Seattle Genetics is getting some new warnings, including one new language about a potentially deadly brain infection, put into the FDA-approved prescribing information of its lone marketed product.

The company (NASDAQ: SGEN) said today it is working on an update to the label for brentuximab vedotin (Adcetris), which will include a boxed warning about the risk of patients on the lymphoma drug getting a potentially fatal brain infection called progressive multifocal leukoencephalopathy (PML). Seattle Genetics’ original drug label, cleared by the FDA in August, said there had been a case of PML in clinical trials, but now that the drug has been used more widely on the market, Seattle Genetics discovered a second case last fall, and said today it has learned of a suspected third case of PML. That information is prompting new warning language that’s supposed to help doctors spot signs of PML.

Several new biotech drugs have been linked to cases of PML, including Roche and Biogen Idec’s hit lymphoma drug rituximab (Rituxan). The Seattle Genetics drug is designed to hit a different target on cancer cells, and it is approved for use in a couple of rare malignancies—Hodgkin’s disease and anaplastic large cell lymphoma. The new treatment has shown strong ability to shrink tumors in clinical trials in the majority of patients who have essentially run out of options, and it has beaten Wall Street’s initial sales expectations. Now Seattle Genetics is looking to expand use of the drug to larger groups of patients. One of those label-expansion studies showed that the new drug shouldn’t be used in combination with a chemotherapy agent known as bleomycin, because of an elevated rate of lung toxicity, so a warning about that is also being incorporated into the Adcetris label.

The bleomycin warning isn’t much of a concern, because even though it’s part of a typical chemo regimen, Adcetris was never approved to be used in combination with that drug, and researchers are hopeful that Adcetris might be able to replace bleomycin for use in some patients, because the new drug has a milder side effect profile when used on its own.

“Our first priority is patient safety. By developing these agreed upon label updates with the FDA regarding PML and the contraindication with bleomycin, we aim to heighten awareness among healthcare professionals in order to most safely treat their patients with Adcetris. Although PML in lymphoma patients can be caused by factors such as underlying disease and prior therapies that affect the immune system, a contributory role of Adcetris cannot be excluded,” said Tom Reynolds, the chief medical officer of Seattle Genetics, in a statement.

Previous studies have said patients with blood cancers have about a 0.07 percent chance (1 in 1,400) of getting PML. Seattle Genetics didn’t say what the ratio is for patients getting Adcetris, but it has had two confirmed cases, and one suspected case, out of more than 2,000 patients worldwide who have gotten the new drug.

Shares of Seattle Genetics fell about 6.3 percent to $17.28 at 10:14 am Eastern time.

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Seattle Genetics has had a bit of a dust-up today in the stock market, as investors have been seeking to make sense of a second case of a dangerous adverse event seen in a patient on the company’s new lymphoma drug.

Shares of the company (NASDAQ: SGEN) dipped almost 6 percent early in the day, after Wall Street analyst Elliot Favus circulated a report about how a second case of progressive multifocal leukoencephalopathy (PML) has been diagnosed in a patient taking the company’s flagship lymphoma drug. Favus, known for his bearish positions, didn’t immediately respond to a request for a copy of his report.

Seattle Genetics stock regained much of its value as the day went on, but news on PML is bound to rattle nerves on Wall Street. That’s because this condition is a rare, and sometimes deadly, brain infection that patients sometimes get when taking modern targeted biologic drugs like Biogen Idec’s natalizumab (Tysabri), and Roche/Genentech’s rituximab (Rituxan). The Tysabri case in particular made headlines, and prompted that drug to be temporarily withdrawn from the market, until scientists better understood the risks and benefits. Since Seattle Genetics’ brentuximab vedotin (Adcetris) only arrived on the market in August, and Seattle Genetics depends heavily on it as its only marketed product, it’s understandable why investors got jumpy.

The Seattle Genetics drug, for patients with Hodgkin’s lymphoma and anaplastic large cell lymphoma, has shown impressive effectiveness in clinical trials. It provided significant tumor shrinkage in 75 percent of patients with relapsed forms of Hodgkin’s disease in a clinical trial, and in about 86 percent of patients with anaplastic large-cell lymphoma. Researchers are still following patients to see how long those responses really do last, and to what extent they may help people live longer. The most common side effects found in clinical trials were a depletion in infection-fighting white blood cells, nerve damage in the fingers and toes, fatigue, nausea, and anemia.

Clay Siegall

CEO Clay Siegall offered a spirited defense of his product today when I reached him by phone. The PML association with Adcetris isn’t new, he said, as the first page of the product’s FDA approved prescribing information includes a warning about the condition. The warning says that a patient in clinical trials, who had received four prior chemotherapy regimens before getting Adcetris, died from PML.

Siegall did confirm that a more recent, second case of PML in an Adcetris patient has been diagnosed. That case was reported to the company, which shared with the information with the FDA. He wouldn’t comment on the patient’s condition, saying that it is company policy not to talk about individual patients.

To provide some context, Siegall notes that PML is part of the underlying disease that some patients have with lymphomas. In some cases, patients get multiple rounds of chemotherapy, which suppresses their immune systems, and makes them more vulnerable to … Next Page »

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ImmunoGen, in the eyes of Wall Street, is largely defined by one thing—its relationship with industry giant Genentech. That’s because Genentech uses ImmunoGen’s technology to help amp up the antibody trastuzumab (Herceptin) into a more potent breast cancer drug called T-DM1, which has shown significant promise in clinical trials.

Yet ImmunoGen chief executive Daniel Junius says there’s a lot more to the story. Today, his firm is hosting an analyst day in New York to emphasize some of the drugs that are wholly-owned by ImmunoGen—unlike T-DM1, in which Genentech will reap the lion’s share of the rewards. Junius gave me a preview yesterday of two so-called antibody-drug conjugates—which link targeted antibodies with toxins to make them more potent—that are 100-percent owned by ImmunoGen. Though these two molecules haven’t begun human testing, Junius made a good case for why they are important to his company and why they could prove valuable for the treatment of certain types of cancer.

Junius, who became CEO of ImmunoGen in 2009, wants his company to expand its own internal pipeline of compounds along with continuing its partnerships in which it shares rights to other products with drug giants such as Genentech (a unit of Swiss healthcare firm Roche) and Sanofi-Aventis. “We’re working very hard to be moving from a partner-based company—although that will still have a role—to being one that is much more focused on proprietary compounds,” he says.

This thinking makes sense given the impact of a recent regulatory setback for Genentech’s T-DM1 on ImmunoGen. The FDA handed Roche/Genentech a “refusal to file” letter in late August, essentially saying it wouldn’t accept the firm’s application for accelerated marketing approval of T-DM1 as a breast cancer treatment because of the agency’s opinion that the experimental treatment did not quality at this time for that faster-than-usual type of review. Some investors immediately fled from ImmunoGen’s stock, sending its shares down more than 35 percent on August 27, the day that Roche announced the “refuse to file” letter.

ImmunoGen’s stock has since recovered the value it lost on the day of the FDA letter, and Roche is still advancing T-DM1 through the third and final stage of clinical trials normally required for FDA approval. ImmunoGen also announced a partnership deal in October with Novartis that brought the firm $45 million in upfront cash and the opportunity for additional payments related to specific compounds within the collaboration. (ImmunoGen’s stock closed at $8.80 per share on Thursday, giving the company a market value of $598.7 million.)

The two compounds that the company plans to highlight today are called IMGN859 and IMGN529. Like T-DM1, these compounds combine the ability of antibodies to home in on tumor targets with the killer punch of an anti-cancer toxin. The firm uses linkers to keep the toxins bound to the antibody while it is in the bloodstream, limiting exposure to the anti-cancer agent on healthy tissues. ImmunoGen is reserving some of the details on its latest two compounds until a scientific meeting later this year.

Junius says that the compound called IMGN529 features an antibody with an affinity for an undisclosed target on non-Hodgkin’s lymphomas, a cancer of the white blood cells. In fact, the firm’s antibody alone—without any extra kick from an attached toxin—compared favorably in models of non-Hodgkin’s lymphoma with available antibody drugs such as Biogen Idec (NASDAQ:BIIB) and Genentech’s lucrative … Next Page »

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Calistoga Pharmaceuticals has been stirring up buzz at medical meetings for more than a year about how its experimental treatment is shrinking tumors for patients with certain blood cancers that resist other therapies. And today the Seattle-based company is showing still more evidence that strengthens the medical case for its drug, as the tumor shrinkage effect appears to be long-lasting, and the drug looks like it can be safely combined with other standard meds.

The latest data about Calistoga’s experimental drug, CAL-101, is being presented today at the American Society of Hematology meeting in Orlando, FL. The main study has been expanded over time to include 177 patients, and has been adjusted since it started in June 2008 to now focus primarily where it appears to be most effective: patients with chronic lymphocytic leukemia and slow-growing or “indolent” non-Hodgkin’s lymphoma. Even after patients saw their disease worsen following multiple rounds of treatment, the Calistoga drug kept their tumors from spreading for more than a year, researchers said. And an early look at a second study of the Calistoga therapy said it didn’t appear to add any extra side effects when combined with standard drugs like Cephalon’s bendamustine (Treanda) or Roche and Biogen Idec’s rituximab (Rituxan).

“As we’ve added more and more numbers of patients, you can see it’s not a statistical fluke,” says Carol Gallagher, Calistoga’s CEO. “The response rates we are seeing are real, and so is the duration of response.”

Calistoga, which raised its first sizable venture round in 2007, has been emerging for some time now as one of the top private biotech companies in Seattle. The company has attracted another $70 million in venture capital over the past 18 months to drive the development of this drug, which is seeking to attack cancer through a hot avenue known as the PI3 kinase pathway. Scientists are excited about this pathway because it is thought to control critical cell processes like proliferation, migration, and cell survival. When these normal functions get flipped into an overactive mode, it’s a hallmark of cancer cells growing out of control.

Carol Gallagher

Pharma heavyweights like GlaxoSmithKline, Novartis, and Sanofi-Aventis are pursuing this strategy, yet Calistoga is seeking to differentiate itself by aiming for more specific types of PI3 kinase, particularly one known as the delta isoform. By being more specific, it hopes to be more potent against particular blood cancers that overexpress the delta isoform, and minimize side effects.

Calistoga’s first study enrolled a wide variety of patients with blood cancers. More than half of them had relapsed or didn’t respond any more to existing therapies. Without receiving any other combination treatments, people in the study took CAL-101, a twice-daily oral pill, for a 28-day course of therapy, for as many as 12 cycles. Researchers enrolled patients with five different kinds of malignancies in this study, looking for signs in which CAL-101 showed the most promise.

The strongest evidence over time appears to be for two forms of blood cancers—chronic lymphocytic leukemia, and slow-growing “indolent” non-Hodgkin’s lymphoma.

First, here’s what is known about chronic lymphocytic leukemia. There were 54 patients … Next Page »

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Seattle Genetics is reporting today on a batch of clinical trial results that represent a watershed moment for the company, its technology for creating “empowered antibodies” against cancer, and which could provide a new source of hope for patients with Hodgkin’s disease.

The company (NASDAQ: SGEN) and its partner, Cambridge, MA-based Millennium: The Takeda Oncology Company, are presenting detailed results today from a study of 102 patients who got brentuximab vedotin (SGN-35) as a treatment for relapsed forms of Hodgkin’s disease. Researchers found that one-third of the patients (34 percent) had their tumors completely eliminated after getting the new drug, while another 41 percent had their tumors shrink by half or more, and a total of 94 percent had at least some observable tumor shrinkage. All kinds of nitty gritty details on how long the remissions lasted, and the drug’s side effect profile, are being disclosed today at the American Society of Hematology (ASH) meeting in Orlando, FL.

Seattle Genetics plans to package this data in an application to the FDA by the end of March, in which it will seek clearance to start selling the product in the U.S., where it holds 100 percent of the commercial rights. Millennium, which has a lot of experience in blood cancers with its $1 billion hit bortezomib (Velcade), holds the rights to this drug in Europe and plans to seek regulatory clearance there in 2011. If the FDA allows the drug on the market next year, it will mean Seattle Genetics will be transformed from an R&D-only operation into a more diversified commercial organization. The drug is also being closely watched in the biotech industry, because it could be the first time anyone has been successful with an “empowered antibody”—a molecule that’s designed to zero in specifically on cancerous cells, carrying a potent tumor-killing toxin.

While about two-thirds of the 8,500 patients diagnosed in the U.S. with Hodgkin’s disease are successfully treated with chemotherapy, one-third eventually get relapsed, treatment-resistant forms that provide a grim prognosis—a life expectancy of just two to three years. The new Seattle Genetics drug could be the first treatment for this patient population in more than two decades. Seattle Genetics already released some of the results to investors in September, and its stock has soared 56 percent this year on the news, but this is the first time the data will get scrutinized in detail at a medical meeting with more than 20,000 people in attendance.

Clay Siegall

“I’ve been a part of many clinical trials before, and this is one of the best results I’ve ever seen,” says Robert Chen, a hematologist at the City of Hope in Duarte, CA, and an investigator on the study who will present to his peers at the ASH conference. “I’m very excited for patients with Hodgkin’s disease.”

Clay Siegall, the CEO who co-founded Seattle Genetics a dozen years ago, says he sees the new drug as a cornerstone in a plan for the company to become a much bigger force than it is today in cancer drug R&D. “We want to be the next Celgene, the next Genzyme, the next really important biotech company,” Siegall says. “We have the nucleus, and we have the technology to do it.”

Before going deep into the clinical trial results, a little science … Next Page »

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[Update: 4:15 pm Pacific] One of the key people at Dendreon (NASDAQ: DNDN) who was hired to make its new prostate cancer drug a success is out of a job after less than a year.

Seattle-based Dendreon said today in a regulatory filing that Varun Nanda has left the company effective immediately. Nanda, Dendreon’s senior vice president of global commercial operations, will get severance benefits in accordance with his employment agreement, the company said. No reason was given for the departure in the regulatory filing.

Nanda’s hiring was announced in April, just a couple weeks before Dendreon won FDA approval to start selling sipuleucel-T (Provenge) a first-of-its-kind immune boosting therapy for prostate cancer. Nanda was previously the senior vice president and head of global oncology for Roche, the world’s largest maker of cancer drugs, which sells billion-dollar hits like rituximab (Rituxan), bevacizumab (Avastin), and trastuzumab (Herceptin). That’s about as high-profile as it gets in the cancer drug business, and Dendreon heralded the arrival of Nanda as a coup.

“With more than twenty years of commercial experience, Varun will help guide our team as we move closer to realizing our mission of transforming the lives of cancer patients,”  Dendreon’s chief operating officer, Hans Bishop, said in a statement on April 8. “Varun’s depth of experience launching Avastin and leading several breakthrough global oncology products will be highly relevant to our transformation from a purely R&D organization into a world-class commercial organization.”

While the drugs from Roche are targeted antibodies that are delivered via liquids in a vial, Dendreon’s treatment requires a more complicated process in which blood is withdrawn, exposed to markers found on prostate cancer cells, and then re-infused so that the patient’s immune system knows how to better fight the malignancy. In its first year on the market, Dendreon’s manufacturing system has been unable to keep up with demand from patients. The company is operating at maximum now at about $9 to $10 million in sales per month. When more factory capacity comes online later in 2011, the company expects to be able to sell $350 million to $400 million of the treatment. Eventually, many analysts predict it will reach billion-dollar annual blockbuster status.

[Update] Dendreon spokeswoman Katherine Stueland wrote back with a short comment that didn’t say why Nanda left the company. She did say that Bishop, Dendreon’s chief operating officer, will oversee marketing and sales until it identifies a replacement for Nanda.

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Roche made big news in the pharmaceutical business today when it said it is cutting 4,800 jobs as part of a major restructuring plan. And, no surprise, hundreds of those job cuts are coming from its biggest U.S. asset, South San Francisco-based Genentech.

About 350 to 450 people in Genentech’s manufacturing group in South San Francisco will lose their jobs, in addition to 100 at the company’s manufacturing plants in Vacaville, CA, and another 90 people in Oceanside, CA, according to Genentech spokeswoman Robin Snyder. An additional 200 positions from other departments throughout Genentech are being eliminated, although some of those cost savings will come through choosing not to fill open positions, Snyder says.

Taken together, this could represent about 840 jobs that will be wiped out. Genentech, the biotech industry trailblazer founded in 1976, currently has about 13,000 employees companywide. About 8,800 of these people work at the company’s flagship campus in South San Francisco, Snyder says. She added that none of the cuts will be made among Genentech’s scientific staff, or in early drug development. The cuts that are being made will occur between now and the end of 2012, Snyder says.

When asked what the cuts say about Roche’s commitment to Genentech’s operations in Northern California, Snyder said “Genentech is the biggest site in the entire organization. It is very committed to Genentech.”

The handwriting has essentially been on the wall for a lot of the manufacturing operations in South San Francisco. As far back as 2006, Genentech said it was planning to shift the manufacturing group on campus away from commercial output, and gear it more toward producing batches for use in clinical trials, Snyder says.

Roche has held a majority ownership stake in Genentech since 1990, but it allowed the biotech pioneer to operate essentially as an independent company until it paid $46.8 billion to acquire the whole company in March 2009. At the time the deal closed, Roche said it wanted to preserve the Genentech’s legendary culture of creativity and independence.

One of the bigger surprises in the Roche news was that the company is dropping it efforts to discover new treatments that use RNA interference technology. This is supposed to represent a new paradigm of gene-silencing technology that reaches targets inaccessible by traditional antibody and protein drugs like those made by Genentech, or conventional small molecule pills that Roche and other pharma giants sell.

This revelation had a negative impact on a couple of leaders in the RNAi field—Cambridge, MA-based Alnylam Pharmaceuticals (NASDAQ: ALNY), and Vancouver, BC-based Tekmira Pharmaceuticals (NASDAQ: TKMR). One way to interpret the news would be to say that Roche has more confidence in the future of protein drugs like Genentech’s blockbusters trastuzumab (Herceptin), bevacizumab (Avastin), and rituximab (Rituxan), compared to the outlook it sees for RNAi drugs—none of which have earned FDA approval as of yet. Another way to look at it would be that this creates an opening for smaller competitors. Either way, it will be interesting to see which projects get green-lighted at the new, leaner Roche R&D machine.

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There was good news and bad news in the Boston life sciences scene this past week. Some companies announced layoffs and restructuring, while others attracted funding and won regulatory approval.

—Sunovion Pharmaceuticals of Marlborough, MA, nabbed FDA approval for Latuda (lurasidone HCl), its once-daily, oral tablet for treating schizophrenia. The drug is expected to hit the market in early 2011.

—Boston-area Energesis Pharmaceuticals is looking for ways to tap into brown fat cells, which are found in humans and animals and thought to boost human metabolic function, for developing drugs that fight obesity. The startup recently won $50,000 from the business competition MassChallenge, and is seeking funding to amp up its drug discovery efforts.

—Major restructuring news came from Weston, MA-headquartered Biogen Idec (NASDAQ: BIIB), the world’s top maker of multiple sclerosis drugs. The drug developer’s plans include laying off most of the workers at its San Diego facility, consolidating its Waltham, MA, and Wellesley, MA, sites in Weston and Cambridge, MA, rearranging the management layers, and leaving sales and marketing efforts for its blockbuster drug rituximab (Rituxan) to its partner Genentech. All told, about 650 positions will be cut, about 300 of which will come at the San Diego site. Biogen CEO George Scangos is looking to shape the company into something more like a biotech, rather than a pharma giant, and remove its interest in cancer and cardiosvascular drugs to focus more closely on the field of neurology, Ryan wrote in a follow-up piece.

—Karyopharm Therapeutics, a Newton, MA-based biotech focusing on treatments for cancer, autoimmune disease, and HIV, announced it had brought in $20 million in Series A money. The startup, founded in 2009, plans to put the money towards developing its technology, which is designed to flag major tumor suppressor and growth regulatory proteins to kill cancer cells while sparing healthy cells, for a clinical trial against an unspecified cancer target.

—In more layoff news, Cambridge-based Acceleron Pharma revealed that it was shrinking its workforce by about 40 percent, or 57 positions, according to a report in the Boston Globe. The staff cuts came after a recently announced partnership with U.K.-based Shire. Acceleron trimmed jobs across all of its disciplines, in order to keep its edge in manufacturing, discovery research, protein engineering, and clinical development.

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Biogen Idec CEO George Scangos is putting his stamp on the direction of the company, by making some bold moves to cut jobs, facilities, and drug development programs. It’s all part of a bid to make a bigger impact in one area—neurology.

Weston, MA-based Biogen Idec (NASDAQ: BIIB), the world’s largest maker of multiple sclerosis drugs, outlined a sweeping series of cutbacks and strategic moves in a statement this morning. The changes are designed to save the company $300 million a year, the company said.

—Biogen is cutting 13 percent of its workforce. About 650 people will lose their jobs, leaving the company with a staff of about 4,275 employees worldwide.

—The company is going to close down its San Diego site, and its eastern Massachusetts sites in Waltham, MA and Wellesley, MA will be consolidated in Cambridge, MA and Weston, MA. This is a big blow to the San Diego community, which has been a part of the company since the 2003 merger between Biogen and Idec Pharmaceuticals. “The closing of our San Diego site is especially painful, as it is the home of the original Idec Pharmaceuticals and has played a fundamental role in the success of the company,” Scangos said in a statement.

—Cardiovascular disease R&D is being axed, and Biogen Idec will look to spin out or outlicense its cancer drug portfolio. The company plans to concentrate in the future on neurology treatments like its top-selling drugs for MS, and its expertise in the development of what it calls “select, high-impact biological therapies” which have the potential to truly stand out in the market. A total of 11 drug development programs are being cut. “We are a mile wide and an inch deep,” Scangos said in a conference call. “We need to focus.”

—Big changes are coming to the organizational chart. Business development, venture development, and corporate strategy are being reorganized “to improve crispness and timeliness of decision making and execution.” Layers of management will be eliminated, cutting back on bureaucracy. The company said it is now looking for a new head of its combined corporate development group.

George Scangos

—Biogen Idec is getting rid of the sales force that pitches the blockbuster drug rituximab (Rituxan) for cancer and rheumatoid arthritis. Biogen’s partner, the Roche unit of Genentech, will be responsible for the U.S. sales and marketing of Rituxan.

Scangos, a scientist and former CEO of South San Francisco-based Exelixis (NASDAQ: EXEL), said that R&D at Biogen Idec had to improve from the minute he was publicly introduced as the new boss last June. The company has been repeatedly hit with critiques from billionaire activist Carl Icahn, who has complained about the company’s lack of R&D productivity, noting that the company hasn’t brought a product to market since the 2004 introduction of its MS therapy natalizumab (Tysabri).

Four months after taking the job, Scangos had this to say: “Biogen Idec will be better off as a result of these actions. First, we will have increased focus. We have been operating in too many therapeutic areas and haven’t maximized … Next Page »

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It was a busy New England area life sciences news week, with headlines of drug collaborations, failed applications with the FDA, clinical trial results, plus some lengthier profile stories.

—Providence, RI-based Shape Up The Nation is using social networking to invite people’s friends to encourage them to eat better and make healthier choices, Ryan wrote. The four-year-old startup raised $5 million earlier this year from Excel Venture Management and Cue Ball Group, landed CVS Caremark (NYSE: CVS) as its first big customer, and is adding other Fortune 500 companies to the list.

—The diabetes drug developed in a collaboration by San Diego-based Amylin Pharmaceuticals (NASDAQ: AMLN), Waltham, MA-based Alkermes (NASDAQ: ALKS), and drug giant Eli Lilly (NYSE: LLY) failed to garner FDA approval, the companies announced on Tuesday. The regulatory agency is requiring a new study looking at whether the drug—the once-weekly injectable version of exenatide (Bydureon)—is connected to irregular heartbeat in trial patients. The application for FDA approval of the drug was delayed earlier this year, due to manufacturing questions and the agency’s request for a risk mitigation strategy of the drug. By Wednesday morning Amylin’s and Alkermes’ share prices had fallen 50 percent and 29 percent, respectively. Lilly, with a more diversified drug pipeline, saw its shares drop by about 5 percent.

—Cubist Pharmaceuticals (NASDAQ: CBST), a Lexington, MA-based maker of acute care drugs, announced it had priced a $400 million offering of convertible notes, which have an annual interest rate of 2.5 percent and mature on November 1, 2017. The deal underwriters have the option to purchase $50 million in additional notes. Cubist will put the proceeds toward repurchasing about $191 million in notes that carry a 2.25 annual interest rate and are due June 15, 2013, as well as its investing in its pipeline products, corporate expenses, and acquisitions.

—Cambridge-based Genzyme (NASDAQ: GENZ) reported data from a late-stage clinical trial comparing its drug clofarabine (Clolar) in combination with chemotherpy to treatment with chemotherapy and a placebo. Those treated with the drug did not live longer than those only given the placebo, but the clofarabine group saw its remission rate double, to 47 percent, Genzyme said. The firm will … Next Page »

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Weston, MA-based Biogen Idec (NASDAQ: BIIB) and South San Francisco-based Genentech said today they are restructuring an alliance to co-develop new antibodies against CD20, the same cellular target of the hit cancer drug rituximab (Rituxan). Under the amended partnership, Genentech will pay the full costs of developing ocrelizumab for multiple sclerosis, and keep most of the profits while Biogen Idec will get royalties roughly equal to its current 30 percent interest in the drug. Biogen Idec has also agreed to pay $10 million to Genentech, and increase its share of development costs from 30 percent to 35 percent for the development of GA-101, another anti-CD20 antibody in development for chronic lymphocytic leukemia and non-Hodgkin’s lymphoma. Once GA-101 hits certain sales targets, then Biogen Idec’s share of profits from Rituxan will drop from 4o percent to 35 percent, the companies said.

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Calistoga Pharmaceuticals, the Seattle-based developer of cancer drugs, said today it has started a mid-stage clinical trial of its lead drug candidate for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma. The trial is expected to enroll 65 patients who will get a twice-daily dose of Calistoga’s CAL-101 oral pill in combination with eight weekly infusions of Roche and Biogen Idec’s rituximab (Rituxan). Patients won’t get standard chemotherapy, and they will stay on CAL-101 as long as they continue to benefit. Calistoga raised $40 million in venture capital in June after it revealed promising results from its first clinical trial of CAL-101 at a medical meeting.

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Seattle Genetics is making history today, after a dozen years of effort, with groundbreaking clinical trial results in the field of cancer drugs. The results pave the way for the first successful “empowered antibody” drug for cancer, and a new therapy for people who have run out of options for fighting Hodgkin’s disease.

The Bothell, WA-based company (NASDAQ: SGEN) and its Cambridge, MA-based partner, Millennium: The Takeda Oncology Company, are reporting today that Seattle Genetics’ lead drug candidate, brentuximab vedotin, was able to partially or completely shrink tumors for 75 percent of the 102 patients with Hodgkin’s disease who enrolled in a pivotal clinical trial. Most cancer drugs shrink tumors in fewer than 30 percent of patients. That means Seattle Genetics unequivocally surpassed the usual definition of success, and is now in a position to seek FDA approval to market the drug in the U.S.

“I’ve been doing cancer research and making cancer drugs for 25 years, and these are the kind of data you dream of,” says Clay Siegall, the co-founder and CEO of Seattle Genetics. “We are going to have an amazing impact on patients.”

Even though the patients were the sickest of the sick, their tumors were kept in check for at least six months. Doctors will continue to follow the patients to see how long the tumors remain stable, and ultimately how long the drug helps the patients live. Detailed results from the study will be presented at an upcoming medical meeting.

Armed with this new batch of results, Seattle Genetics now plans to seek FDA clearance in the first half of 2011, and to ask for a faster-than-usual six-month regulatory review that is sometimes granted for lifesaving therapies.

Clay Siegall

The results are important for several reasons. If the FDA gives the green light, brentuximab vedotin (formerly known as SGN-35) will become a transformative asset for Seattle Genetics, as the company will morph from an R&D-only operation into a more fully integrated company that discovers, develops, and sells pharmaceuticals. Scientifically, the drug is potentially the first of a new class of drugs designed to zero in specifically on cancerous cells, with a potent toxin to give them extra tumor-killing punch. Medically, the drug could offer a new option for many of the 8,500 patients in the U.S. diagnosed with Hodgkin’s each year, as well as other patients with lymphomas that overexpress a protein marker called CD30, which brentuximab is designed to hit.

Millennium, which last year paid Seattle Genetics $60 million upfront to obtain rights to the product outside North America, said its next move will be … Next Page »

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The people at Genentech have created an enduring perception about antibodies, which says these Y-shaped protein drugs are really good at specifically targeting cancer cells. When I was at Bloomberg News a few years ago, I learned that investors paid close attention to multi-billion dollar sales trends of the big three antibody drugs for cancer—bevacizumab (Avastin), trastuzumab (Herceptin), and rituximab (Rituxan)—and not much else at biotech’s standard-bearing company.

But as any antibody drug developer will tell you, antibodies can be used for a lot more than just targeting cancer cells. Just down the hill from Antibodies ‘R Us in South San Francisco is KaloBios, a venture-backed company with a vision of making antibodies that can specifically interfere with a deadly bacterium found in the lungs of people with cystic fibrosis, and in patients on ventilators who get infections while they’re in hospital intensive care units.

KaloBios, which draws its name from the Greek expression for “good life,” is hot on the trail of an antibody drug for pseudomonas bacterial infections. The company, founded in 2002, has settled on this direction with its lead compound after raising four rounds of venture capital worth a combined $80 million. This 50-person company has a lot of interested parties watching how it does—with a roster of backers that includes MPM Capital, Sofinnova Ventures, Alloy Ventures, GBS Venture Partners, Mitsubishi UFJ Capital, Genzyme Ventures, Baxter International, and the Development Bank of Japan. If KaloBios plays its card right, CEO David Pritchard says, it should be able to build a business worth more than $1 billion within the next three to four years.

“There aren’t very many good names left out there in antibodies that haven’t already been acquired,” Pritchard says.

David Pritchard

The antibody drug market was expected to generate $30 billion in worldwide sales in 2009, with an annual growth rate of 14 percent through 2012, according to Datamonitor. Some of the biggest drugs in this category have led to some of biotech’s biggest takeovers of recent years—like Roche’s purchase of Genentech, Eli Lilly’s takeover of ImClone Systems, AstraZeneca’s deal for MedImmune, Amgen’s buy of Abgenix, and Bristol-Myers Squibb’s acquisition of Medarex.

KaloBios sees itself following the industry trend over time, gradually building value to become more like the remaining top-tier antibody companies that are still independent—Cheshire, CT-based Alexion Pharmaceuticals (NASDAQ: ALXN), Tarrytown, NY-based Regeneron Pharmaceuticals (NASDAQ: REGN), and Seattle Genetics (NASDAQ: SGEN).

What KaloBios has that’s different is a platform technology for making antibodies, as well as some different ideas on how to apply them for medicine. The main scientific idea is to pump out antibody candidates with what it calls “Humaneering” technology. The technology is supposed to make antibodies that are super-specifically focused on the target and nothing else; bind tightly with the target on the cell of interest and don’t let go; and avoid provoking an immune system reaction that essentially can render the drug useless. KaloBios, to be sure, isn’t the only company out there … Next Page »

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Lebanon, NH-based biotech startup Adimab has grown the ranks of its Big Pharma collaborators, which are coveted for their deep pockets and other resources they bring to smaller firms. Swiss drug giant Novartis has inked a research agreement with Adimab to access the startup’s synthetic immune system of sorts that churns out potential antibody drugs.

Adimab has announced research deals with four of the largest drugmakers in the world— Merck & Co., Roche, Pfizer, and now Novartis—since June 2009. It’s also collaborated with one undisclosed firm. The payments these companies have made to Adimab made the three-year old startup cash flow positive for the first time during the April, May, and June quarter of this year, says company co-founder and CEO Tillman Gerngross, and he expects the company to be profitable for the year.

The financial terms of Adimab’s deal with Novartis aren’t being disclosed. The agreement is for Adimab to use its technology to discover antibodies that could be drugs against two undisclosed disease targets of Novartis’s choosing. Merck has also made its second milestone payment to Adimab in their collaboration.

Novartis has decided to give Adimab’s technology a try despite the fact that the drug behemoth in 2007 struck a potential $1 billion-plus deal with Germany-based MorphoSys to gain broad access to that biotech’s method for discovering antibody drugs. To Gerngross, Novartis’s willingness to give his firm’s technology a shot provides extra validation of its potential to vastly streamline the process of discovering antibodies. Which could shrink the time it takes drug companies to identify antibodies that have the potential to be valuable and life-saving drugs for cancer, inflammatory diseases, neurological disorders, and other illnesses.

“What you’re seeing in the antibody discovery space is that [companies] that thought they had everything and already made very substantial financial commitments in that area still see something in our platform that has made them … Next Page »

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Scientists have been dreaming for decades about drugs that go after cancer cells like heat-seeking missiles. The idea is to destroy the enemy and spare other cells from the collateral damage that so many cancer drugs cause. Now after more than 10 years of sustained effort by one of largest teams ever assembled at Genentech, and some gut-wrenching ups and downs, that vision is on the verge of turning into reality.

This story began when Genentech, the South San Francisco biotech pioneer now owned by Roche, made history back in September 1998. That’s when it got the green light from the FDA to sell a genetically engineered antibody designed to seek out a mutated protein found on malignant cells in about one-fourth of women with breast cancer. The drug, trastuzumab (marketed as Herceptin), has been proven over the years to work even better than Genentech first imagined it would in women with early stages of cancer. The therapy is now one of the biggest selling biotech products in history, generating more than $5 billion in annual worldwide sales.

Yet from the moment of the FDA’s approval, a small group of scientists in-house were thinking even bigger. They suspected that their engineered antibody, even though it could hit a specific target on cells, would fail to land a real knockout punch against tumors. The scientists had shown that drugs of trastuzumab’s generation could interrupt signals cancer cells need to grow, and they later realized that the drugs could also sometimes provoke an immune system reaction against the tumor. But they weren’t a cure.

Mark Sliwkowski

So scientists at Genentech, including Mark Sliwkowski, wondered if a targeted antibody would work even better if they could attach potent little toxins to it, making it into a “smart bomb” or an “empowered antibody.” Nobody has turned this concept into a commercial success after 30 years of trying, but Genentech and its partner in Waltham, MA, ImmunoGen (NASDAQ: IMGN), are betting they have finally been able to pull off this daunting scientific trick.

Evidence to support the claim arrived last December at the San Antonio Breast Cancer Symposium. A next-generation form of Herceptin, jointly developed by Genentech and ImmunoGen, called T-DM1, partially or completely shrank tumors in about one-third of 110 patients who were extremely sick, whose cancer was still worsening after they had endured an average of seven prior rounds of therapy. The most common severe adverse event was a depletion of blood platelet cells, which was found in 5.5 percent of patients, researchers said. The balance of safety and effectiveness was so convincing that Genentech plans to seek FDA approval before the end of this year to start selling T-DM1 in the U.S.

Important as it may be for breast cancer patients, the finding has re-energized the once moribund field of antibody-drug combinations, often called “antibody drug conjugates.” Genentech is so bullish on the concept that it now has 50 such drug candidates moving through its internal R&D pipeline, following the lead of T-DM1. This idea of “bombing” the tumor, once written off as a pipe dream by most people inside Genentech and academic research, has morphed into one of the company’s top strategies for fighting cancer, according to Sliwkowski, a longtime champion of the concept.

“We take this far more seriously than we did previously,” Sliwkowski says. “We are investing a lot of money and resources into this. That should answer your question.”

One of Genentech’s collaborators on antibody-drug conjugates, Seattle Genetics, says T-DM1 and another drug it is developing for Hodgkin’s disease called SGN-35, are at the forefront of a new wave of … Next Page »

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Calistoga Pharmaceuticals has come a long way in one year.

The Seattle-based biotech company made its first ripple on the national scene last year at the American Society of Clinical Oncology (ASCO), when it showed its novel drug for blood cancers caused tumor shrinkage in half of the first dozen patients tested. This year at the same confab, researchers led by Richard Furman of Weill Cornell Medical College in New York, had a much meatier set of results to show off. The early hint of effectiveness—and it was really just a hint last year—has much more solid confirmation now that 106 patients have been studied, and some longer-term follow up data is trickling in.

About 57 percent of patients with a slow-growing form of non-Hodgkin’s lymphoma had their tumors shrink by half or more, two-thirds with mantle cell lymphoma did that well, while 30 percent of patients with chronic lymphocytic leukemia had that response, researchers said yesterday at ASCO. Still, like any drug, this one has side effects. Researchers saw increasing rates of certain liver enzymes in the blood of patients who took high doses of the drug, which can be a warning sign of liver damage, something the FDA often monitors carefully. Calistoga says the side effect didn’t cause any observable liver symptoms in patients, and the enzyme levels returned to normal after doctors reduced the doses. (For a look at the detailed presentation slides, click here.)

“We have a clear signal now in terms of efficacy,” says Calistoga CEO Carol Gallagher.

Calistoga bears watching as one of the most promising privately held biotech companies in the Northwest. It raised $30 million in venture capital just a few weeks before it released the first glimpse of data at ASCO last year. The company is pursuing one of the prime targets in cancer biology today—the PI3 kinase pathway. Researchers are excited about this pathway because it is thought to control critical cell processes like proliferation, migration, and cell survival. When these normal functions get flipped into an overactive mode, it’s a hallmark of cancer cells spiraling out of control, or an immune system gone wild so that it attacks healthy tissue.

Carol Gallagher

Calistoga was founded in 2006 with some intellectual property from Icos to develop drugs against the PI3K enzyme. There are plenty of competitors in this hot field—including GlaxoSmithKline, Novartis, Roche, Exelixis, Oncothyreon, and Intellikine. Many of the rivals make drugs that hit a broad cross-section of PI3K enzymes, and Calistoga claims to be different because its lead candidate is made to hit a specific subtype of PI3 kinase, known as the delta isoform. The hope is that Calistoga’s lead drug, CAL-101, may have a better profile for blood cancers that express the delta isoform, and that it may have milder side effects, a useful feature if Calistoga wants to treat chronic conditions like inflammatory diseases.

The last time Calistoga talked publicly about CAL-101 was back in December at the American Society of Hematology meeting, when it had results from 57 patients. The easiest way to look at this updated data from 106 patients is through a chart, so that’s what I’m providing below. But a little background is required first. This study enrolled a wide variety of patients with blood cancers. More than half of them had relapsed or didn’t respond any more to existing therapies. Without receiving any other combination treatments, people in the study took CAL-101, a twice-daily oral pill, for a 28-day cycle of therapy, for as many as 12 cycles. Here is how patients responded in each group.

Response rates like that beg an obvious question: How long did the effect last? Cancer is … Next Page »

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Seattle-based Trubion Pharmaceuticals (NASDAQ: TRBN), the developer of targeted therapies for cancer and autoimmune diseases, said today it has won a patent dispute against Genentech and Biogen Idec. The dispute centers on targeted therapies designed to block a marker on cells, CD20, which is currently hit by Genentech and Biogen Idec’s rituximab (Rituxan). Trubion, which has developed its own CD-20 blocker, challenged a European patent held by Genentech and were successfully able to revoke it in September 2008. That ruling has now been upheld by a European appeals board, which had the final decision in the matter, Trubion said in a statement.

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Seattle Genetics has spent more than a decade thinking about cutting-edge biology, chemistry, and clinical trials to prove its drug candidates work. Then last week, for the first time in nine years I’ve been reporting on CEO Clay Siegall, he talked with passion about things like manufacturing, inventory, quality assurance, quality control, and insurance reimbursement.

It all might sound awfully boring. But it’s a sure sign that Bothell, WA-based Seattle Genetics (NASDAQ: SGEN), with help from its partner Millennium: The Takeda Oncology Company, is learning fast what it takes to be a mature, commercial biotech company. And while it may be a slow news period for Seattle Genetics (NASDAQ: SGEN), it has to grow up in a hurry, because it is only a few months away from finding out if it has really struck gold with a new therapy for Hodgkin’s disease and related lymphomas.

The big story at Seattle Genetics and Millennium centers on brentuximab vedotin, an “empowered antibody” that specifically seeks out cancer cells and unleashes a potent toxin on them for extra tumor-killing punch. This concept has not lived up to its hype over the past 30 years, but by the second half of 2010, Seattle Genetics and Millennium will learn from a pivotal clinical trial of 100 patients how well this therapy really helps sick patients. If successful, the companies will be able to seek FDA approval in early 2011, and potentially get a faster-than-usual six-month review that the agency sometimes gives to drugs with lifesaving potential. Patients, employees, investors, and an entire field of research is counting on Seattle Genetics and Millennium to deliver the goods. So Siegall & Co. are quietly trying to lay the groundwork now to make sure they are truly ready to make sure this drug is a hit.

Clay Siegall

“Our drug has a chance to be a very important drug for patients,” Siegall says.

For those just getting up to speed on this story, here’s a quick refresher. Seattle Genetics, founded in 1998, had its breakout moment in June 2008 at the American Society of Clinical Oncology meeting. That’s when the company released preliminary results showing its experimental treatment was able to completely wipe out or partially shrink tumors for 12 of 38 patients, with mild to moderate fatigue, cough, and nausea as side effects. Results only got better when researchers enrolled a few more patients, and longer-term follow-up data arrived.

A lot of things have fallen into place for Seattle Genetics as a business ever since that appearance at ASCO. It raced to the FDA in early 2009 with a proposal for a pivotal clinical trial, and won the agency’s blessing for the study design. The company got this trial up and running at 27 locations in North America and Europe, and completed enrollment six months ahead of schedule—a lightning pace in oncology, where it’s extremely difficult to enroll patients on time. The company raised more than $200 million from investors in 2009, during a dark period in the overall biotech financial market. In December, Millennium wrote a $60 million upfront check to Seattle Genetics to form a partnership, which left the smaller company with 100 percent of the commercial rights to the experimental drug in the North American market.

Much of what has happened since then has been the sort of behind-the-scenes blocking and tackling that biotech companies need to do, and often fail to do, as they prepare to commercialize a new drug. Part of that effort is in hiring new types of people, with skills in things like … Next Page »

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[Updated: 11:05 am Pacific] Scientists have been dreaming for a century about therapies that actively harness the power of the body’s immune system to kill cancer cells like an invading virus or bacteria. Today, Seattle-based Dendreon has made history by winning the first-ever FDA approval for this kind of cancer-fighter. Shares climbed 15 percent to $45.50 after the news broke.

The good news for Dendreon (NASDAQ: DNDN) came today when it received clearance from the FDA to start selling sipuleucel-T (Provenge) to men in the U.S. with terminal prostate cancer that has spread, even after prior rounds of standard hormone-deprivation therapy, according to a statement on the FDA website. The agency gave the green light after Dendreon showed in a trial of 512 men that patients lived a median time of 25.8 months if they got Provenge, compared to 21.7 months for those on a placebo. Patients on the drug had minimal side effects of fever and chills that lasted a couple days.

The FDA’s decision will have far-reaching impact for years. The drug is the first marketed product for Dendreon, which has piled up a deficit of more than $700 million in its 18-year development quest. The product is forecasted by analysts to exceed $1 billion in U.S. sales after a couple years on the market. Dendreon could morph into the regional anchor Seattle’s biotech community has lacked since Immunex was acquired by Amgen in 2002. For the 27,000 men in the U.S. who die each year from prostate cancer, the drug represents some hope for a longer life, and a higher quality of life alternative to chemotherapy. And for researchers, it offers new possibilities for a mode of treatment beyond surgery, chemotherapy, radiation, and targeted biotech pills and antibodies that must be taken chronically.

“This is a huge advance,” said Dr. John Corman, a urologist at Virginia Mason Medical Center in Seattle, and an investigator in Provenge clinical trials for eight years. “This is the first immunotherapy agent that’s been shown to provide a survival benefit for prostate cancer patients. And it’s a completely new class of therapy that provides remarkable opportunities for R&D.”

[Update with company statement.] Dendreon said the drug will be made available initially at about 50 medical centers in the U.S. The company didn’t say in its statement today how much it will charge for the drug, although it plans to hold a conference call with analysts and investors at 2:30 pm Eastern/11:30 am Pacific.

“The approval of Provenge is a significant step towards realizing our mission of transforming the lives of patients with cancer, and it also marks Dendreon’s transformation into a commercial enterprise,” CEO Mitchell Gold said in the statement.

While today’s FDA approval is groundbreaking, it’s worth being precise about what this means, and what it doesn’t. Treatments like Dendreon’s are most accurately referred to as “active immunotherapies,” although scientists sometimes loosely call them “cancer vaccines” in the media. Just to be clear, Dendreon’s product is a treatment that people get after they’ve already been diagnosed with prostate cancer, so it isn’t a vaccine in the traditional sense that prevents people from getting a disease. Because Dendreon’s treatment “teaches” the immune system to recognize certain cancer cells and fight them on its own, for months or even years, it’s considered an “active” immunotherapy. That’s also different from what researchers sometimes call “passive” immunotherapy. It’s fair to consider an intravenous-delivered antibody drug, like Roche’s rituximab (Rituxan), a “passive” immunotherapy because it works in part by stimulating the immune system to fight cancer cells, at least while the drug is active in the blood. It’s also fair to call Merck’s human papillomavirus vaccine (Gardasil) a cancer vaccine, because it prevents women from getting infected with a virus known to cause cervical cancer.

Whatever you choose to call Provenge, the anticipation of today’s FDA approval has already transformed Dendreon. A few weeks before the defining clinical trial data arrived in April 2009, the company’s stock was trading around $2, cash was running low, and it had about 200 employees. After the data arrived and was presented at a urology meeting in Chicago, Dendreon raised $630 million from investors, announced plans to grow to 600 employees, added two more drug factories, and saw its stock climb to more than $40 a share.

Plenty of questions remain about … Next Page »

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