From Staff Reports
Westfield, N.J., —
A trio of Merck scientists who led the discovery and development of a first-in-class treatment for type 2 diabetes have been honored as "Heroes of Chemistry" by the American Chemical Society.
Nancy Thornberry, Ann Weber and Joe Armstrong were one of two teams inducted this year into this scientific "hall of fame" for their central roles in the creation of Januvia, a medication that has helped millions of type 2 diabetics control their blood sugar. The researchers accepted the award on Sunday at a ceremony during the ACS National Meeting in Boston.
Armstrong, 49, is the son of Norma Armstrong of Tarboro and a 1978 graduate of Tarboro High School.
“Through close collaboration with our external partner Solvias, our team discovered a completely new transformation: the asymmetric catalytic hydrogenation of unprotected enamines,” Armstrong said.
“This methodology is now being applied to numerous synthetic efforts of other chiral molecules containing this important biologically active scaffold and highlights Merck's commitment to chemistry innovation and scientific excellence.
“Not only did we improve our yield by 50 percent, and reduce waste by 80 percent, which will likely eliminate up to 330 million pounds of waste during the lifetime of the drug, we also completely eliminated aqueous waste from the process.
Thornberry, senior vice president and franchise head for Diabetes and Obesity, initiated the dipeptidyl peptidase-4 (DPP-4) inhibitor program in 1999 and, along with Ann and Joe, co-led the discovery efforts. Ann, vice president of Chemistry, led the medicinal chemistry team that discovered sitagliptin phosphate, the active ingredient in Januvia. Joe, senior director, Process Chemistry, led the team that discovered and developed an unprecedented, sustainable "green" process for synthesizing the active ingredient.
Each year, the ACS, the world's largest scientific society, bestows its "Heroes of Chemistry" award to chemists and their companies whose inventions have advanced chemical research, and improved human life.
The society also considers commercial success of the products, because, as they assert, good business results follow good science.
Januvia is all of the above. The compound helps control blood sugar levels by blocking dipeptidyl peptidase IV, or DPP-4, an enzyme that breaks down the incretin peptides that activate insulin production after a meal. By inhibiting DPP-4, Januvia enables those peptides to stimulate the release of insulin for a longer period of time, thereby lowering the glucose level in the blood.
When Januvia came to market in 2006, it was the first new oral therapy for the treatment of type 2 diabetes in more than a decade. The unmet medical need was significant. Januvia provides a new treatment option to help patients reach their glycemic goals and feel healthier.
The Januvia program was among the fastest from initiation to registration in Merck history. The company started substantially behind the competition, yet was able to deliver a first-in-class molecule to market in about 3.8 years, half the industry average.
Januvia and the more recently approved Janumet (sitagliptin combined with metformin) continue to deliver substantial value to the company, achieving $1.9 billion and $658 million, respectively, in sales last year. Nancy aims to keep the program flourishing with an extensive, clear strategy for lifecycle management, including multiple fixed dose combinations, and through the initiation of a cardiovascular outcomes study.
"A major part of our strategy now is to focus on mechanisms that will be complementary to that of Januvia and that may offer a cardiovascular benefit since that's such a major goal in the treatment of diabetes," said Thornberry said.
"We all came to Merck to improve human health," she adds. "We are very privileged to be a part of this program and we are extremely proud of the product."
Armstrong came to Merck in 1990, and in 2001 he began working on the sitagliptin team. Currently senior director, Discovery and Preclinical Sciences Integration Office, he co-chaired a team with Thornberry that formulated the early clinical development strategy for Januvia. They initiated a first-in-man study just six months after the compound had been approved as a preclinical candidate.
Armstrong also led a team of chemists who developed an innovative synthesis that reduced waste and created a shorter and more efficient manufacturing process. As a result, the overall yield was increased by nearly 50 percent, and the amount of waste was reduced by over 80 percent
Armstrong was accompanied to the black tie event by his wife Helen, mother and Aunt Cornelia Thompson.
Joe and Helen live in Westfield, N.J., with daughters Madeleine,11, and Kathryn, 9.
