On December 6, 1994, Paul Bezy, a Genentech bioprocess technician, had finished a night shift followed by another six hours of overtime and was heading home, exhausted. It was afternoon, and he would be back to work again that second night, putting in long hours to produce more of a new medicine, trastuzumab (now known as Herceptin®), which was being developed as a potential treatment for HER2-positive metastatic breast cancer.
When he left the building, he was surprised by a group of protesters who were shouting, honking, lying on the street and banging on Genentech’s glass doors. The activists, members of the groups ACT UP, Project Inform and Breast Cancer Action, carried signs: “We need access, not excuses,” pleading for a medicine that had not yet been approved by the U.S. Food and Drug Administration (FDA). One of the protesters pounded in frustration on the hood of Bezy’s ’68 Mustang as he inched out of the lot.
At first, Bezy was confused. “We were working as hard as we could. What more could they be asking of us?” It wasn’t as if the company had copious amounts of the medicine that it was withholding; it could barely manufacture enough for clinical trials. “Herceptin is incredibly hard to make,” he says.
What Bezy knew, and many of the protesters at the time did not, was that making a batch of Herceptin was quite complex, not just a matter of stirring together chemicals. This particular biologic is made from antibodies to the HER2 receptors that promote the growth of certain types of breast cancer. To make a single batch of Herceptin requires growing trillions of monoclonal Chinese hamster ovary cells under very tight process conditions, with each cell producing only a minuscule amount of the antibody. After weeks of cell culture growth, the Herceptin is purified from the host cells using a series of steps that result in over a million-fold separation of the product from background contaminants. The company was already in the process of trying to dramatically ramp up its production of Herceptin, encountering roadblocks in machinery, engineering and chemistry along the way. “This was the first time anyone was scaling up antibody production, and each step was innovative and risky,” Bezy says.
As he drove away from the protesters, Bezy had an impulse to turn around and put in a few more hours. “I realized that if I put myself in the patients’ shoes, I would want access to this medicine, too. It was the most direct evidence that what we were doing really mattered to people’s lives.” Bezy, then a recent college graduate who is now the general manager and vice president of South San Francisco production at Genentech, says the moment of the protest marked a turning point for him.
“Before that event, I was working on cool technology and science,” he says. “After that day, everything I did was for the sake of the patients.” Every dose of the precious medication might make a difference to a cancer patient’s life, so Bezy and the production team kept working long hours.
Bob Erwin had intended to be at the protest that day, but stayed home with the flu. He’d participated in meetings to plan the event, and protesters carried photos of his wife, Marti Nelson Erwin, an obstetrician-gynecologist who had died of breast cancer less than a month before, on November 9.
Erwin, a scientist who worked in biotechnology, and his wife had been well-informed about the scientific advances that had led to this medication. They became involved with breast cancer advocates who had been schooled by HIV activists in influencing pharmaceutical companies and the FDA in speeding up clinical trials and treatment. Since Marti was young and her disease was aggressive, the Erwins were willing to try any treatment that held out hope. Although the FDA had not yet approved the medicine, they wanted to get their hands on it, for Marti and for other breast cancer patients. “As a family member, the worst you could think was that you didn’t do everything you could to help a loved one,” says Erwin.
The Erwins tried, through their physicians, to obtain the medicine from Genentech. Eventually, the company told them that before they could do anything Marti first had to find out whether she was HER2-positive, using a third-party lab they designated for accurate results. HER2 testing was a new technology and the process was still being defined. “It took months for the lab to complete the test and share the results,” Erwin recalls. They finally learned, in the last week of Marti’s life, that she was indeed HER2-positive. “By then it was too late,” says Erwin.
Marti’s death sparked the advocacy groups they’d worked with to take action. “They wanted to rattle the cage and use unconventional methods to generate a dialogue,” says Erwin. “Politeness didn’t work, so we’d have to raise our visibility and speak loudly.”
At the time, Genentech had little experience with patient advocates. The company didn’t yet understand the scientific and political sophistication of the advocacy groups. “Genentech didn’t have the people or infrastructure to deal with this new field they were getting into,” Erwin says. “But they went from being clueless to having a conversation very fast.”
Following the protests on Genentech’s campus in South San Francisco, the company set up meetings with breast cancer advocates and outside experts to discuss expanded access guidelines for the medication as well as the challenges with the supply of the medicine. The company invited Erwin to tour the manufacturing facilities to see firsthand how difficult the medicine was to make. “From that point on, my relationship with Genentech shifted from being adversarial to being constructive and collaborative,” says Erwin.
The sides didn’t often agree at first, but they gradually came to see each others’ points of view. The group met regularly, and eventually came up with a lottery system as the fairest way to give patients an opportunity to receive the limited quantities of the medication available. Over time, Genentech started to work with advocacy groups more closely, more like partners working together for the same cause rather than against each other. The relationship was mutually beneficial, with patient advocates even offering advice about how to design the clinical trials, and finding patients to enroll in them. Genentech, says Erwin, became a leader in the evolution of expanded access and compassionate use, and other companies have since looked to the company for guidance.
Eventually, the company scaled up enough to provide Herceptin to all patients seeking expanded access without a lottery system. On September 25, 1998, Herceptin was approved by the FDA for treating HER2-positive metastatic breast cancer as both a first-line therapy in combination with chemotherapy or alone in those who have received one or more chemotherapy regimens.1,2The approval happened just a few days before breast cancer activists had planned a big rally demanding FDA approval for the medicine in Washington, D.C. The rally turned out to be more of a victory celebration.
“It wasn’t fast enough to achieve what I wanted,” says Erwin, “but Genentech played a pivotal role in helping so many other women get the treatment they need to fight HER2-positive breast cancer.”
Read the full story behind Herceptin and Genentech’s other HER2-targeted medicines here.
What It Treats
Metastatic Breast Cancer
Herceptin has 2 approved uses in metastatic breast cancer:
- Herceptin in combination with the chemotherapy drug paclitaxel is approved for the first line treatment of Human Epidermal growth factor Receptor 2-positive (HER2+) metastatic breast cancer
- Herceptin alone is approved for the treatment of HER2-positive breast cancer in patients who have received one or more chemotherapy courses for metastatic disease
Patients are selected for therapy based on an FDA-approved test for Herceptin.
Important Safety Information and Serious Side Effects
Important Patient Safety Information
Possible Serious Side Effects With HERCEPTIN
Not all people have serious side effects, but side effects with HERCEPTIN therapy are common. Although some people may have a life-threatening side effect, most do not.
Your doctor will stop treatment if any serious side effects occur.
HERCEPTIN is not for everyone. Be sure to contact your doctor if you are experiencing any of the following:
These include heart problems—such as congestive heart failure or reduced heart function—with or without symptoms. The risk for and seriousness of these heart problems were highest in people who received both HERCEPTIN and a certain type of chemotherapy (anthracycline). In a study of adjuvant (early) breast cancer, one patient died of significantly weakened heart muscle. Your doctor will check for signs of heart problems before, during, and after treatment with HERCEPTIN.
INFUSION REACTIONS, including:
- Fever and chills
- Feeling sick to your stomach (nausea)
- Throwing up (vomiting)
- Pain (in some cases at tumor sites)
- Shortness of breath
These signs usually happen within 24 hours after receiving HERCEPTIN.
Be sure to contact your doctor if you:
Are a woman who could become pregnant, or may be pregnant
HERCEPTIN may result in the death of an unborn baby or birth defects. Contraception should be used while receiving HERCEPTIN and after your last dose of HERCEPTIN. If you are exposed to HERCEPTIN during pregnancy or within 7 months of becoming pregnant, you are encouraged to enroll in the MotHER Pregnancy Registry by contacting 1-800-690-6720 or visiting http://www.motherpregnancyregistry.com/ and report HERCEPTIN exposure to Genentech at 1-888-835-2555.
Have any signs of SEVERE LUNG PROBLEMS, including:
- Severe shortness of breath
- Fluid in or around the lungs
- Weakening of the valve between the heart and the lungs
- Not enough oxygen in the body
- Swelling of the lungs
- Scarring of the lungs
Your doctor may check for signs of severe lung problems when he or she examines you.
Have LOW WHITE BLOOD CELL COUNTS
Low white blood cell counts can be life threatening. Low white blood cell counts were seen more often in patients receiving HERCEPTIN plus chemotherapy than in patients receiving chemotherapy alone.
Your doctor may check for signs of low white blood cell counts when he or she examines you.
Side Effects Seen Most Often With HERCEPTIN
Some patients receiving HERCEPTIN for breast cancer had the following side effects:
- Feeling sick to your stomach (nausea)
- Throwing up (vomiting)
- Infusion reactions
- Increased cough
- Feeling tired
- Shortness of breath
- Low white and red blood cell counts
- Muscle pain
You should contact your doctor immediately if you have any of the side effects listed above. You are encouraged to report side effects to Genentech and the FDA. You may report side effects to the FDA at 1–800–FDA–1088 or http://www.fda.gov/medwatch. You may also report side effects to Genentech at 1–888–835–2555.
Please see additional select Important Safety Information throughout, and the full Prescribing Information, including Boxed WARNINGS.
1. FDA. Herceptin Metastatic Breast Cancer Approval Letter. http://www.accessdata.fda.gov/drugsatfda_docs/appletter/1998/trasgen092598L.pdf. September 25, 1998. Accessed May 26, 2017.
2. Herceptin Prescribing Information. South San Francisco, Calif.: Genentech, Inc. 2017.