheer. Patients with this genetic abnormality are seriously ill, with LDL cholesterol scores at an eye-popping 400 milligrams per deciliter of blood when they entered the study. (Anything below 200 is considered desirable, according to the Mayo Clinic).

So simple math says that a 25 percent reduction from 400 takes those patients down to about 300, which might be good, even unprecedented for such sick patients, but it’s still not what most patients and doctors would consider healthy. Plus, there were six patients who didn’t complete their course of treatment after they were enrolled in the study, which certainly didn’t help.

So why was Crooke so enthused? He walked me through some of the context around the data that will be presented next month at the American Heart Association’s scientific sessions in Orlando, FL.

What’s remarkable, Crooke says, is that mipomersen works in every animal, and in every … Next Page »

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Oscient Pharmaceuticals has apparently run short on options to keep its struggling drug business afloat. The Waltham, MA-based biotech firm (NASDAQ:OSCI) and its subsidiary Guardian II Acquisition Corporation have each filed for Chapter 11 bankruptcy protection and Oscient has landed a buyer for one of its two marketed products, Oscient announced late yesterday.

The company says it has struck an agreement to sell its assets associated with the antibiotic drug gemifloxacin mesylate (Factive), to a subsidiary of Cary, NC-based Cornerstone Therapeutics (NASDAQ:CRTX) for more than $5 million. Yet it’s expected that there will be a competitive auction for the Factive assets in bankruptcy court before the deal is sealed. The antibiotic, which treats forms of bronchitis and pneumonia, accounted for only $16.5 million of Oscient’s $86.8 million in 2008 revenue. The firm is also seeking a buyer for its top-selling drug, fenofibrate (Antara), which is prescribed for patients with above-normal cholesterol and triglyceride levels.

Oscient appears to be the latest victim of a lousy environment for unprofitable life sciences companies searching for funds to stay alive. Other local examples include Waltham, MA-based drug developer Dynogen Pharmaceuticals, which filed for bankruptcy early this year, and synthetic DNA maker Codon Devices, which reportedly shuttered its operations in Cambridge, MA, this spring. The cash shortage has also prompted Lexington, MA-based Epix Pharmaceuticals (NASDAQ:EPIX) to sell off assets and seek other alternatives to stay afloat.

Oscient, which plans to continue operations while in bankruptcy, has racked up $183.3 million in debts and has assets valued at $174 million, according to its bankruptcy filing. The filing says that the company owes $46 million to U.S. Bank National Association, of Boston, $7.8 million to funds associated with Dallas-based investment firm Maverick Capital, $6.6 million to BB Bioventures in South San Francisco, and $5.5 million to medical products giant Abbott Labs, headquartered in Abbott Park, IL, to name its four largest creditors listed in the bankruptcy filing.

The bankruptcy filing is the latest measure Oscient has taken to keep its business intact. The company cut about 100 of its some 300 workers in February to save money, and last month it said it planned to slash another 180 jobs, including its entire 150-person sales force. Still, the company said last month that it only had enough cash to operate into the third quarter of 2009. Also, the Nasdaq plans to de-list Oscient’s common stock later this month for the company’s failure to pay fees to meet its listing obligations, according to the company.

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[[Update below]] Genzyme and Isis Pharmaceuticals have bet big on a new kind of cholesterol-lowering drug, and today the companies said it worked in a pivotal clinical trial.

Mipomersen, a drug designed to block production of a protein that carries LDL cholesterol in the blood, reached its goal in a study of 51 patients with a rare genetic abnormality called homozygous familial hypercholesterolemia, that gives them extremely high cholesterol. Patients on the new drug had a 25 percent reduction in their LDL cholesterol counts, compared with a 3 percent drop for those on placebo, and the difference was statistically significant. Full data will be presented later at a medical meeting, the companies said.

The news is important to Cambridge, MA-based Genzyme, because it is carrying out a plan to apply for FDA approval of mipomersen first in this small patient population of 500 or so, while also studying it in much larger groups of patients that might turn the product into a blockbuster. For Carlsbad, CA-based Isis Pharmaceuticals, it’s an important validation of its antisense technology, in which specially engineered strands of RNA drugs are designed to block a problematic protein in the body, which often can’t be blocked by conventional small-molecule drugs. The companies struck a partnership to co-develop the drug in January 2008, which brought $325 million in upfront cash to Isis, and could be worth as much as $1.9 billion to Isis if the drug achieves certain goals in development.

“These are promising results for a very high-risk patient population that is in great need of new treatment options,” said Genzyme chief medical officer Richard Moscicki, in a statement. “This is one of the largest studies of hoFH patients ever conducted, and we are very encouraged by these robust data and the emerging profile of the drug. With these results, we remain on-track with our development plan for mipomersen.”

Besides reaching its main goal of lowering LDL cholesterol, mipomersen achieved all three of its secondary goals in the study of reducing the apoB protein it’s supposed to block, lowering total cholesterol, and non-HDL cholesterol, the companies said. The company said it plans to submit the data to the FDA for approval in the second half of 2010, by which time it hopes to have data from larger trials of mipomersen in other types of patients with high cholesterol.

The most common side effects among the 34 patients who got mipomersen were flu-like symptoms, swelling near the injection sites, and an increase in liver enzymes. One patient dropped out of the study because of an increase in liver enzymes, which can be a sign of liver damage. Patients had to take 200 milligrams of mipomersen through weekly injections for about six months.

Patients entered the study quite sick. They had an average LDL cholesterol score of 400 milligrams per deciliter of blood, even though they were already taking the highest possible dose of the common statin medicines, and other drugs to lower fats in the bloodstream. Any total cholesterol score above 240 is considered high, and anything below 200 is considered desirable, according to the Mayo Clinic.

[[Update 11:15 am Eastern time]] A 25 percent average reduction in LDL scores would bring patients in this study down to an average score of 300 milligrams per deciliter, which for most people is still considered high. Some patients in the trial had their LDL counts drop much more than 25 percent, although those detailed results aren’t being released yet, says Isis spokeswoman Amy Blackley. “There were some really high reductions,” Blackley says.

A previous study showed the drug could lower cholesterol by an average of 49 percent—better than results announced today—but that was in just eight patients, and they took a higher 300 milligram dose, said Isis spokeswoman Amy Blackley. The pivotal study announced today was designed to show at least a 20 percent reduction, and cleared that average hurdle, even when handicapped by factoring in six patients who enrolled but didn’t complete their course of treatment, Blackley says.

“These are patients who are on everything and they still can’t get their LDL down. If you can get it down by 100 points, that’s phenomenal. There’s nothing else for them,” she says.

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Genzyme (NASDAQ:GENZ) and Isis Pharmaceuticals (NASDAQ:ISIS) say the biotech firms have begun two new late-stage clinical trials and have started screening patients for a third new study of cholesterol-lowering drug mipomersen, aiming to ratchet up the amount of data on patients treated with the drug over the next 18 months. Luke caught up with Cambridge, MA-based Genzyme last year to discuss the large biotech firm’s foray into the multibillion-dollar market for drugs that lower cholesterol with mipomersen-developer Isis, headquartered in San Diego.

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Genzyme has built an empire by thinking small—treating diseases that affect tiny groups of patients. Now it’s seeking to capitalize on a cholesterol-lowering drug that requires it to think small and big at the same time.

The Cambridge, MA-based biotech company (NASDAQ: GENZ) is starting to show how it intends to make mipomersen into a workhorse for much of its growth over the next decade. I got some insight into the company’s thinking during an interview with John Butler, president of the company’s renal, endocrinology, and cardiovascular business.

Genzyme placed a big bet on mipomersen back in January, when it agreed to pay $325 million upfront to Carlsbad, CA-based Isis Pharmaceuticals (NASDAQ: ISIS) for the right to co-market the drug worldwide. The price for a piece of mipomersen was high for a couple reasons. Soaring cholesterol levels in the fast-food-loving U.S. contribute to heart disease, the nation’s leading cause of death. And drugs that lower cholesterol are the best-selling class of pharmaceutical products, generating 79 million prescriptions a year, according to market research firm IMS Health. Pfizer’s Lipitor, the leader of the class, is the top-selling pharmaceutical ever, with $12.7 billion in sales last year. So anything that comes along that’s more effective, even if it grabs only a sliver of this market, is going to generate serious cash flow.

That’s exactly what Genzyme is banking on. “This offers a significant benefit over the standard of care for a seriously ill patient population. We look at this as a significant driver for us in the future,” Butler says.

A clinical trial last year showed that mipomersen could reduce cholesterol by 40 percent more than statins alone, that it can lower patients’ cholesterol counts to a safe level, and that it can be taken in combination with those drugs. Sounds great, but as Butler says, this isn’t really for everybody. The new drug is only meant to be taken by patients at exceptionally high risk of heart attacks and strokes because of their clogged arteries. Plus, since it’s a weekly injectable, it doesn’t have the same kind of convenience for the masses as a daily pill like Lipitor. (The drug also is designed to work differently than anything on the market. It’s a targeted drug that reduces the production of apoB-100, a protein that’s essential for synthesizing and transporting LDL “bad” cholesterol in the blood.)

“This is not a product that will compete with statins, it’s for patients who aren’t adequately controlled with those drugs,” Butler says.

Mipomersen isn’t scheduled to reach the desk of FDA reviewers until the second half of 2010, so a lot of work still needs to be done to prove it’s ready for the market. Genzyme’s first item on its to-do list is to show that mipomersen works for patients with an extremely rare genetic disorder called homozygous familial hypercholesterolemia that makes it so people can’t properly control cholesterol in the blood. The disorder means that patients have two faulty copies of a gene that controls cholesterol levels, which puts even very young children at risk of a heart attack or stroke, Butler says. About 300 patients, one in a million people in the U.S., have this disorder, and Genzyme expects to be able to ask the FDA for clearance to sell the drug in the second half of 2010 if this trial pans out, Butler says.

That targeting of a small patient population is typical Genzyme. But here’s where the part about thinking bigger enters the picture: … Next Page »

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Cambridge, MA-based Genzyme (NASDAQ: GENZ) and its partner, Carlsbad, CA-based Isis Pharmaceuticals (NASDAQ: ISIS), said today they have started a pivotal clinical trial for patients with a genetic disorder that causes exceptionally high levels of cholesterol. The study will enroll 100 patients in the U.S. and Canada, to take 200 milligrams of the experimental drug mipomersen or a placebo each week for about six months. Data from the trial, the first of four new studies the companies plan to initiate by year’s end, will be available in 2010.

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The FDA gave MediQuest Therapeutics a boost today. MediQuest, the developer of a treatment for Raynaud’s disease, a painful condition of the hands and feet, said the FDA has agreed to give its drug application an expedited 6-month review since it can treat an unmet medical need. The agency usually takes 10 months to consider an application, particularly if it’s the fourth or fifth in a class of well-known drugs, like statins for lowering cholesterol.

MediQuest, a privately-held company in Bothell, WA, turned in its application to U.S. drug regulators in April. That means the firm may learn as soon as October whether it can make the leap from being solely a developer of new drugs to being a company that also has a product to sell. If approved, the drug would also be the first product specifically for Raynaud’s.

The drug (formerly dubbed Vascana in company statements, now being called MQX-503), is a topical formulation that patients can rub on their hands or feet to prevent or treat the symptoms of a painful Raynaud’s flare-up. About 2.1 million people are estimated to have sought medical treatment for the disease, and about 90 percent are women, MediQuest has said. How many of them may seek out MediQuest’s therapy is the burning question.

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Cambridge, MA-based Genzyme and Isis Pharmaceuticals said today they have modified some of the terms of their partnership to develop Isis’s mipomersen for patients with high cholesterol. The deal, originally announced with a bang in January, still provides $325 million in upfront payments to Carlsbad, CA-based Isis for the antisense RNA-based drug, although it now shifts $50 million more of the drug’s development costs to Isis.

Three months after the original deal was struck, investors in the companies got a bitter pill. The FDA asked Isis (NASDAQ: ISIS) for more study data that is expected to delay the drug’s market application for a year, until 2010. That sent Isis stock plunging 29 percent that day, April 25. Genzyme (NASDAQ: GENZ) will now take the lead on future discussions with regulators, the companies said.

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