Before sunrise on February 22, 2013, Alexander Hardy, a Genentech vice president at the time, was already in his office. He was waiting to hear if a new medicine that he was hoping to launch was going to be approved by the U.S. Food and Drug Administration (FDA).
He wasn’t the only one.
At the University of California, Los Angeles (UCLA) Jonsson Comprehensive Cancer Center, Dr. John Glaspy was anxious to give the medicine to a woman whose metastatic breast cancer was so advanced she had already been told to put her affairs in order and begin hospice care. She had exhausted all treatment options and was desperate. But the approval could be hours, or even days away and time was running out.
Then, at 6:30 a.m., Genentech received an email from the FDA saying the agency had approved Kadcyla® Indication and Important Safety Information, an antibody drug conjugate for people with HER2-positive metastatic breast cancer that had spread to other parts of the body after prior treatment with Herceptin® and taxane chemotherapy.1,2 Getting FDA approval was a long-awaited achievement, but there was still work to do. Now Genentech had to get the medicine into the hands of doctors like Glaspy, as fast as possible.
Kadcyla carries a boxed warning for serious liver and cardiac risks associated with the medicine, as well as the potential to harm an unborn baby. Kadcyla is not the same medicine as trastuzumab (Herceptin). Indication and Important Safety Information
The lag time between FDA approval and getting a medicine to physicians and patients can sometimes be months, as the company manufactures, packages and distributes the medicine. But Hardy’s team knew patients were waiting for this medicine. “The level of excitement from the physician and patient advocacy community was tremendous,” Hardy says, “like nothing I had seen in my career.” So, they had been strategizing a plan to get the medicine to physicians and their patients right away.
That plan had involved a lot of risks. The development and manufacturing of a new, complex medicine like Kadcyla are just some of the first hurdles. Making a batch of Kadcyla takes 18 months and involves over 18,000 miles of travel as its different components are created, purified, dehydrated and packaged in different facilities around the world. All of this had to be done before the FDA even approved the medicine.
Roger Symczak, the Genentech product team leader for the global supply chain, had his team set up numerous contingency plans for potential snags in the production, FDA approval process and launch of Kadcyla. “We had to plan much further ahead than we typically do,” he says. “There is much greater risk that you won’t be able to meet demand when you have to look ahead 18 months.”
Even with the medicine ready to go, the packaging can be the last hold-up. After months of discussion and proposed language, when the FDA sends an approval letter, they can request a wide variety of changes to the product label, from safety language to artwork and even punctuation—which can sometimes take up to a month to redo. The team at Genentech’s manufacturing site in Hillsboro, Oregon had gone through the late-stage packaging process “at risk,” taking the chance that they may have to reprint and repackage. All their careful consideration paid off, as the FDA accepted the final label as is.
Once Kadcyla was approved by the FDA, the team found a way to send the medicine directly to UCLA, expediting the usual supply chain process. So just 11 hours after the approval–following decades of research–the first vials of Kadcyla had shipped. Hardy watched and waited, tracking the package’s journey from the manufacturing site in Hillsboro, Oregon to Dr. Glaspy and his patient.
“When it was finally scanned at UCLA, I got an email, and it was just fantastic,” says Hardy. Everyone who had heard about the shipment was excited. Genentech’s local account representative even waited at the hospital to make sure the vials were delivered. Dr. Glaspy used that first vial of Kadcyla to treat his patient that weekend. Indication and Important Safety Information
That first box of Kadcyla now sits framed—and empty—on Hardy’s office wall in Basel, Switzerland, where he is now head of global product strategy for Roche. He’s held on to it as he moved across three continents in his career at Genentech and Roche. “It’s a reminder that at the end of the day, there are people waiting desperately for these medicines,” he says. “It’s amazing what we can achieve while staying within the rules and processes. That should be an inspiration for people.”
Read the full story behind Kadcyla and Genentech’s other HER2-targeted medicines here.
What it Treats
KADCYLA is approved to treat HER2-positive breast cancer that has spread to other parts of the body (metastatic breast cancer) after prior treatment with trastuzumab (Herceptin) and a taxane. Prior treatment could have been for the initial treatment of breast cancer or for the treatment of cancer that had spread to other parts of the body.
Important Safety Information
What is the most important safety information I should know about KADCYLA?
KADCYLA is not the same medicine as trastuzumab (Herceptin).
- KADCYLA may cause severe liver problems that can be life-threatening. Symptoms of liver problems may include vomiting, nausea, eating disorder (anorexia), yellowing of the skin (jaundice), stomach pain, dark urine, or itching
- KADCYLA may cause heart problems, including those without symptoms (such as reduced heart function) and those with symptoms (such as congestive heart failure). Symptoms may include swelling of the ankles or legs, shortness of breath, cough, rapid weight gain of greater than 5 lb in less than 24 hours, dizziness or loss of consciousness, or irregular heartbeat
- Receiving KADCYLA during pregnancy can result in the death of an unborn baby and birth defects. Birth control should be used while you receive KADCYLA and for 7 months after your last dose of KADCYLA
- If you are exposed to KADCYLA during pregnancy or become pregnant within 7 months of your last dose of KADCYLA, contact your healthcare provider right away; you are also encouraged to enroll in the MotHER Pregnancy Registry by calling 1-800-690-6720 or visiting http://www.motherpregnancyregistry.com/
- You are also encouraged to report exposure to KADCYLA during pregnancy, or if you become pregnant within 7 months of your last dose to Genentech by calling 1-888-835-2555
- If you are a mother who is breastfeeding, you should talk with your doctor about either stopping breastfeeding or stopping KADCYLA
Contact your doctor right away if you experience symptoms associated with these side effects.
What are the additional possible serious side effects of KADCYLA?
- KADCYLA may cause lung problems, including inflammation of the lung tissue, which can be life- threatening. Signs of lung problems may include trouble breathing, cough, tiredness, and fluid in the lungs
- Symptoms of an infusion-related reaction may include one or more of the following: the skin getting hot or red (flushing), chills, fever, trouble breathing, low blood pressure, wheezing, tightening of the muscles in the chest around the airways, or a fast heartbeat. Your doctor will monitor you for infusion-related reactions
- KADCYLA can cause life-threatening bleeding. Taking KADCYLA with other medications used to thin your blood (antiplatelet) or prevent blood clots (anticoagulation) can increase your risk of bleeding. Your doctor should provide additional monitoring if you are taking one of these other drugs while on KADCYLA. Life-threatening bleeding may also happen with KADCYLA, even when blood thinners are not also being taken
Low Platelet Count
- Low platelet count may happen during treatment with KADCYLA. Platelets help your blood to clot. Signs of low platelets may include easy bruising, bleeding, and prolonged bleeding from cuts. In mild cases there may not be any symptoms
- Symptoms may include numbness and tingling, burning or sharp pain, sensitivity to touch, lack of coordination, muscle weakness, or loss of muscle function
Skin Reactions Around the Infusion Site
- KADCYLA may leak from the vein or needle and cause reactions such as redness, tenderness, skin irritation, or pain or swelling at the infusion site. If this happens, it is more likely to happen within 24 hours of the infusion
How will my doctor know if KADCYLA is right for me?
You must have a HER2 test to determine if your cancer is HER2-positive before taking KADCYLA, because benefit has been shown only in patients whose tumors are HER2-positive.
What are the most common side effects of KADCYLA?
The most common side effects seen in people taking KADCYLA are:
- Pain that affects the bones, muscles, ligaments, and tendons
- Low platelet count
- Liver problems
You are encouraged to report side effects to Genentech and the FDA. You may contact Genentech by calling 1-888-835-2555. You may contact the FDA by visiting www.fda.gov/medwatch or calling 1-800-FDA-1088.
Please see the full Prescribing Information for additional Important Safety Information, including most serious side effects, at www.kadcyla.com.
1 FDA. FDA approves new treatment for late-stage breast cancer. http:www.fda.gov/newsevents/newsroom/pressannouncements/ucm340704.htm. February 22, 2013. Accessed September 20, 2016.
2 Kadcyla Prescribing Information. South San Francisco, Calif.: Genentech, Inc. 2016.
Title Photo: The packaging team surrounds the box as it leaves the manufacturing site in Hillsboro, Oregon, on its journey to UCLA and a waiting patient.
This article was originally published at the “Article” source noted above and distributed by The Tutu Project for informational purposes only.Tags: Food and Drug Administration, Genentech, Indication (medicine), Jonsson Comprehensive Cancer Center, Liver, Medicine, metastatic breast cancer, Neu!, Trastuzumab, Trastuzumab emtansine