Image via WikipediaArticles Today about Roche's partnership with ImmunoGen on TDM-1. TDM-1 is a highly targeted cancer drug for Breast Cancer.
The data from the TDM-1 phase II study in front-line breast cancer patients are early and very preliminary, but also encouraging because they suggest TDM-1 may be the next-generation successor to Herceptin that Roche has been looking for.
ImmunoGen, as Roche's partner on TDM-1, stands to profit as well if the drug is approved and successful.
In the phase II study, 137 women with HER2-positive metastatic breast cancer with no prior chemotherapy were randomly assigned to treatment with TDM-1 or Herceptin plus the chemotherapy drug Taxotere.
After six months of follow-up, the overall response rate for patients treated with TDM-1 was 48% compared to a 41% response rate for patients treated with Herceptin-Taxotere.
More striking was the difference in the rate of adverse events between the two drugs. The rate of "clinically relevant" adverse events (defined as Grade 3 or higher) was 37% in the TDM-1 arm compared to 75% in the Herceptin-Taxotere arm.
A full presentation of the T-DM1 study will be made Monday at the European Society of Medical Oncology (ESMO) annual meeting taking place in Milan.
Roche CEO Severin Schwan called the TDM-1 data "stunning" at a press event in Tokyo, according to a Reuters story Friday.
ImmunoGen shares were up 6% to $7.09 in late Friday trading.
T-DM1 is a so-called "armed antibody" that combines the targeted antibody drug Herceptin owned by Roche (already a potent cancer drug on its own) with a chemotherapy payload developed by ImmunoGen.
TDM-1 is designed to deliver a cancer-killing dose of chemotherapy directly inside tumors, sparring healthy cells from toxic side effects. This may explain the sharply lower toxicities observed in the front-line breast cancer study of TDM-1 compared to Herceptin-Taxotere.
For instance, the rates of hair loss and neutropenia (low white blood cell counts) in the Herceptin-Taxotere arm were 66% and 57%, respectively. By comparison, hair loss and neutropenia were reported in 1.5% and 7.5% of TDM-1 patients, respectively.
More patients treated with TDM-1 reported fever and nausea than those treated with Herceptin-Taxotere.
The TDM-1 data to be presented Monday are preliminary and may not hold up as the phase II study progresses. The study's primary endpoint is progression-free survival, which will determine whether TDM-1 can significantly delay the time before a patient's tumor starts to grow compared to Herceptin-Taxotere.
Roche, however, is not waiting for final results from this phase II study to push ahead with TDM-1 development in front-line metastatic breast cancer. A large, phase III study comparing TDM-1, Herceptin and another Roche drug, pertuzumab, has already been announced.
The TDM-1 data to be presented Monday may also help ease the sting felt in August when the U.S. Food and Drug Administration rejected Roche's effort to seek approval for T-DM1 based on results from a different phase II study involving patients with more advanced breast cancer.
--Written by Adam Feuerstein in Boston.
Roche: breast cancer, lung cancer data "stunning"
Fri Oct 8, 2010 4:46am EDT
* Breast cancer drug data could turn sentiment after setback
* Shares have fallen 21 pct this year on Avastin worries (Adds background)
TOKYO Oct 8 (Reuters) - Data for a Roche Holding AG (ROG.VX) breast cancer drug and a lung cancer drug set to be presented at a European oncology conference that starts later in the day was "stunning", the Swiss drugmaker's chief executive said on Friday.
Roche is set to unveil data on T-DM1, a breast cancer drug and MetMab, a treatment for lung cancer as well as on the use of Avastin, the company's top-selling drug, in ovarian cancer patients.
Battered by recent setbacks for key medicines, Roche is banking on a batch of upcoming clinical trial data to restore belief in its pipeline.
"I think a lot of people will be very excited about what we have to present," said CEO Severin Schwan. "I think the T-DM1 results are stunning; MetMab results are stunning," he added.
The head of the world's leading cancer drug company was speaking in Tokyo after a presentation to reporters and analysts hours ahead of the annual meeting of the European Society for Medical Oncology (ESMO) in Milan. The meeting will take place from Oct. 8 to 12.
The data on T-DM1 could help turn sentiment on an experimental drug whose image was tarnished in August when U.S. regulators rejected Roche's bid to gain marketing approval based only on mid-stage Phase II trials.
T-DM1 is viewed inside Roche as a key product. It is not only a potential improvement on the established blockbuster Herceptin but also the first of a new kind of "armed antibody" that can carry a cell-killing payload into cancer cells.
Shares in Roche have fallen 21 percent this year, making it one of the worst performers in the global large-cap drugs sector, following doubts about Avastin's future in breast cancer and other problems. [ID:nLDE69419V]
The company announced in July that Avastin helped women with ovarian cancer live longer without their disease getting worse in a Phase III study, but analysts are anxious to see the details in order to model accurately the commercial opportunity
New cancer data may be tonic for sickly Roche
Tue Oct 5, 2010 11:41am EDT
* Roche drugs in focus at Oct 8-12 European cancer congress
* Ovarian cancer study could lift Avastin sales forecasts
* Roche filing for ovarian use in EU by end 2010, U.S. 2011
* Results due also with T-DM1 "armed antibody" at congress
By Ben Hirschler
LONDON, Oct 5 (Reuters) - Swiss drugmaker Roche (ROG.VX), battered by recent setbacks for key medicines, is banking on a batch of upcoming clinical trial data to restore belief in its pipeline.
News on Avastin in ovarian cancer and new drug T-DM1 in breast cancer will be closely watched by both investors and cancer doctors at the annual meeting of the European Society for Medical Oncology (ESMO) in Milan from Oct. 8 to 12.
Roche also hopes to impress experts with mid-stage clinical trial results of PLX4032, a new kind of pill against skin cancer, at a melanoma conference in Sydney next month.
"In the next few days and until the year-end we will see numerous highly exciting data on new molecular entities and line extensions," Stefan Frings, the company's leader for Avastin, told a Jefferies pharmaceuticals conference on Tuesday.
Roche certainly needs a pick-me-up. Its stock price is down 20 percent this year, making it the worst performer in the global large-cap drugs sector, following doubts about Avastin's future in breast cancer and other product setbacks.
The company announced in July that Avastin helped women with ovarian cancer live longer without their disease getting worse in a Phase III study, but analysts are anxious to see the details in order to model accurately the commercial opportunity.
Good clinical trials data could add $500 million to $1 billion to sales forecasts for Avastin, a product which sold $6 billion worldwide in 2009 as a treatment for bowel, breast, lung and other cancers, analysts believe.
Frings said Roche would file for European regulatory approval of Avastin in ovarian cancer by the end of the year, with a U.S. submission following in 2011.
For graphic on Avastin sales: r.reuters.com/deb89n
For Special Report on Roche: r.reuters.com/sed24p
"It's important, after all the setbacks Roche has had, that we are going to see more and more mid-stage clinical data to rebuild confidence in this part of its pipeline," said Vontobel analyst Andrew Weiss.
"It is important to remember this is not an imploding company. It is a research company."
ARMED ANTIBODY
The data on T-DM1 could help turn sentiment on an experimental drug whose image was tarnished in August when U.S. regulators rejected Roche's bid to gain marketing approval based only on mid-stage Phase II trials.
T-DM1 is viewed inside Roche as a key product. It is not only a potential improvement on the established blockbuster Herceptin but also the first of a new kind of "armed antibody" that can carry a cell-killing payload into cancer cells.
"It really does work. We have very strong Phase II data," Frings said.
The recent U.S. Food and Drug Administration decision was a disappointment and delayed T-DM1's path to market by two years. But, if anything, the setback increased its value, he added.
"We now have the opportunity, if those (Phase III) data pan out, to file in an earlier setting -- so not last-line but second-line -- and thanks to (President Barack) Obama healthcare any biologic now earns 12-year exclusivity, so the NPV (net present value) for us has gone up," Frings said.
After Milan, Roche will present keenly awaited Phase II data on its new melanoma drug at the International Congress of the Society for Melanoma Research in Sydney from Nov. 4 to 7. The drug has produced startling strong results in early tests, although its effect may be temporary.
ESMO: New Agent Shows Promise in Advanced Breast CA
By Ed Susman, Contributing Writer, MedPage Today
Published: October 08, 2010
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco
MILAN -- An investigational trastuzumab combination agent showed promise in the treatment of advanced breast cancer when compared with trastuzumab (Herceptin) plus docetaxel (Taxotere), researchers reported here.
In the study, slated for presentation Monday at the meeting of the European Society for Medical Oncology, the antibody-drug conjugate known as trastuzumab-DM1 not only produced a better response rate among patients with HER2-positive metastatic breast cancer, but also appeared to cut the rate of side effects in half.
About 37% of patients taking trastuzumab-DM1 experienced clinically-meaningful adverse side effects compared with 75% of those taking the taxane, Edith Perez, MD, of the Mayo Clinic in Jacksonville, Fla., said in a press release.
After a median of approximately six months of follow-up, Perez and her colleagues found an overall response rate of 48% in patients administered trastuzumab-DM1, compared with 41% in the trastuzumab plus docetaxel arm.
The researchers enrolled 137 women in the study, 67 of which were treated with the experimental drug. All the women had performance status scores of 1 or 2. All participants had HER2-positive metastatic cancer, with no prior chemotherapy for their metastatic disease.The median age of the women on trastuzumab-DM1 was 55 years. The taxane group median age was 52.
Trastuzumab-DM1 is the first antibody-drug conjugate. It binds together two existing cancer drugs with the aim of delivering both drugs specifically to cancer cells -- trastuzumab, a monoclonal antibody that targets cells that overproduce the protein HER2; and DM1, a chemotherapy agent that targets microtubules.
"This is the first ever presentation of an anti-HER2 antibody-drug conjugate used as first-line therapy for patients with advanced breast cancer," Perez said in the press release. "We are encouraged by the results. The study demonstrated that T-DM1 has very good anti-tumor activity as well as much lower toxicity when evaluated side by side with the older 'standard'."
The combination has shown promising activity in preclinical studies. Other clinical trials have also shown it to be effective in patients whose advanced cancer has not responded to other treatments. "This trial represents the logical step -- moving the drug up to patients with newly diagnosed HER2-positive metastases," Perez reported.
The trial is ongoing and the positive outcomes are generating enthusiasm for a larger phase III trial now underway. "This trial is named MARIANNE, and it evaluates taxane plus trastuzumab against T-DM1 as administered in this study, with a third option being T-DM1 plus pertuzumab, another novel anti-HER2 agent," the statement said.
The results are important for two reasons, commented Fabrice André, MD, from Institut Gustave Roussy in Villejuif, France, in the same press release. "Firstly, they confirm that in coming years chemotherapy could be replaced by a less toxic compound. Indeed, in the present study, the rates of serious adverse events were much lower in patients given T-DM1 compared to the chemotherapy arm. These results suggest that, with the same efficacy, T-DM1 could dramatically reduce the toxicities related to chemotherapy."
The second important implication of this study is that it proves the concept that linking a monoclonal antibody to a cytotoxic drug leads to an anticancer effect. "This could have several implications beyond drugs that target HER2," Dr André reported.
Perez wrote in her abstract that hard endpoints including overall survival in the Genentech-sponsored trial will be reported in 2011.
No comments:
Post a Comment
Note: Only a member of this blog may post a comment.