[Updated: 8:45 am PT] Onyx Pharmaceuticals has set its sights on shaking up the standard of care for a deadly cancer of the bone marrow, and now results from at least one small study suggest it has a shot.

Researchers are reporting today that when the experimental treatment from South San Francisco-based Onyx (NASDAQ: ONXX) was combined into a three-drug regimen, it increased the odds that multiple myeloma patients would see a significant shrinkage of their tumors, without the nerve damage in fingers and toes that limits dosing of the existing standard of care. The study looked at 53 patients getting their first round of therapy for multiple myeloma with a combination of Onyx’s carfilzomib, Celgene’s lenalidomide (Revlimid), and low-dose dexamethasone.

Many details of the trial were released last month on the American Society of Hematology’s website, and they will be formally discussed further at 5:45 pm Eastern/2:45 pm Pacific time today in an oral presentation at the organization’s annual meeting in San Diego.

“We now have a regimen which is well-tolerated, efficacious, and can be used for an extended period of time with limited need for dose [adjustments],” says Andrzej Jakubowiak, the director of the multiple myeloma program at the University of Chicago Medical Center, and the study’s lead investigator. “The results were beyond my expectations.”

The new batch of results is still preliminary, and there was no control group, so it’s impossible to say how well the Onyx drug is performing compared to other treatments. Still, it could have big implications for Onyx’s business and that of its primary competitor—Cambridge, MA-based Millennium: The Takeda Oncology Company. Onyx is seeking FDA approval of carfilzomib, at least initially, as a treatment for the very sickest of patients who have relapsed and developed resistance against other treatments. But because the Onyx drug—a proteasome inhibitor like Millennium’s—has shown strong effectiveness combined with a milder effect on peripheral nerves, researchers have long been curious about its potential to go beyond the sickest patients, and offer a new option for the larger group of newly diagnosed patients.

Still, shares dipped 5 percent to $38.33 at 11:41 am Eastern today, after Onyx said the FDA has declined to provide  a faster-than-usual six-month review of the new drug, which the agency sometimes grants to groundbreaking therapies. The FDA’s deadline to complete its review of the Onyx application is set for July 27th.

About 20,000 people are diagnosed with myeloma each year in the U.S., and 10,000 die from it annually, according to the American Cancer Society. Millennium: Takeda’s drug bortezomib (Velcade) became a billion-dollar annual blockbuster by advancing the standard of care in these patients, so if Onyx can deliver comparable or better clinical results, it has an opportunity to tap a very big market.

“While development in this setting [front-line therapy] is still in early stages, we think it looks promising and is a major driver of investor optimism for the long term future of carfilzomib,” said Cory Kasimov, an analyst with JP Morgan, in a note to clients Dec. 4.

Here’s what the researchers found: When patients went on the three-drug combo that included the new Onyx treatment, 46 of 49 people (94 percent) had their tumors shrink at least by half within the first month. That number climbed to 100 percent after four months, and stayed … Next Page »

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Cambridge, MA-based drug developer Tensha Therapeutics announced today that it has snapped up $15 million in Series A funding from HealthCare Ventures. The funding will go to developing Tensha’s small molecule drug candidates, which are designed to treat cancer and other diseases by regulating the expression of disease-associated genes.

Tensha’s drugs are inhibitors of so-called bromodomains, protein modules that are key players in epigenetics—the process of turning genes on and off without altering the underlying DNA code. Tensha has an exclusive license from Dana-Farber Cancer Institute to technology developed by one of its investigators, James Bradner, who identified and characterized small molecule inhibitors of certain bromodomain proteins that are key to cancer cell growth, according to today’s announcement. Tensha’s lead drug program is in pre-clinical development for treatment of a rare cancer called BRD4-NUT midline carcinoma, acute myeloid leukemias, multiple myeloma, and other diseases.

“There is a compelling biological rationale for bromodomain inhibition in cancer. Our collaborative studies to date have established the feasibility of targeting epigenetic reader proteins. Through Tensha, we have a foundation for developing and translating novel bromodomain inhibitors,” said Bradner in the announcement of the deal.

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[Update: 9:20 am ET] Dendreon ran into a buzz saw of opposition last year when it priced its new prostate cancer drug at $93,000 per patient. Genentech has loads of critics who say it has overreached on price with its antibody drugs for cancer, especially in cases where the data supporting the drug is controversial, as with bevacizumab (Avastin) for breast cancer. But despite all the pressure from insurers, elected officials, patients, and doctors, drugmakers are showing no signs of backing off.

Many times, I’d say the critics are right to complain about excessively high drug prices. But in a few cases, the drugmakers are right to stand firm, and today we’re going to see an interesting test case.

Today, we’ll see a new player emerge in the great cancer drug price debate: Seattle Genetics (NASDAQ: SGEN). The company won FDA clearance on Friday to start selling its new antibody drug for Hodgkin’s disease and another rare lymphoma. [Updated 9:20 am ET, with pricing info] Seattle Genetics revealed the price of this new drug, called brentuximab vedotin (Adcetris), on a conference call with analysts this morning. The company set the price at $13,500 per dose, given intravenously every three weeks. If patients get eight infusions on average, consistent with clinical trial experience, then it will cost $108,000 per patient. Wall Street was expecting it to cost about $109,800 per patient for a course of treatment, based on the average estimate of five Wall Street analysts I surveyed last week.

Most Americans will never make that much money in a single year of their life, so this could be an easy target for critics of high drug prices. But this is one case in which a drug is worth a six-figure price tag.

Here’s why: For starters, the Seattle Genetics drug is being aimed at a small group of patients. About two-thirds of the 8,500 patients diagnosed in the U.S. with Hodgkin’s disease are successfully treated with chemotherapy, leaving about one-third who eventually get relapsed, treatment-resistant forms that make them candidates for the Seattle Genetics drug. The other group of anaplastic large cell lymphoma patients who are eligible is even smaller. Insurance companies do most of their watchdogging on price with much more common medicine. They usually, or at least should, have better things to do than mess with a tiny handful of customers in their risk pool.

Those who are afflicted with this disease aren’t just dealing with some minor annoyance, or theoretical risk. Many patients with relapsed Hodgkin’s disease are in their primes (their 30s and 40s), and are being threatened with an illness that offers a life expectancy of just two to three years. These patients have no other options left. The Seattle Genetics drug is bringing innovation to a moribund field of cancer drug development. It is the first product approved for Hodgkin’s disease since 1977, and the first ever for anaplastic large cell lymphoma.

And most importantly, the data to support this drug’s approval was simply superb. About 75 percent of patients with Hodgkin’s disease had significant tumor shrinkage, and 86 percent did that well with anaplastic large cell lymphoma (ALCL). About a third of the Hodgkin’s patients and more than half of the ALCL patients went into complete remissions. These are the kinds of tumor shrinkage rates that you rarely see in the cancer drug business.

There’s no major rub here in terms of side effects, which are pretty typical for other compounds in this drug’s class. Patients get depletion of infection-fighting white blood cells, nerve damage in the fingers and toes, fatigue, nausea.

One big question here is still about survival. Nobody knows … Next Page »

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Tony Coles was about nine years old when he decided to become a doctor. His father, a government accountant and a minister, told him that medicine and law were great professions. The younger Coles, a fan of math and science, opted for medicine. And even when teachers underestimated him, placing Coles in a math class that he thought was too slow and boring, he kept his eye on the prize.

“I just held onto that belief that I could be a doctor,” Coles says. “It’s funny how these things can become self-fulfilling prophecies. I don’t believe things happen by accident. I was destined to be involved in some way in healthcare.”

Coles, now 51, has put himself into a position to make an even bigger impact on healthcare than a lone physician can, as the CEO of South San Francisco-based Onyx Pharmaceuticals (NASDAQ: ONXX). The company already has developed a drug for kidney and liver cancer that’s approaching $1 billion in worldwide sales, and Coles is now attempting to pull off Onyx’s second act, by winning FDA approval of a second product with billion-dollar potential for treating a type of cancer called multiple myeloma. If Coles can lead Onyx through this journey to become a two-product company, a transition few biotechs ever complete, then it should be in position to control of its own corporate destiny for a long time.

Coles, who signed on as Onyx as CEO in February 2008, will draw on all his various experiences from his upbringing and his career as a physician and pharma executive to make this happen. Hollings Renton, who retired three years ago to bring Coles on board, says his successor has the focus it will take for Onyx to rise to a new level.

“Tony had all the right experience,” Renton says. “He’s had senior level executive positions in pharma and biotech, a heavy duty commercial background, and also a medical background. He’s a very, very clear strategic thinker. I just saw leadership. And he’s a values-based guy, cares about people, and is very empathetic. I thought he would do the right things.”

Coles also happens to be African American in an industry with very few people with his skin color. So by definition, he’s had a lot of experiences that most people in the business have only read about.

He started on his path growing up in a middle-class family in Washington D.C., the oldest of three siblings. His father, as mentioned above, was an accountant who worked for the federal government. Coles’ mother was an office manager who worked for what is now AT&T. His parents were products of the great migration, as many African Americans fled the Jim Crow south in the first part of the 20th century to seek more opportunity in major cities of the north. They instilled at least … Next Page »

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Onyx Pharmaceuticals is betting that it can keep growing on the strength of a new cancer drug that’s supposed to compete with a blockbuster from Cambridge, MA-based Millennium: The Takeda Oncology Company. Today, Onyx is presenting key data to gird for the market battle.

Onyx, the Emeryville, CA-based biotech company (NASDAQ: ONXX), is reporting today on a clinical trial of 266 patients that shows its lead cancer drug in development, carfilzomib, shrank tumors by at least half in 24 percent of the sickest patients with multiple myeloma, a deadly cancer of the bone marrow. About one-third of these patients saw what was considered a clinical benefit, while two-thirds didn’t. The remissions lasted a median time of 8.3 months, and patients had a median overall survival time of 15.5 months.

These patients weren’t randomly assigned to another treatment option, so it’s impossible to say how much better this drug is compared to another round of currently available therapies. But previous studies suggest that patients this sick-whose disease had only worsened after a median of five rounds of therapy—had a life expectancy of about six to nine months, says David Siegel, a myeloma specialist at Hackensack University Medical Center in New Jersey, and an investigator on the study. He is presenting the data today at the American Society of Hematology meeting in Orlando, FL.

“The patients in this trial were rapidly approaching the end of their lives, and we saw some incredibly deep and durable responses in patients for whom we had no reason to expect that,” says Siegel. “Unabashedly, I love this drug and I can’t wait for it to be approved.”

About 20,000 patients are diagnosed in the U.S. with myeloma each year, and about 10,000 die from it, according to the American Cancer Society.

Onyx’s findings shouldn’t be much of a surprise to investors, since the company reported on the basic overall tumor shrinkage rate back in July. What’s new and meaningful today is how long the remissions lasted, the survival times, and the side effects.

Before going into the clinical details, first a little background. Like Millennium’s $1 billion blockbuster, bortezomib (Velcade), the Onyx drug is a proteasome inhibitor. Millennium blazed this trail almost a decade ago, showing that if you can make a drug to inhibit these enzymes that act as a cellular garbage disposal, you could fight cancer a novel way. The idea was to block the release of certain proteins that cancer cells secrete to grow and resist conventional chemotherapies.The Millennium drug has shown an impressive ability to shrink tumors of multiple myeloma patients, and its wide adoption, along with a different product from Celgene, lenalidomide (Revlimid), is widely credited among doctors with helping make myeloma more like a chronic disease than a near-term death sentence.

The catch, and there is always is one in the pharma business, is in the side effect profile. Most patients on the Millennium drug get … Next Page »

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London-based GlaxoSmithKline has terminated a mid-stage clinical trial of SRT501 in patients with advanced multiple myeloma, the company said in a statement e-mailed to Xconomy today. The firm acquired the drug, a formulation of resveratrol, in its $720 million buyout of Cambridge, MA-based Sirtris Pharmaceuticals in 2008.

Sirtris has captured wide media attention because of the potential anti-aging benefits of the naturally occurring chemical resveratrol, which can be found in the skin of red grapes and in red wine.

Glaxo decided to end the trial after a review of data from the study found that the formulation of resveratrol “may only offer minimal efficacy while having a potential to indirectly” cause kidney complications that often occur in myeloma patients, according to the company’s statement. The Myeloma Beacon first reported the news about the recent decision to terminate the trial yesterday. Multiple myeloma is a type of cancer found in plasma cells.

The Phase IIa clinical trial tested the use of SRT501 with and without the approved cancer treatment bortezomib (Velcade), according to the government’s clinical trials website.

Glaxo had suspended enrollment of the study in April of this year after cases of acute kidney failure were found in five study patients, according to the company. In the company’s analysis of these cases, it “concluded that these renal failure cases were most likely due to the underlying disease, as kidney complications related to myeloma occur in up to 50 [percent] of cases. However, the formulation of SRT501 was not well tolerated, and side effects of nausea/vomiting/diarrhea may have indirectly led to dehydration, which exacerbated the development of the acute renal failure,” the company said.

Glaxo, which continues to operate Sirtris as its subsidiary in Cambridge, said that it is now focusing on “selective SIRT1 activator compounds that have no chemical relationship to SRT501 and more favorable drug-like properties.” Those selective activators include compounds known as SRT2104 and SRT2379.

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Some minor bad news came out this afternoon from Onyx Pharmaceuticals, and its lead drug candidate for patients with multiple myeloma.

The Emeryville, CA-based drug developer said today it is delaying the new drug application for carfilzomib after FDA officials asked for more data to show it can manufacture larger commercial batches that are consistent with the molecules it produced and tested in clinical trials. Onyx (NASDAQ: ONXX) had previously forecasted it would turn in the application by the end of 2010, and now says it will come “as early as mid-year 2011.”

“This is a timing issue,” Onyx CEO Tony Coles said today on a conference call with analysts. “We believe the fundamental value proposition for carfilzomib is unchanged and the commercial opportunity is significant.”

The FDA’s request for more data came after the company made some modifications to its manufacturing process as it attempts to start scaling up for commercial demand. The company saw some “minor variations” that are thought to be related to minor changes in equipment temperatures at the larger scale. Onyx has generated some data already, and is working to produce more, to show its larger-scale process is reproducible and creates a product with the same properties that were observed in the clinical trials.

The new drug is vitally important to Onyx’s growth prospects, as it seeks to diversify beyond its lone marketed product at the moment, sorafenib (Nexavar) for kidney and liver cancer. Onyx agreed to pay $276 million upfront, plus another potential $535 million in milestone payments to obtain carfilzomib last year through the acquisition of South San Francisco-based Proteolix. A few months later, in July, Onyx reported that the new drug helped shrink tumors in about one-fourth of patients who had relapsed after getting prior rounds of treatment. The results were compelling enough to seek FDA approval, even though the drug hasn’t yet completed the third and final stage of clinical trials usually required before a drug can be sold in the U.S.

If the drug is approved, it would be a new treatment option for a disease that hits about 20,000 people each year in the U.S., and kills about half that many every year, according to the American Cancer Society.

Onyx shares fell about 7 percent in after-hours trading following news of the delay.

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Onyx Pharmaceuticals has found a new partner to help sell its lead drug candidate for multiple myeloma in Japan, less than two months after it unveiled some promising clinical trial results.

The Emeryville, CA-based developer of cancer drugs (NASDAQ: ONXX) is announcing today that it has struck a new partnership with Japan-based Ono Pharmaceutical, in which Onyx will get about $59 million in upfront cash and potentially another $280 million in development and milestone payments based on today’s currency exchange rates. In return, Ono will get exclusive rights to develop and commercialize two Onyx drugs for cancer patients in Japan. The deal includes Onyx’s lead drug candidate, carfilzomib for multiple myeloma, as well as another drug at an earlier stage of development for the same condition, called ONX 0912.

The deal comes a little more than six weeks after Onyx released results from a mid-stage clinical trial that said carfilzomib was able to at least partially shrink tumors in one-fourth of patients with multiple myeloma and keep them in check for a median time of seven months—even when patients were so sick they had essentially run out of other options. Onyx had told investors it would seek a partner in Asia to help commercialize the drug there, but it has retained full ownership rights in the U.S. and Europe. The company is now in the midst of preparing a new drug application to the FDA, which it plans to turn in by year’s end.

“This is a Japan-only deal, and it’s a very valuable one,” says Onyx CEO Tony Coles. He noted that the latest round of clinical trial results strengthened his company’s bargaining position. “The results reinforced [Ono's] commitment to the compound,” he says.

Onyx, as I noted in a story back in July, has been seeking for some time to diversify itself beyond its current position as a one-drug company driven by sorafenib (Nexavar). That drug, approved by the FDA for kidney and liver cancers, generated $843 million in sales last year for Onyx and its partner, Bayer. But Onyx sought to expand its horizons, specifically through last year’s the acquisition South San Francisco-based Proteolix for $535 million. That deal gave Onyx full worldwide ownership of carfilzomib, an intravenously delivered therapy for multiple myeloma.

What few people noticed at the time was that Onyx also acquired an oral pill … Next Page »

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This week we had reports from a couple of the leading biofuel companies in the Bay Area, along with a noteworthy advance from a cancer drug developer.

—LS9, the South San Francisco-based biofuel company, reported in this week’s edition of Science magazine how it discovered genes in cyanobacteria that it hopes will pave the way to its goal of $50 per barrel oil from renewable sources. The company described how these genes, when inserted into E. coli bacteria, can convert sugars into alkanes (a key component of fuel) in a one-step biological process.

—I talked with Jonathan Wolfson, the CEO of another one of aspiring biofuel players in South San Francisco, Solazyme, in an in-depth profile. This conversation covered a lot of ground about how the company got started, switched gears early on, and now is seeking to gain the first-mover advantage by producing greater quantities of renewable fuel than its peers.

—Gilead Sciences (NASDAQ: GILD), the world’s largest maker of HIV drugs, said this week it is borrowing $2.2 billion, and planning to use much of that money to buy back shares of stock. Shares of Gilead traded today a little over $33, a long shot from its 52-week high of $50.

—Emeryville, CA-based Onyx Pharmaceuticals reported results from a mid-stage study of 266 very sick patients with multiple myeloma, a cancer of the bone marrow. The Onyx drug appeared to at least partially shrink tumors for one-fourth of these patients, who had relapsed after multiple prior rounds of treatment. The company (NASDAQ: ONXX) said the results are promising enough that it plans to seek FDA approval before the end of the year.

—We also had a couple of solid guest editorials from authors outside of San Francisco who wrote about issues of great interest to the local biotech community. Steve Speer, a biotech consultant in Carlsbad, CA, discussed why corporate frugality isn’t always the best way to conserve cash. And Daniel MacArthur, an ace genomics blogger and researcher at the Wellcome Trust Sanger Institute in the U.K., talked about how direct-to-consumer genetics companies like 23andMe and Navigenics got beat up pretty good at a congressional hearing last week, and how this could have some damaging consequences for this fledgling industry.

If you have any issue you’d like to write about for the San Francisco, or national biotech communities, please send me a note at ltimmerman@xconomy.com or reach out to Xconomy San Francisco editor Wade Roush at wroush@xconomy.com.

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Tony Coles has been pushing for two years to re-fashion Onyx Pharmaceuticals into more than a one-drug company, and now he might have the data to make that happen.

The Emeryville, CA-based biotech company (NASDAQ: ONXX) is announcing today that its drug candidate for multiple myeloma was able to at least partially shrink tumors for about one-fourth of patients who were so sick they had essentially run out of other options. Those fortunate enough to respond to therapy stayed in remission a median time of 7.4 months. Side effects—such as pneumonia, anemia, and depletion of infection-fighting white blood cells—were consistent with findings from a previous study. The evidence from the latest trial of 266 patients was strong enough that Onyx plans to use the data to seek FDA approval for its drug, carfilzomib, before the end of this year.

Onyx has been built on the back of one hit drug for kidney and liver cancer, sorafenib (Nexavar), which generated $843 million in sales last year for Onyx and its partner, Germany-based Bayer. Onyx has been seeking to diversify its portfolio for years, and made an aggressive move last October when it agreed to acquire South San Francisco-based Proteolix for as much as $535 million to obtain whole ownership of carfilzomib. About 20,000 people get diagnosed with multiple myeloma, a cancer of the bone marrow, each year in the U.S., and about 10,000 people die from the disease annually, according to the American Cancer Society.

Multiple myeloma therapy is dominated today by Cambridge, MA-based Millennium: The Takeda Oncology Company and Summit, NJ-based Celgene. Onyx is hoping this new set of results in the sickest patients will help it capture some significant share of a worldwide market that’s worth an estimated $4 to $5 billion a year, and still growing.

“This data really validates our growth strategy, and the acquisition of Proteolix,” Coles says.

Tony Coles

Only a portion of the data is being made public to investors today, and much more detailed information will have to come later at a medical meeting or in a peer-reviewed journal. So there is plenty of room for skeptics to question the results being announced today, or at least reserve judgment for a later time.

That said, here’s the gist of what Onyx is reporting. This trial enrolled 266 patients who had previously relapsed and stopped responding to a median of five prior courses of therapy that usually included Millennium’s bortezomib (Velcade), Celgene’s lenalidomide (Revlimid), and dexamethasone, a common anti-inflammatory drug. Based on historical records, patients this sick were expected to respond to therapy about 11 percent of the time, and have a life expectancy of about six to 10 months.

These patients’ last hope was essentially to enroll in the Onyx study, in which they got regular intravenous infusions with carfilzomib. The Onyx drug, like Millennium’s treatment, is what’s known as a proteasome inhibitor. Millennium blazed this trail almost a decade ago, showing that if you can make a drug to inhibit these enzymes that act as a cellular garbage disposal, then you might block the release of certain proteins that cancer cells secrete to grow and resist conventional chemotherapies.

Because the patients who enrolled in this study were extremely sick, and had already cycled through all the other therapies, the trial was designed to simply enroll patients on the Onyx drug without randomly assigning them to a placebo or any other drug that could offer a comparison.

Heading into this study, Onyx said it was hoping to see at least … Next Page »

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[Updated: 6 pm Eastern] Bad news out of Seattle-based Oncothyreon (NASDAQ: ONTY) today. The company’s partner, the Merck Serono unit of Germany-based Merck KGaA, has halted clinical trials of an immune-boosting treatment for cancer after it saw an unexpected inflammation of the brain in a patient who joined an exploratory trial. Shares of Oncothyreon fell 29 percent on the news.

The FDA has placed the development program for the BLP25 liposomal vaccine (Stimuvax) on a clinical hold, which means all clinical trials of the experimental drug are on hold until researchers can determine whether it’s safe to start them up again. The suspension affects two lung cancer trials known as Start and Inspire, as well as a breast cancer study called Stride. Those are large, pivotal trials that enroll a combined 2,600 patients.

The patient in question developed encephalitis, or inflammation of the brain, in an exploratory trial of Oncothyreon’s vaccine, the company said. The study was investigating the vaccine’s mechanism of action and how it works in combination with cyclophosmide chemotherapy. The patient has multiple myeloma, a cancer of the bone marrow.

“Patient safety is of paramount importance to Merck Serono and to Oncothyreon,” said Oncothyreon CEO Bob Kirkman, in a statement. “We understand that Merck Serono is working closely with the FDA, other regulatory agencies and the patient’s physicians to evaluate the implications of this adverse reaction and to determine an appropriate course of action.”

The clinical hold is big setback for Oncothyreon, which has been on a roll the past year because of renewed enthusiasm for Stimuvax. The company renegotiated a partnership in December 2008 to shift all the development costs to Merck KGaA, while retaining a double-digit percentage royalty on sales if it becomes a marketed product. Then the big partner showed confidence in the program by starting a new 900-patient breast cancer study last June, followed by a 420-patient trial in December. Oncothyreon has also benefitted from renewed interest in treatments that stimulate the immune system to fight cancer, following the success of Seattle-based Dendreon’s treatment for prostate cancer.

While most investors are putting value on Oncothyreon for its stake in Stimuvax, it has other programs as well. The company has two cancer drugs in development, including one that is poised for mid-stage clinical trials this year, and a next-generation cancer vaccine in the works, which I discussed with Kirkman in a December interview.

Shares of Oncothyreon fell 27 percent to $3.49 at the close of trading today. Because so much of the company’s value is tied up in Stimuvax, there are going to be a lot of questions about this serious adverse event.

As is often the case with a report of a serious adverse event in a clinical trial, Oncothyreon’s conference call today raised more questions than it answered. Merck KGaA, along with the FDA … Next Page »

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If Seattle Genetics is destined to emerge a leading maker of antibody drugs that specifically target diseased cells, it will get there without the help of the world’s dominant player in the market for antibody drugs.

The Bothell, WA-based biotech company (NASDAQ: SGEN) said today that Roche’s U.S.-based Genentech unit has canceled a partnership the companies maintained for the past three years to co-develop dacetuzumab, an antibody for non-Hodgkin’s lymphoma and multiple myeloma. This means that Seattle Genetics will officially get back the full commercial rights to the treatment on June 8, six months after Roche served notice that it was ending the partnership.

The decision came after a portfolio review process at Roche, which has seen a lot of change this year. The Switzerland-based healthcare giant acquired South San Francisco-based Genentech, the world’s most valuable biotech company at the time, in March. Genentech is known as a biotech pioneer that developed or co-developed multi-billion dollar antibodies for cancer such as trastuzumab (Herceptin), rituximab (Rituxan), and bevacizumab (Avastin).

Genentech saw another opportunity in the antibody field when it struck a partnership with Seattle Genetics in January 2007. The bigger company agreed to pay Seattle Genetics $60 million upfront and potential milestone payments of $800 million over time for the right to co-develop daceutuzumab. One of the big ideas was to combine the new Seattle Genetics drug with Genentech’s rituximab. That was thought to be promising because the Seattle Genetics treatment was designed to hit a different target on cells, called CD-40, while the standard Genentech drug is made to block CD-20—and hitting two targets might be a more effective way to overcome resistance tumors eventually develop to treatment.

Seattle Genetics and its partner have seen mixed results with the new antibody this fall. Back in October, Seattle Genetics said it halted a clinical trial of dacetuzumab (formerly known as SGN-40) after an independent panel of safety monitors said mid-way through the study that it was unlikely to reach its goals. That was a big setback—the trial was set to enroll 224 patients with diffuse large B-cell lymphoma.

But this week, right before Genentech pulled the plug on the partnership, Seattle Genetics offered some new data that suggested dacetuzumab might not be toast. A study of 30 patients with diffuse large B-cell lymphoma, who got a different chemotherapy combination regimen than those in the other trial, found that half of the patients had their tumors partially or completely go away. Those new results were presented earlier this week at the American Society of Hematology meeting in New Orleans.

While losing a partner with the name cachet of Genentech is hard to spin around into a positive, Seattle Genetics CEO Clay Siegall did point out in a statement that dacetuzumab wasn’t really the company’s lead drug candidate anyway. That would be brentuximab vedotin, an “empowered antibody” that’s attached to a toxin to make it more potent against tumors. The empowered antibody is being tested in a pivotal clinical trial, and results are expected in the second half of 2010, the company has said. Seattle Genetics owns the full commercial rights to that product.

“We will evaluate available data as we consider possible next steps for the dacetuzumab program,” Siegall said in a statement. “We remain focused on advancing our lead product candidate, brentuximab vedotin.”

Seattle Genetics stock fell 5 percent at the opening bell this morning to $8.49 a share.

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When Deborah Dunsire, CEO of Millennium: The Takeda Oncology Company, talked about what makes the Boston area an attractive place to do business at a recent Xconomy Forum, she singled out the work of J. Wade Harper at Harvard Medical School. And after a little more follow up, I’ve found that Harper is helping Millennium discover its next generation of cancer drugs.

Cambridge, MA-based Millennium formalized a deal with Harper’s Harvard lab about two years ago to collaborate on research on how certain proteins regulate activities that are important to the survival and functions of cells. Joe Bolen, the company’s chief scientific officer, told me this week that the collaboration, which was first announced in January 2008, has been quite productive. Harper’s lab has identified proteins that could serve as new targets for cancer treatments, according to Bolen, and Millennium has developed chemical drugs to block those proteins. The company is in the process of validating the effectiveness of those drug candidates in animal studies.

There are many reasons for Millennium to take a strong interest in Harper’s lab. The crown jewel of the company’s cancer drug business is bortezomib (Velcade), a so-called proteasome inhibitor that blocks the function of proteins vital to the survival of cancer cells. Bortezomib, which is approved treating multiple myeloma and mantle cell lymphoma, reached blockbuster status in 2008 with more than $1.1 billion in sales. Yet Tokyo-based drug powerhouse Takeda Pharmaceutical bought Millennium in May 2008 for $8.8 billion not just because of its blockbuster drug, but also because of the biotech firm’s pipeline of treatments and internal expertise on cancer biology. (Luke provided an overview of Millennium’s drug pipeline earlier this year, and this week the firm announced that its first oral cancer drug has entered its initial clinical trial.)

While cancer patients won’t be able to benefit from the Millennium’s work with Harper’s lab for at least several years, the collaboration has become a model for how the company wants to work with top academics in the future, Bolen said. The collaboration is also important enough to be on Dunsire’s radar. “This has been so productive and useful on many, many levels this is absolutely the kind of relationship that we are looking for in the future,” Bolen says.

Millennium and Harper’s lab are in the midst of a three-year agreement, which gives the company a license to certain discoveries from the lab. (The financial terms of the agreement are … Next Page »

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A basic search of scientific literature says that Cambridge, MA-based Acceleron Pharma is trying to do something that won’t work. Past experiments suggest that a drug like its lead candidate is more likely to cause people to get anemia, not help treat it.

But Acceleron has witnessed the unexpected in small human studies, and it’s a big reason why this little company says its drug, ACE-011, has a shot to challenge the dominant player in the $11.5 billion worldwide anemia market, Thousand Oaks, CA-based Amgen (NASDAQ: AMGN).

“This has the opportunity to completely reverse the conventional wisdom in anemia,” says Steve Ertel, Acceleron’s vice president of corporate development. Adds CEO John Knopf: “Now there’s a lot of interest, but it was such an unexpected finding.”

Anemia is one of the first diseases that really benefitted from the biotech revolution, when Amgen created the first genetically engineered version of the erythopoeitin protein 20 years ago to stimulate the body to make more red blood cells. This business has become so big that Amgen lost $29 billion of stock market value in 2007 after its two anemia drugs were tied to a higher risk of heart attack, stroke, and death when used at high doses. Still, the drugs are considered critical tools in the modern treatment of patients with various states of kidney disease, and cancer patients who get anemia from chemotherapy.

Amgen’s drugs are injectable, and a number of competitors over the years have tried another route of treating anemia with oral pills that block enzymes, which is supposed to enable the body to regain its natural ability to produce red blood cells. San Francisco-based Fibrogen, GlaxoSmithKline, and San Diego-based Palkion are a few of the companies trying to develop drugs that interfere with these HIF prolyl hydroxylases.

Acceleron’s ACE-011 is completely different. It’s a genetically engineered protein that’s made to block a protein on cells known as the activin receptor type IIa. The main idea is that by hitting this target, the drug is supposed promote bone formation, which ought to be helpful for cancer patients who suffer from bone density loss. Past research has suggested it’s involved in red blood cell growth, so blocking it might cause people to become anemic, or so the thinking went, Knopf says.

What Acceleron found in its first clinical trial was that its drug appeared to improve bone formation like it was supposed to. But it had the opposite effect on red blood cells than would have been predicted. One single dose at the highest dose tested in the trial showed ACE-011 was basically like giving patients a transfusion with three full units of blood, without provoking any of the worrisome safety signals that the FDA has warned doctors about with high doses of the anemia drugs made by Amgen.

“No one really questions that it’s working,” Ertel says of the Acceleron drug.

Since anemia is such a big market, this says a lot about why Acceleron has been able to keep growing in the midst of a recession. The company announced back in May that it was expanding … Next Page »

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Cambridge, MA-based drug developer CombinatoRx (NASDAQ:CRXX) has licensed a compound from Clinical Data (NASDAQ:CLDA), of Newton, MA, to develop a combination treatment for multiple myeloma and other B-cell cancers, according to a press release. Clinical Data is eligible for up to $252 million in milestone fees from CombinatoRx and royalty payments on potential drug sales.

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[Correction appended---08/11/09]

Acetylon Pharmaceuticals is unveiling its technology today after closing a $7.25 million Series A round of financing to develop novel drugs to treat multiple myeloma and rheumatoid arthritis, according to the company. Many of the startup’s backers have close ties to the Dana-Farber Cancer Institute in Boston—including the company that owns the NFL’s New England Patriots, Acetylon president and CEO Walter Ogier tells Xconomy.

The biotech startup is researching drugs designed to block a specific enzyme involved in cancer and many other diseases, based on discoveries by scientists affiliated with Dana-Farber and Harvard University. The firm has drummed up investments from an interesting mix, including Acetylon co-founder and chairman Mark Cohen, a technology entrepreneur who serves on the board of Dana-Farber, and the Kraft Group, the Foxborough, MA, holding company founded by Patriots owner Robert Kraft, who is also a major supporter of Dana-Farber, according to Ogier.

Acetylon was formed last year to develop drugs that target one among a class of enzymes known as HDACs (short for histone deacetylases), which are involved in regulating the expression of certain genes in most types of cells. Interfering with these enzymes can interfere with gene expression, making them popular targets among pharma and biotech companies developing drugs to treat cancer and other diseases. In fact, the leading HDAC inhibitor drug on the market is Whitehouse Station, NJ-based drug giant Merck’s (NYSE:MRK) vorinostat (Zolinza) for treating the immune system cancer called lymphoma.

The problem with many HDAC inhibitors is that they can disrupt the function of healthy cells, causing side effects such as vomiting, fatigue, and even heart attacks, said Acetylon’s Ogier, who has joined the company as its first and only employee. Acetylon aims to avoid such side effects by developing drugs that home in on one specific enzyme known as HDAC6, as opposed to earlier drugs in this class that inhibit the function of many of the 18 known enzymes of this type.

“This is an interesting company because we have some new … Next Page »

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Cambridge, MA-based biotech Genzyme (NASDAQ:GENZ) reports that the firm has won European marketing approval for plerixafor (Mozobil) for injection in patients with two types of blood cancers—lymphoma and multiple myeloma—who need blood-forming stem cell transplants. The European Commission granted approval of plerixafor to be used in combination with granulocyte-colony stimulating factor (G-CSF) to boost the mobilization of stem cells in blood cancer patients, according to Genzyme. Plerixafor was cleared for sales in the U.S. last December.

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Genzyme won FDA approval today of a new drug for patients with blood cancers. The Cambridge, MA-based biotech company (NASDAQ: GENZ) said it has gotten clearance to sell plerixafor (Mozobil) as an injectable drug for patients with a pair of deadly blood malignancies, non-Hodgkin’s lymphoma and multiple myeloma, who need transplants of blood-forming stem cells.

The product is meant to be used to aid so-called “autologous” transplants—in which patients’ own cells are collected and stored for later transplantation—by helping to coax the blood-forming stem cells from the bone marrow into the bloodstream, where they can be collected. The new drug is approved for use in conjunction with a drug called granulocyte-colony stimulating factor (G-CSF), marketed by Amgen as pegfilgrastim (Neupogen). The combination of the Genzyme and Amgen drugs is supposed to boost the speed and efficiency of stem-cell collection over the Amgen drug alone.

“Mozobil is an important advancement in the treatment of patients with certain types of cancer who require a stem cell transplant,” said John F. DiPersio, a professor at Washington University in St. Louis, in a company statement. “This product should become an integral part of the treatment regimen for transplantation.”

The approval was expected by investors, according to Thomas Shrader, an analyst with Rodman & Renshaw in New York. The new Genzyme product should generate about $75 million in sales in 2009, its first full year on the market, Shrader said. Genzyme has applied for approval of the product in Europe, and expects approval in the second half of 2009, the company said. Genzyme acquired the drug through its purchase of Vancouver, BC-based AnorMed for $580 million in 2006.

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The American Society of Hematology (ASH) is one of those scientific meetings that usually flies below the radar of the wire services and big newspapers. Still, this year’s event in San Francisco has drawn more than 21,000 physicians, scientists, and intensely interested folks from biotech companies and Wall Street. They are all scouting new treatments for diseases of the blood, like leukemias, lymphomas, myelomas, and every clotting disorder you can shake a stick at.

If you don’t think this sounds like a big deal, check out the sales of anti-clotting drug clopidrogel (Plavix): $4.7 billion worldwide for Bristol-Myers Squibb and Sanofi-Aventis in 2007, even while they faced competition from cheaper generics. Then there’s old ASH standbys like Genentech and Biogen Idec’s rituximab (Rituxan) for non-Hodgkin’s lymphoma, which eclipsed $2 billion in U.S. sales last year and keeps growing.

So, I’ve been keeping an eye on the next big thing for the blood. Here are the newsiest stories we saw cross our biotechnology desk in our three-city network of Boston, San Diego, and Seattle:

Seattle Genetics

The Bothell, WA-based biotech company (NASDAQ: SGEN) caused a stir with its “empowered” antibody drug, which has the tumor-targeting ability of an antibody loaded with a potent toxin to give it extra tumor-killing kick. The drug, SGN-35, was able to completely wipe out aggressive forms of Hodgkin’s disease and related lymphomas with minimal side effects. In a study of 44 patients who were seriously ill and relapsed after a median of three prior rounds of chemotherapy, the Seattle Genetics drug caused tumors to completely disappear or mostly go away in more than one-third of patients (38 percent).

This data is promising enough that Seattle Genetics is preparing to go straight to pivotal studies for Hodgkin’s disease and anaplastic large cell lymphoma in early 2009, which could lead this drug to be FDA approved. Seattle Genetics CEO Clay Siegall said investigators at the ASH meeting are itching to participate in the pivotal studies. “There’s a lot of buzz here,” Siegall said during a break, when he called me yesterday. “The investigators are excited. We’ve never had this much excitement in the 10.5 year history of Seattle Genetics. The doctors really want to get involved in the trial.” He adds that there’s a backlog of patients who could enroll in the next studies, and he’s hopeful that they can be recruited to sign up quickly.

Millennium: The Takeda Oncology Company

Millennium Pharmaceuticals had a breakout performance at last year’s ASH. The Cambridge, MA-based biotech company, now the cancer division of Japan-based Takeda Pharmaceuticals, showed last year that bortezomib (Velcade) could cause complete remissions for 35 percent of patients with multiple myeloma on a combination treatment with its drug, compared with 5 percent who did that well on the combination alone. This year, it showed follow-up data from the trial, called Vista, that showed that early glimpse of promise is translating into an ability to help patients live longer.

Ligand Pharmaceuticals

This San Diego-based biotech company (NASDAQ: LGND) saw some positive data reported by its partner, GlaxoSmithKline. The drug giant reported … Next Page »

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Millennium Pharmaceuticals may not be the breakout performer at this year’s American Society of Hematology (ASH) meeting like it was a year ago, but another 12 months of follow-up data is strengthening the case that its cancer drug is no fluke.

Cambridge, MA-based Millennium, now a unit of Japan’s Takeda Pharmaceuticals, presented follow-up data today at the ASH conference in San Francisco, the largest annual meeting of specialists in blood cancers and other blood diseases. The results show bortezomib (Velcade) is able to extend lives for patients getting their initial round of therapy for multiple myeloma, a deadly cancer of the bone marrow. One study of 680 patients found that after more than two years of follow-up (25.9 months), patients had a 36 percent lower risk of death if they took a regimen with bortezomib than if they didn’t get the drug.

This data buttresses findings that Millennium released at last year’s ASH, when I saw a standing-room only crowd of physicians in Atlanta give the company a roaring standing ovation for the results it delivered for patients newly diagnosed with multiple myeloma. The drug, in combination with two immune suppressors, showed it was able to cause 35 percent of people newly diagnosed with multiple myeloma to go into complete remission. That was compared to just 5 percent who did that well on the immune suppressors alone. The trial of 680 patients, called Vista, cleared the way for Millennium to get expanded FDA clearance to market the drug to patients getting their first round of treatment, in addition to relapsers. It also no doubt helped propel it to blockbuster status this year with more than $1 billion in sales.

“Last year was an incredible landmark year for us in the first-line setting, and this year we are showing the important long-term effects,” says Nancy Simonian, Millennium’s chief medical officer.

Multiple myeloma may not be a household name, but the disease is fairly common as cancers go. About 20,000 cases are diagnosed each year in the U.S., and more than 10,000 people die from it, according to the American Cancer Society. That’s roughly on par with stomach cancer, and skin cancer.

One catch with all cancer drugs is that complete remissions can be a reliable predictor of a drug that helps extend lives, or they can be fleeting, as tumors bounce right back and kill people. So the follow-up data is important. This question will take years to answer, because patients with this prognosis currently can expect to live five to six years, so it will take more time … Next Page »

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