Since the early 2000s, pundits have lamented that there is an innovation crisis in the pharmaceutical industry. One of the most common reasons given is the challenge of bringing new drugs to market.
The U.S. Government Accounting Office concluded in 2006 that the “productivity of [the pharma industry’s] research and development expenditures has been declining.” The cost of developing a new drug frequently tops $1 billion, and scores of drug candidates never make it to market.
The medical device industry has faced similar criticism for its focus on incremental innovation.
While the COVID-19 pandemic has heightened society’s appreciation for the pharmaceutical industry’s innovation, the concept of an innovation crisis hasn’t gone away.
Many of the arguments purporting such a crisis focus on the quality of pharmaceutical innovation rather than its quantity, said Troy Groetken, a shareholder, board member, and executive committee member at the intellectual property law firm McAndrews, Held & Malloy (Chicago). “Too many times, the problem we run into is the metric,” Groetken said.
It is common, for instance, for a trailblazing drug such as the cholesterol-lowering medication Lipitor (atorvastatin) to get credit for innovation. Winning FDA approval in 1996, Lipitor from Pfizer (NYSE:PFE) remains a popular statin or hydroxymethylglutaryl-CoA reductase inhibitor. Although Lipitor sales have fallen after the drug’s patent expiration in 2011, it remains one of pharma’s biggest blockbuster stories.
Lipitor gave rise to other similar drugs in the same class, but that doesn’t mean that all of them were copycats. “One of those that was extremely successful — not just from a financial standpoint but therapeutically was Crestor (rosuvastatin),” Groetken said. Winning FDA approval in 2003, Crestor is similar to Lipitor given its potential to treat high cholesterol and triglyceride levels. “Crestor was also quite innovative, but it doesn’t get counted because really it’s seen as a ‘me-too,’” Groetken explained. The developer of the drug, AstraZeneca (LON:AZN), is divesting European sales to Grünenthal.
One study found that Crestor lowered LDL cholesterol while increasing HDL cholesterol by a greater amount than Lipitor and two other statins. Patients tolerated the drugs similarly.
But Crestor rarely gets credit as an innovator even though it was “not an incremental advance,” according to Groetken.
Using counts of new molecular entities that won FDA approval is also a misleading innovation metric, Groetken said. “It looks at quantity, not the quality for innovation,” he said.
Admittedly, gauging pharmaceutical innovation should be a multifactorial endeavor. New classes of therapeutics, of course, deserve credit, as do drugs that offer therapeutic benefits over existing treatments within a category.
The molecular shape also can shed light on how innovative drugs are while also providing a framework for R&D. “You can break drugs down by shape or scaffolding,” Groetken said. Assessing a drug’s fundamental structure in two dimensions provides a basis for comparison to other similar compounds in compound libraries.
Such libraries’ growth enables more effective screening, allowing Big Pharma companies and smaller players to assess small molecule drugs more quickly. Similar libraries also exist for biotech.
“If you know the shape or you know the key aspects of that cellular molecule, you can search those and you can model with AI,” Groetken said.
The use of AI has accelerated R&D capabilities, making it possible to sift through ever-larger troves of data. “Think of it like a football field,” Groetken said. “In the past, we might look at one corner.” But with AI, you can look at the entire metaphorical field. “That is innovation,” Groetken added. “You can then accelerate which ones you think are going to be the most potentially effective therapeutically, bioavailability-wise, chemically and so forth.”
Filed Under: clinical trials, Drug Discovery, RD