More than 300 completely new medicines, vaccines and treatments for more than 150 conditions have entered the U.S. market since 1990, with a raft of benefits for consumers.
The need for many surgeries has been reduced; survival rates are higher; quality of life has improved. Indeed, between 1986 and 2000, the average life expectancy for Americans and others around the world increased by a full two years, and a big chunk of that gain — roughly 40 percent — comes from pharmaceuticals, according to the Pharmaceutical Research and Manufacturers of America (PhRMA).
Those rich rewards don’t come easily, however. For every 10,000 compounds that enter the R&D (research and development) pipeline, only one ultimately makes it to market, PhRMA says. The whole process takes an average of 10 to 15 years for a single drug, and the average cost per drug is US$800 million to $1 billion.
Today there are more than 2,000 new drugs coming through the pipeline. Which of those hold the most promise to do the most good?
Steps in the Pipeline
The road to market for pharmaceuticals is a long one, with many steps along the way. The process begins with the discovery or creation of a molecule that holds potential to treat some health problem.
Those with the most promise — just 250 or so out of the original 5,000 to 10,000 compounds — then go on to preclinical trials, which are essentially aimed at making sure the compound is safe enough to undergo human testing.
From there, only about five of the original batch are allowed to progress to clinical trials with human volunteers. These trials take six to seven years and occur in three consecutive stages: Phase 1, with 20 to 100 volunteers; Phase 2, with between 100 and 500; and Phase 3, with 1,000 to 5,000 volunteers involved in testing.
When a potential medicine clears those trials, its manufacturer typically submits a “new drug application” (NDA) to the Food and Drug Administration (FDA). The drug then gets reviewed by the FDA — a process that can take up to two years — and, if it’s approved, makes its way to market. On average, only one of the original 5,000 to 10,000 that began the process make it this far.
Of course, once a drug has made it through the process and gained FDA approval, other companies don’t have to start from scratch to get approval for their own versions of the same compound. Rather, they can submit an abbreviated NDA (ANDA). For example, since approval of the first two NDAs for 200 milligram ibuprofen tablets in the 1980s, between 20 and 30 ANDAs have been approved for other companies to market the same product, Karen Mahoney, a spokesperson for the U.S. Food and Drug Administration’s Center for Drug Evaluation and Research, told TechNewsWorld.
Drugs that have been on the market a long time ultimately get converted into monographs, which are like “recipe books” for the drug, she added. By adhering to the monograph, manufacturers can market their own version of the drug without seeking FDA approval.
In the Works
All the major pharmaceutical firms have many drugs at various stages of the pipeline. Eli Lilly is no exception, and four of the medications it is currently working on hold particular promise, William Chin, vice president of discovery research for the company, told TechNewsWorld. “We’re very excited about these,” he said.
First on Chin’s list is a potential new drug for schizophrenia that targets a receptor known as “mGlu2/3.” Eli Lilly already has another drug, called “Olanzapine,” that also treats schizophrenia, but it — like many antipsychotics — tends to cause weight gain and can be associated with diabetes, Chin explained.
“What’s exciting is that we’ve recently obtained Phase 2 data from a relatively small study that showed this new substance was equally effective without the side effects,” Chin said.
“We’d like to repeat that study, but for this stage, it’s very, very interesting,” Chin said. Eli Lilly is now gearing up for pivotal trials on the potential new drug.
Also in the works at the company are two drugs that focus on Alzheimer’s disease. “It’s a terrible disease, and right now there still aren’t very good therapies,” Chin said. “We need to define drugs that slow or even prevent the disease.”
It’s been found that the abnormal accumulation of a protein called “Abeta” in the brain plays a key part in Alzheimer’s. Lilly’s two new drugs in this area attack the problem in two different ways: One by preventing synthesis of the protein in the first place, and the other by removing the excess once it’s been made.
The first approach uses an inhibitor of an enzyme called “gamma secretase” that is known to be critical in the synthesis of the Abeta peptide. The second uses an antibody against Abeta.
“Both have gotten good data in early Phase 2,” and Lilly will probably begin pivotal trials early next year, Chin said.
Help for Diabetics
Last is a project that stems from a strategic partnership between Eli Lilly and MacroGenics to work on an antibody against a protein called “CD-3” that’s critical in the regulation of immune responses, Chin said. The new compound shows particular promise in preventing the progression of Type 1 diabetes, he said.
“People with Type I diabetes are typically on insulin for life,” Chin explained. “By having this therapy alter the immune response, we think we might be able to help patients with this disease.”
Merck is another pharmaceutical giant with a bevy of promising new medicines in the pipeline, though its top contenders currently target an array of different diseases.
First, Cordaptive is an investigational compound containing extended-release niacin and laropiprant that is designed to help treat atherosclerosis, Ian McConnell, a spokesperson for Merck, told TechNewsWorld.
An NDA has already been filed with the FDA for the drug, which has been found to reduce LDL-cholesterol levels, increase HDL-cholesterol levels, and reduce triglyceride levels in patients. It also produces fewer flushing symptoms than other therapies, McConnell said.
Merck is also working on a cancer-fighting compound called “MK-8669,” also known as “deforolimus.” The drug, an investigational novel mTOR inhibitor, is part of a collaboration between Merck and Ariad and is currently in Phase 3 development for the treatment of metastatic sarcomas, McConnell said.
Migraine sufferers may get relief from MK-0974, an investigational oral calcitonin gene-related peptide (CGRP) receptor antagonist currently in Phase 3 development. By blocking a peptide that gets released during migraine attacks, the drug takes a new approach to pain relief and so is particularly exciting, McConnell said.
Merck’s Taranabant, also in Phase 3 development, is a potent and orally bio-available acyclic CB1R inverse agonist currently being investigated for the treatment of obesity. The drug has been shown to decrease food intake and increase energy expenditure, McConnell said.
Finally, Odanacatib is about to begin Phase 3 studies to investigate its ability to treat osteoporosis. The compound is a highly selective inhibitor of the cathepsin K enzyme, which is believed to play a role in both osteoclastic bone resorption and in degrading the protein component of bone, McConnell said. By inhibiting the enzyme, Odanacatib uses a different approach to treating osteoporosis than most current drugs do, he added.
There’s no telling yet which of these drugs will make it to market, or how long that might take. However, America’s pharmaceutical and biotech research companies are spending more than ever on new drugs and vaccines, including last year’s record-setting level of $55.2 billion, according to PhRMA. It’s a pretty safe bet that consumers will soon reap the rewards.