BioMarin stories in this issue
BioMarin’s molecules yield miracles
BioMarin enzyme specialist speeds up science
BioMarin's five powerhouse 'orphan' drugs
BioMarin patient Kendra conquers MPS VI
SAN RAFAEL -- Charles "Chuck" O'Neill, Ph.D., vice president of pharmacological sciences at BioMarin Pharmaceutical, is an enzyme specialist who has been with the company 11 years after eight years with Genentech. His early training is in veterinary medicine, helpful in that early drug testing is done on rodents.
[caption id="attachment_102487" align="alignleft" width="199"] Charles O'Neill, BioMarin[/caption]
His work, with a team of 98 scientists in pharmacology out of a total of 160 in drug research, is to pin down details of a drug's use: how often and how much dosage, safety signals.
Because BioMarin tackles drugs for rare diseases, it needs a global presence just to find enough patients for clinical trials. "We don't get a lot of opportunities to do dose ranging, dose frequency, trying to figure out what the endpoints are," Dr. O'Neil said.
He aims to answer many such questions long before clinical trials, "which increases the speed of clinical development," he said. "We answer them in animal models. We are not investigating in a large number of trials in the clinic. We have to go around the world to get these patients."
Part of drug research is a "natural history" study of patients' experience of a disease. "We team up extremely well with patient advocacy groups," Dr. O'Neill said, such as the MPS Society, which serves all 11 types of MPS, and a family association for Batten disease (a mutated CLN2 gene), for which BioMarin has a drug in clinical trials.Ease Batten suffering
Batten, also called neuronal ceroid lipofuscinoses, is caused by a missing or "naked" enzyme and has barely 800 patients worldwide. Children with Batten suffer seizures, mental impairment and progressive loss of sight and motor skills. Most need wheelchairs and nearly always die -- blind, bedridden and unable to communicate.
BioMarin found striking positive results in animal trials on a Batten drug which is directly infused into cerebrospinal fluid in the lateral ventricle that "bathes the brain," Dr. O'Neill said. "We hitch on board at the headwaters of the river" to distribute the drug into 95 percent of the brain. The distributive technology will be useful in a new drug for MPS III-B, also called Sanfilippo syndrome.
In January 2013, San Rafael-based BioMarin acquired Zacharon Pharmaceuticals, based in San Diego, for its research on small molecules targeting pathways of glycan and glycolipid metabolism, "tags on the side of the enzyme that allow for entry into the cell," Dr. O'Neill said, which will be useful on the MPS III drug. "They were high-powered scientists," he said.
Gene therapy may eventually allow cells to manufacture missing enzymes inside cells instead of having the enzyme drug delivered from outside. But many of these diseases are caused by dozens if not hundreds of gene mutations.
Despite the tiny Batten patient population, "we have to move this thing forward," Dr. O'Neill said. "It's the right thing to do" because the disease causes such suffering.
[caption id="attachment_102541" align="alignright" width="333"] Isabel, a BioMarin patient with MPS VI, uses a wheelchair to get around and takes the company's Naglazyme to replace missing enzymes. She helped toss the first pitch at a Giants game in 2011, inspiring the team to win the World Series in 2012 and 2014.
(photo courtesy of BioMarin)[/caption]
"I don't think we're going to make a boatload of money off it, but the impact to these patients' lives -- think about clinicians who have to tell these patients and their families, you're doomed, you have a death sentence, you're going to be in a wheelchair in three years, dead by the time you're 12. It wears on even the physicians."
Finally, "we have some hope for you. It's nice to relay that," he said. "I wake up every day, I get to help kids. I've got the best job in the world."
"We are at the forefront of our field. I came here for the science," Dr. O'Neill said, and "for the ability to really affect lives rather rapidly. It's rewarding to move that fast."Isabel pitches for Giants
In 2005, he met a then 9-year-old MPS VI patient named Isabel at Children's Hospital Oakland. Without BioMarin's drug, "she would be severely disabled. She is a joy to be around. It is one of the greatest satisfactions," he said.
After the drug got approved, Isabel, who uses a tracheal tube to deal with breathing problems, came to a BioMarin party. "The biggest thrill was, she came up to me and tugged on my coat," he said. "She choked off her trach tube and said, 'Dr. O'Neill, thank you for the medicine.' If you can keep a dry eye on that -- if you don't think you're making an impact -- that's why we're here."
Isabel lives in Lafayette. In 2011, she helped Sergio Romo toss the first pitch at a Giants game. "We were like beaming fathers," Dr. O'Neill said.
