Seattle Genetics Announces Pivotal Results in Lymphoma Drug Trial

Leukemia & LymphomaImage via WikipediaLymphoma news from Seattle Genetics hitting the web. This company is really making strides with Non-Hodgkin's Lymphoma drug Brentuximab. This drug is partnered with Takeda Oncology's Millennium. Takeda is a global pharmaceutical firm who specializes in Clinical Trials and marketing on a global scale. Brentuximab elicited 75% response rate in patients that had already rejected other cancer drugs, which is common.

Seattle Genetics expects a priority review from the FDA in the first half of 2011, and would like approval before 2012. The trial however was rather small at 102 patients. This drug is for patients with a very poor prognosis and don't have long to live. Seattle had said that a 25-30% response rate would likely gain a FDA approval. Seattle Genetics has a Special Protocol Assessment, so the FDA has already signed off on the trial's design.

An excellerated risk is associated with Seattle as follow-up trials could produce mixed results. I still like Seattle's chances and would invest in Seattle with cautious optimism as a run-up target for 2011 upon FDA approval. It will take a considerable ammount of time before that happens though. If approved this stock could be another Dendreon.

Wikinvest-Seattle Genetics (SGEN)

Seattle Genetics, Takeda Lymphoma Drug Shows Success

NEW YORK (Dow Jones)--Seattle Genetics Inc. (SGEN) said its novel blood cancer treatment, which attacks cancerous cells but ignores healthy ones, shrank tumors in three-quarters of patients with Hodgkin lymphoma, according to a study released Monday.

The results easily surpassed expectations and sent shares of Seattle Genetics up as much as 24% to a new 52-week high.

The drug, called brentuximab vedotin, in development with Japan's Takeda Pharmaceutical Co. Ltd. (TKPYY), is part of a next-generation of biotech therapies that aims to bolster chemotherapy's effectiveness while reducing its damaging side effects. For Seattle Genetics, the news comes two weeks after the company discontinued a different drug that failed to benefit patients with an aggressive form of blood cancer.

"Few agents have demonstrated this level of clinical response ... we are particularly encouraged by these results given that all patients had failed multiple lines of therapy," Chief Executive Clay Siegall said Monday.

The company plans to file for approval in the first half of 2011 using the data, with a potential launch in the second half. Takeda is talking with European regulators about submitting the data for approval next year.

Oppenheimer recently projected that peak annual sales of this drug for use in Hodgkin lymphoma would exceed $400 million. Seattle Genetics is also studying its use in earlier forms of the disease and in other blood cancers.

In the trial, which included 102 patients that had previously been treated, 75% of patients responded to the drug, with the median response exceeding six months.

The response is a combination of patients that had a complete response, which means their tumor disappears, and those with a partial response, meaning they had a 50% or greater reduction in their tumor. The company plans to present more complete data at a future scientific meeting.

Siegall said that a response of 30% or higher have been viewed as a success in the trial and Wall Street analysts were generally using the same benchmark.

Brentuximab vedotin is a different type of drug often referred to as an antibody conjugate. It is a cell-killing drug attached to a type of antibody so that the drug seeks the cancer, then kills it. The theory is that harmless cells aren't effected, thus lowering the drug's toxicity.

Chemotherapy, used since the 1950s, is usually given to a patient as a systemic treatment, meaning it travels throughout the entire body. While killing cancer cells, it also kills other cells and has other effects that often make patients very ill.

Brentuximab vedotin seeks a target called CD30, which is on the cell surface of several types of blood cancers, but is less common on normal tissue.

While the data shows the drug's success, analysts also highlight that it validates the company's technology related to making antibody conjugates and the future of such drugs.

Seattle Genetics has developed a linking mechanism that connects the cell-killing drug with the antibody so that they don't separate until they enter the tumor cell. The company licenses the technology, has 10 partners, and has collected more than $130 million in payments. It is also using the technology in a number of other drugs in its pipeline.

The link between the antibody and the chemotherapy is important. In June, Pfizer Inc. (PFE) pulled the only antibody conjugate drug that was on the market, a drug called MyloTarg that was approved in 2000. The leukemia treatment caused severe side effects and further research raised questions about its effectiveness. Many have blamed the drug's unstable linking technology for the toxicity.

Seattle Genetic said brentuximab vedotin's side effects were "generally consistent with prior clinical trial experience." A previous trial showed side effects including fatigue, fever, diarrhea and nausea.

The drug is similar in concept to Roche Holding AG's (RHHBY, ROG.VX) trastuzumab-DM1, or T-DM1, being developed with ImmunoGen Inc. (IMGN). That drug attaches a cell-killing agent to breast-cancer blockbuster Herceptin, but it recently had a setback when the FDA rejected its accelerated approval application. Roche expects to make a new submission by mid-2012.

Siegall stressed that the company has worked with the FDA in developing the trials for brentuximab vedotin and is confident of its path to potential approval. Furthermore, he said the delay for T-DM1 wasn't related to it being an antibody conjugate, but was more related the number of breast-cancer treatments already available.

The brentuximab vedotin study was conducted under a special protocol assessment, an agreement with the FDA on study design. The drug has orphan drug status in the U.S. and Europe, meaning the governments provide drug makers with incentives to develop new treatments for diseases with smaller patient populations.

Seattle Genetics and Takeda are also conducting several other trials of brentuximab vedotin, including a phase II trial for advanced anaplastic large cell lymphoma, another type of blood cancer, that is expected to have data in coming weeks.

Seattle Genetics shares recently rose 22% to $14.87. Earlier, the stock hit a year high of $15.08.

From Bloomberg News

Seattle Genetics, Takeda Drug Shrinks Lymphoma Patients' Tumors in Study
By Rob Waters - Sep 27, 2010 4:17 PM ET

Seattle Genetics Inc. said its two- drug therapy, developed with Takeda Pharmaceutical Co., cut tumor size by at least half in 75 percent of patients with Hodgkin’s lymphoma, a cancer of the immune system. Seattle Genetics rose the most in three years in Nasdaq trading.

The 102 people in the company-funded trial had advanced lymphoma and hadn’t been cured by previous treatments, said Clay Siegall, president and chief executive officer of Bothell, Washington-based Seattle Genetics. The benefit of the therapy lasted at least six months for most patients, he said.

The drug, SGN-35, uses an antibody to home in on cancer cells and deliver a payload of a cancer-killing agent. Seattle Genetics plans to submit a marketing application to the U.S. Food and Drug Administration in the first half of 2011, Siegall said. Approval would make it the first of a new generation of drugs that combine antibodies and anti-cancer agents, according to Jason Kantor, an analyst with RBC Capital Markets in San Francisco.

“Results were better than expectations, and we believe FDA approval in 2011 is highly likely,” Kantor said in a note today to clients.

Seattle Genetics rose $2.14, or 18 percent, to $14.30 at 4 p.m. New York time in Nasdaq Stock Market composite trading, the greatest single-day increase since January 2007. Takeda rose 0.5 percent to 4,030 yen in Tokyo trading today.

1,300 Deaths

About 8,500 people in the U.S. are diagnosed with Hodgkin’s disease every year and 1,300 die, according to the National Cancer Institute. Improved therapies have made Hodgkin’s more treatable in recent years, with about 85 percent of patients responding to the treatments, Siegall said. The 15 percent who don’t respond generally die within two to three years, he said.

The companies will seek accelerated approval for SGN-35 based on this study, the second of three rounds of testing generally required by U.S. regulators, because the medicine addresses an unmet medical need.

The trial aimed to see if the drug could cut the size of the tumor in half, called a partial response, or make it disappear, a complete response. Patients received an injection of the medicine, calibrated to their weight, every three weeks for up to 48 weeks.

Three-quarters of the patients had at least a partial response, according to a company statement. Siegall declined to be more specific and said a full report would be made at a future medical meeting.

‘Few Options’

“We believe the data are really promising for these patients who have a very poor prognosis and very few options,” Siegall said in a telephone interview yesterday. The drug “has the potential to be the first major advancement for treating people” whose cancer has returned or who didn’t respond to previous treatments, he said.

The company didn’t disclose rates of side effects. Some patients experienced fatigue; reduced white blood cell counts; diarrhea; nausea; and peripheral neuropathy, a nerve condition that causes pain and numbness in the limbs, Peggy Pinkston, a Seattle Genetics spokeswoman, said in an e-mail. The side effects in general weren’t severe, she said.

The drug, also known as brentuximab vedotin, is designed to use an antibody that recognizes and links to a receptor found on the surface of cancer cells and only minimally present or absent on healthy cells, Siegall said. Linked to the antibody is a drug that kills cells by keeping them from dividing and growing.

“It targets the cell population that we’re trying to eliminate without impacting, or only minimally impacting, normal tissue,” Siegall said.

Osaka, Japan-based Takeda is jointly developing the drug with Seattle Genetics and sharing development costs. Seattle Genetics will market the treatment in the U.S. and Canada and Takeda has rights in the rest of the world.

Seattle Genetics and Millennium Announce Positive Top-Line Brentuximab Vedotin (SGN-35) Data from Pivotal Trial in Relapsed and Refractory Hodgkin Lymphoma

-Objective Responses Achieved in 75 percent of Patients; Median Duration of Response Greater than Six Months-
-BLA Submission Planned in First Half of 2011-

BOTHELL, Wash. & CAMBRIDGE, Mass., Sep 27, 2010 (BUSINESS WIRE) --

Seattle Genetics, Inc. (Nasdaq: SGEN) and Millennium: The Takeda Oncology Company, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited (TSE:4502), today announced positive top-line results from the pivotal trial of single-agent brentuximab vedotin (SGN-35), an antibody-drug conjugate (ADC) targeted to CD30. The trial was conducted in 102 relapsed or refractory Hodgkin lymphoma (HL) patients.

Seventy-five percent of patients in the pivotal trial achieved an objective response as assessed by an independent central review, the primary endpoint of the trial. The median duration of response was greater than six months. The safety profile of brentuximab vedotin in this trial was generally consistent with prior clinical trial experience. A more complete data set will be presented at an upcoming scientific meeting.

"We are extremely excited with the top-line results, as they move us one step closer to our goal of bringing brentuximab vedotin to patients with relapsed or refractory Hodgkin lymphoma," said Clay B. Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. "We are positioned for a Biologics License Application (BLA) submission to the U.S. Food and Drug Administration (FDA) in the first half of 2011. In addition, we plan to report top-line data from our phase II trial of brentuximab vedotin in patients with relapsed or refractory systemic anaplastic large cell lymphoma (ALCL) within the next few weeks."

"The lack of adequate therapies for the treatment of relapsed and refractory Hodgkin lymphoma represents a substantial unmet medical need worldwide, with almost a third of the 30,000 newly diagnosed patients relapsing or becoming refractory to front-line therapy annually," said Nancy Simonian, M.D., Chief Medical Officer of Millennium. "These data have the potential to provide an important advance in therapy for Hodgkin lymphoma. We intend to discuss these results with European regulators to support our goal of submitting a Marketing Authorization Application to the European Medicines Agency (EMA) in 2011."

Pivotal Trial Design

The single-arm pivotal trial assessed efficacy and safety of single-agent brentuximab vedotin in relapsed or refractory, post-autologous stem cell transplant (ASCT) HL patients. Patients received 1.8 milligrams per kilogram of brentuximab vedotin every three weeks for up to 16 total doses. The primary endpoint of the trial was objective response rate as assessed by an independent review facility. Response assessments were based on the rigorous and internationally established Revised Response Criteria for Malignant Lymphoma (Cheson, 2007). Secondary endpoints included complete response rate, duration of response, progression-free survival, overall survival and tolerability. The trial was conducted under a Special Protocol Assessment (SPA) with the FDA and was discussed with the EMA during the process of obtaining EU Centralized Scientific Advice on the brentuximab vedotin development program. Brentuximab vedotin has been granted orphan drug designation by the FDA and EMA for the treatment of HL and ALCL and has been granted fast track designation by the FDA for HL.

About Brentuximab Vedotin

Brentuximab vedotin is an ADC comprising an anti-CD30 monoclonal antibody attached by an enzyme cleavable linker to a potent, synthetic drug payload, monomethyl auristatin E (MMAE) utilizing Seattle Genetics'
proprietary technology. The ADC employs a novel linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-expressing tumor cells. This approach is intended to spare non-targeted cells and thus may help minimize the potential toxic effects of traditional chemotherapy while allowing for the selective targeting of CD30-expressing cancer cells, thus potentially enhancing the antitumor activity.

In addition to the pivotal HL trial, Seattle Genetics and Millennium are conducting a phase II trial for relapsed and refractory systemic ALCL, a phase III clinical trial (the AETHERA trial) for patients at high risk of residual HL following autologous stem cell transplant, a phase II retreatment trial for relapsed patients who previously responded to brentuximab vedotin, and a phase I combination trial for front-line treatment of HL.

About Hodgkin Lymphoma

Lymphoma is a general term for a group of cancers that originate in the lymphatic system. There are two major categories of lymphoma: Hodgkin lymphoma and non-Hodgkin lymphoma. Hodgkin lymphoma is distinguished from other types of lymphoma by the presence of one characteristic type of cell, known as the Reed-Sternberg cell. A defining attribute of the Reed-Sternberg cell is its expression of the CD30 antigen.

According to the American Cancer Society, approximately 8,500 cases of Hodgkin lymphoma will be diagnosed in the United States during 2010 and more than 1,300 will die from the disease. Globally, there are more than 30,000 cases of Hodgkin lymphoma diagnosed each year. Although front-line combination chemotherapy can result in durable response rates, up to 30 percent of these patients relapse or are refractory to front-line treatment and have few therapeutic options beyond ASCT.
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