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.
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 to seek approval for the product in Europe in 2011. “These data have the potential to provide an important advance in therapy for Hodgkin lymphoma,” said Millennium’s chief medical officer, Nancy Simonian, in a statement.
The trial, which started in February 2009, was designed in collaboration with the FDA. All patients got the treatment, rather than being randomly assigned to either the standard of care or the new drug. They were given an intravenous infusion of the Seattle Genetics treatment every three weeks. Side effects were mostly mild, and similar to what researchers saw in a preliminary trial: mild tingling and numbness in the fingers and toes, fatigue, white blood cell depletion, and diarrhea. All patients had relapsed after prior therapy and generally had a life expectancy of two to three years.
Seattle Genetics—partly to give its investigators a chance to show the full details at medical conference to be determined—isn’t providing important details yet about how many of the patients had complete disappearance of their tumors and how many just had partial responses. But when Seattle Genetics’ executive team got a look at the data over the weekend, it confirmed what they thought they’d see, given results from a Phase I trial. Back in a story I wrote two years ago, chief medical officer Tom Reynolds said brentuximab vedotin offered the kind of groundbreaking results for a cancer drug that are rarely seen, likening it to Roche and Biogen Idec’s rituximab (Rituxan) for non-Hodgkin’s lymphoma and Novartis’ imatinib (Gleevec) for chronic myeloid leukemia. Yesterday, Siegall had the same reaction.
“When the data was put up on screen, excitement was palpable,” Siegall says. “It was incredibly exciting for us. We work incredibly hard and are passionate about what we do. I can’t tell you how gratifying it is to see that kind of result. Very few agents demonstrate this type of response rate.”
More news is to come on whether this drug can help patients earlier on or with similar diseases. Seattle Genetics plans to release more clinical trial data within a few weeks on whether brentuximab vedotin can help patients with another rare lymphoma, anaplastic large cell lymphoma, that also has an overabundant number of CD30 cell markers, like Hodgkin’s. And while many patients with Hodgkin’s are essentially cured today by prior rounds of chemotherapy, Seattle Genetics and Millennium envision bringing this new antibody therapy to larger numbers of patients with earlier forms of disease because of the new drug’s combination of strong effectiveness and mild side effects. One such trial, called Aethera, is currently enrolling more than 320 patients.
Seattle Genetics hasn’t set a price for this product, but it has discussed hypothetical prices with analysts in the past as they try to get a handle on the market opportunity. Potential patients number 6,000 to 8,000 in the U.S., plus a similar number in Europe, according to Seattle Genetics market research. If the drug cost $45,000 to $50,000 per year, it could generate $300 million to $400 million in sales, Siegall told me in June 2008.
Over the weekend, Siegall said “it could command a premium price” based on the strength of the clinical trial data, although it’s still too early to set the actual price. This is one of the important questions Seattle Genetics will have to work on in the year ahead, along with other key tasks to complete. The to-do list will include getting the FDA application ready, preparing for an FDA advisory panel meeting, presenting at medical conferences, building up manufacturing inventory, and continuing the momentum with enrollment in early stage trials. Siegall talked with me about this all-out commercial push, and how Seattle Genetics was getting ready to handle all this work, in a feature story about the company’s growth in May.
Today’s results validate the long-term technology strategy of Seattle Genetics: to make targeted antibody drugs. The company was founded in 1998 with technology that Bristol-Myers Squibb gave up on: genetically engineered Y-shaped proteins that can be made to hit certain targets on cancer cells, while mostly sparing healthy ones. That is a big advantage over traditional chemotherapy that can be brutal on healthy cells and cause nasty side effects.
But many antibodies have failed over the years. While they might interfere with tumor growth and proliferation, they sometimes lack the potency to create a true knockout punch. For three decades, scientists have tried to add toxins to the antibodies to essentially create targeted chemotherapy, with very little to show for it. Earlier generations of these so-called “antibody-drug conjugates” failed, often because the toxin would break off in the bloodstream before it could reach the intended target. Wyeth (now part of Pfizer) introduced the first “empowered antibody,” gemtuzumab (Mylotarg), back in 2000, but it was a commercial dud because of its side effects, and Pfizer recently pulled it off the market.
Seattle Genetics has sought to improve on drugs like that through the years with a “synthetic linker” technology that keeps the antibody and toxin stable in the bloodstream, releasing the potent payload only into the tumor. The Seattle Genetics technology has been licensed for development on certain cell targets by a number of major pharma and biotech companies, such as GlaxoSmithKline, AstraZeneca’s MedImmune unit, Daiichi Sankyo, Bayer, and Roche’s Genentech unit. Seattle Genetics has retained exclusive rights to the technology’s use in hitting specific targets, and two other candidates against those targets are now in clinical trials.
Roche’s Genentech unit, the world’s leading maker of antibody drugs, has been in hot pursuit of this same concept for years, and also has produced some strong results with a more potent version of its pioneering breast cancer antibody, trastuzumab (Herceptin). That new potent antibody, called T-DM1, uses a different linking technology provided by Waltham, MA-based ImmunoGen (NASDAQ: IMGN). T-DM1 has been at the forefront of development for such empowered antibodies although the drug hit a bump in the road in August, the FDA said it wouldn’t review a Genentech application until it sees results from a more thorough test.
That setback for Genentech means that Seattle Genetics could be in position during 2011 to establish the new paradigm of empowered antibodies. If this drug is cleared by FDA, it will send a ripple effect through the biotech industry, given that “naked antibodies” that lack the extra degree of potency already make up a market worth an estimated $30 billion a year. Once the first of the new empowered antibodies hits the market, analysts will be busy sizing up the pipeline of more to come in the industry, and projecting all new growth curves for this class of drug.
“We think ADC [antibody-drug conjugate] technology is here to stay, and it could be really important for cancer patients and potentially transformative,” Siegall says. “These data establish us as the leaders in ADC technology. We are certainly not going to be sitting back and watching. We are going to push hard and make sure we provide the most promising opportunities for patients with limited therapeutic options.”
From a business perspective, Siegall is dreaming big. “We are now in position to transition from an R&D company into a commercial company. We’re looking forward to growing this company, and building an important biotech company. What’s an important biotech company; how do you define that? To me, it’s a company that makes products that patients really need.”
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