Desmond-Hellmann arrived at Genentech at a time when the company was just realizing the power of its own pipeline drugs. It
had recently licensed Rituxan from IDEC, and the clinicians expected the drug to be modestly effective, but extremely safe.
But the tumors in the first patient treated with Rituxan broke down so fast—it was that effective—that the body could not
handle the toxic effects. "The patient's kidneys were threatened," she says. "The patient had medical difficulty as a result
of this tumor lysis syndrome."
Herceptin challenged researchers for another reason. Preclinical testing indicated that the drug only worked in one quarter
of the patients, but it appeared to be extremely effective for that small group. What the scientists needed to understand
was the genetic difference between the 25 percent of tissues that responded and the remainder that did not. Genentech found
that the drug was effective in the presence of the HER2 gene. When the scientists developed a diagnostic test to identify
patients with this gene, they were ready for the clinic. Without the diagnostic, the drug would have been effective in just
one in four patients and would have failed by traditional standards.
In this way, instead of becoming another abandoned compound, Herceptin opened the door to a new era of personalized medicine.
"She created what some people perceived to be almost impossible studies by targeting the drug against a very defined breast
cancer population," says Johnson. "There was a lot of skepticism: If the study, one, could be done and, two, was necessary.
Not only did they demonstrate it, but they did so with remarkable outcomes."
Desmond-Hellmann herself was inspired by what she learned from Herceptin. "It teaches you that the marker, HER2—which is kind
of like a competitive advantage for the tumor—can be identified and then turned into a treatment target. That the very asset
of the cancer turns into its Achilles' heel," she explains.
Herceptin was a major development when it launched, but it started to look even bigger this past year, when Genentech presented
new clinical results at the ASCO meeting. Herceptin was given to women with early-stage HER2-positive breast cancer in addition
to standard adjuvant therapy following surgery—chemotherapy, hormone therapy, or both—the risk of cancer recurrence was cut
"It showed that we have the opportunity to treat patients and have their cancer never come back," she says. "That's what we
ought to be doing." Desmond-Hellmann also notes that breakthroughs like this—which keep cancer in remission longer—edge medical
professionals toward managing cancer as a chronic disease.
"Now that Herceptin has shown its usefulness in that setting, we are talking about eradicating breast cancers, not just controlling
them," says Park.
Staying the Course
Of course, product development is never a sure thing. Over and over, promising molecules prove ineffective, or unexpected
dangers crop up in late-stage trials. For most pharma people, the hopeless mantra of "fail earlier" is about the best they
can hope for. What's admirable about Desmond-Hellmann is her seemingly instinctive ability to know when to ignore that advice,
and take risks.
"I would bet that instincts are just a form of data," says Hal Barron, chief medical officer of Genentech. "She always follows
When Desmond-Hellman was chief medical officer, back in 1997, Genentech began clinical trials of Avastin. Researcher Napoleone
Ferrara had demonstrated that an antibody directed at the vascular-endothelial growth factor (VEGF), the key regulator in
angiogenesis, could slow tumor growth in preclinical models. Angiogenesis—the process of creating new blood vessels—is an
important part of how tumors grow. So scientists hoped the drug would have wide application.
Genentech bet heavily on Avastin. But in September 2002, when the company had already invested more than $100 million in the
drug, bad news hit hard: The Phase III results of Avastin in late-stage breast cancer came back negative. The stock fell 10
percent in one day.
Desmond-Hellmann remembers the year as a time when she questioned what she was doing. Shareholders complained. Her clinical
trials budget was threatened. And the company as a whole understood the risk of losing Avastin.
"Some of your most important lessons come from adversity," she says. "When the Avastin breast cancer study was negative, there
was a lot of criticism about the amount of money we had invested, about what we were thinking. It provided me with a opportunity
to reflect on what we intended to do."
To get through those stressful times, says Desmond-Hellmannn, "You have to have a lot of confidence in the integrity of the
company. That's your anchor and your compass." To contend with pressures—like high prices and clinical setbacks—she says she
has " to be at a company that has good values, and wants to do good things for patients."
Desmond-Hellmann remained a realist. She didn't expect Avastin to work in all tumor types, but she was confident about anti-angiogenesis
because of the positive data generated in the preclinical work. The investigators on the study told her they still believed
in the drug as well—but they thought they were treating the patients too late.
"It reinforced for me the importance of working in a place where you really respect your colleagues, and you're very data
driven," says Desmond-Hellmann. "It also showed the power of listening, and getting input when something goes differently
than you wanted."
Desmond-Hellmann continued to roll out the studies. Finally, six years after clinical trials on Avastin commenced, in May
2003, the long-awaited colon-cancer data was announced. Avastin not only slowed tumor growth, but it also helped colon-cancer
patients live longer—an endpoint Desmond-Hellmann introduced to showcase the drug's effectiveness.
Desmond-Hellmann remembers the group assembled to enjoy that success. "There were ten of us or more in the room—Art [Levinson]
even called Napo Ferrara in Italy in the middle of the night to tell him that the trial had been successful," she recalls.
"For me, there was this sense that something important was going to happen for patients, and that I was part of this team
that was so talented, with different people doing very different things to contribute."
The clinical studies validated the strategy of angiogenesis, and in doing so, helped cement the future of Avastin and Genentech.
The stock did more than just jump at the news—it climbed 45 percent that day. Some analysts say Avastin is now set to be the
best-selling cancer drug of all time.
The cancer community has made it clear how highly it values the drug and Desmond-Hellmann's role in bringing it to market.
In 2005, she was elected as the first industry representative in more than 20 years to sit on the board of directors of the
American Association of Cancer Research. Margaret Foti, president of the association, compares Avastin to another ground-breaking
drug: "When we look at Gleevec [imatinib], one has to recognize that it would not be on the street without the sheer determination
of Alex Matter [the scientist who led the Gleevec effort at Novartis], who kept that drug in the forefront of the minds of
the people in the company. Susan did the same thing for Avastin."