Gaucher’s Disease is a recessive genetic disease particularly prevalent among Ashkenazi Jews. The head of the National Organization of Rare Diseases (NORD) was of Ashkenazi Jewish descent and two of her four children had the disease. We tested her oldest son Brian and his disease was advancing so quickly that he might die before we had our therapeutic approved. Brian’s internal organs were swelling with accumulating lipids, which if not reversed, would likely lead to a series of painful and expensive surgeries and an early death. We received permission from the FDA to make Brian the first patient in our Phase I/II clinical trial, which is normally a safety trial, but instead to give him a big enough dose to potentially save his life. Our scientists worked frantically to collect enough human placentas to make enough Ceredase to clear Brian’s accumulated lipids. Finally we had enough material late on a Friday and our lead scientist Scott agreed to fly the therapy to Washington to infuse Brian the following Monday.
That weekend there was a power outage in Chinatown. We had a backup generator for just such a situation but it failed to come on as intended. By Sunday morning, when Scott checked in at his lab, the frozen therapeutic had begun to thaw, potentially destroying the entire batch. He froze it back down and hoped for the best. Scott flew it frozen to Washington DC and began Brian’s week long treatment late the next day with considerable trepidation. Brian seemed to respond immediately and by the end of the week we had our first full remission from disease. Brian would need periodic infusions the rest of his life, but his spleen had shrunk to normal size, liver function was good, and it looked like this disease would not end his life. This was what we had been hoping and working for all these years.
Then we went back to work to prepare enough material to test the next three patients in our Phase I/II trial. In the following months we would infuse each of the three additional patients but none of them showed the kind of dramatic response we had seen in Brian. This was worrying. Brian also appeared to be accumulating lipids once again. The follow-on infusions from the newer batches of material were just as pure and potent but didn’t seem to have the same ability to clear lipids. Anyone reasonably experienced clinical research team would likely have abandoned this as a failed therapeutic at this point. Not Genzyme. Not given our culture.
Scott went back into the lab to experiment whether that power outage had somehow improved the enzyme’s ability to be taken up in the cellular macrophages. It turns out it did. The enzyme has a chain of carbohydrates attached to its surface, and bringing it above freezing had cleaved the outer most two, exposing a sugar that preferentially is taken up by macrophages. Modifying his production process to include this new knowledge allowed us to make product that worked splendidly for all these patients. They now showed the same lipid clearance and physiological improvement. We had our first proprietary therapy and also had discovered a whole new therapeutic strategy in terms of carbohydrate remodeling of enzymes. Ceredase, and Genzyme’s subsequent recombinant form Cerezyme, would become billion dollar drugs, creating new cures where none had been possible before, due to our science and our culture.