Diabetes drug Lilly abandoned has new life

Source: Indianapolis Business Journal

It could be called the one that got away.

Twelve years ago, officials at Eli Lilly and Co. pulled the plug on a much-anticipated experimental medicine for diabetes after it failed to prove effective at lowering patients’ blood sugar during a late-stage clinical trial.

It was a stinging disappointment. For more than a year, officials at the Indianapolis-based drugmaker had pinned their hopes on the drug, called teplizumab, to help turn the company around after a series of pipeline disappointments and a looming patent cliff on older medicines.

John Lechleiter, then-CEO, cited teplizumab as one of the three most promising experimental drugs in the company’s pipeline. Lilly had acquired the exclusive rights to the drug in 2007 from MacroGenics, a small biotech firm based in suburban Washington, D.C.

But Lilly’s high hopes came crashing down in October 2010 when an independent monitoring committee concluded that the drug failed to hit its goal, which was a composite of total daily insulin usage and blood-sugar levels in Type 1 diabetes patients. Lilly announced it was suspending the study while it determined what to do next.

“The failure to meet the primary endpoint is obviously disappointing for the millions of people who live with and treat type 1 diabetes,” Lilly said at the time. Shares in the drugmaker fell 5% on the news, and headlines underscored the defeat.

“More diabetes drug woes for Lilly as teplizumab fails,” said Pharma Times, an industry newsletter.

“In fresh setback, Lilly scuttles teplizumab program,” said Fierce Pharma, another industry newsletter.

But now, in an amazing resurrection, teplizumab is one of the hottest new drugs on the market. Last month, the U.S. Food and Drug Administration approved teplizumab, making it the first drug to delay the onset of late-stage type 1 diabetes in adults and child 8 years and older.

Some analysts say the drug could be a game-changing blockbuster, meaning it could ring up annual sales of $1 billion or more at its peak.

But this time, Lilly is on the sidelines. The company, which made a name for itself in diabetes in 1923 when it became the first drugmaker to commercialize insulin, gave up the rights to teplizumab shortly after it abandoned development.

A new home

Now, another company could be reaping the riches. In 2018, Provention Bio, a small biotech based in Red Bank, New Jersey, acquired the rights to teplizumab from MacroGenics for an undisclosed sum. And after a bumpy, four-year ride, filled with several temporary setbacks, the company is preparing to launch the drug under the brand name Tzield.

The drug does not cure or prevent diabetes, but studies show it can delay the onset of the most severe form of the disease by an average of two years.

“The drug’s potential to delay clinical diagnosis of type 1 diabetes may provide patients with months to years without the burdens of disease,” Dr. John Sharretts, the FDA’s director of diabetes, lipid disorders and obesity said in written remarks on Nov. 17.

For Lilly, the decision to give up on teplizumab to concentrate on other pipeline projects might come with a tinge of regret in light of the latest news. But the drugmaker is not publicly second-guessing things.

In a one-sentence statement to IBJ, Lilly pointed out that it continues to work on new diabetes treatments. It stayed away from commenting directly on teplizumab.

“Long-term prevention and/or treatment of type 1 diabetes continues to be an important priority for Lilly and we welcome all advancements in diabetes care that may improve outcomes for patients,” the company said.

For Lilly, of course, the picture is immensely brighter today than a decade ago. The company has launched new drugs for cancer, arthritis, pain and other maladies. Investors hope the company will launch new medicines in the next year or so for Alzheimer’s disease and obesity, two huge markets that could reap untold billions of dollars in sales.

Lilly’s stock has climbed sharply in recent years and is now trading in the $360 range, about 10 times higher than when it dropped teplizumab.

Not a strange route

And to be sure, the football bounce of teplizumab is not an isolated case. Around the world, pharmaceutical companies shelve or abandon experimental drugs every year for various reasons, including clinical results that don’t meet expectations, a change in company strategy or new regulations that shift the industry landscape.

Nine out of 10 experimental drugs that enter clinical trials fail to make it all the way to product launch, according to the American Association for the Advancement of Science. Even half of the experimental drugs that advance to the final stage of clinical testing will fail.

And in some of those cases, a drug will lie neglected for years before another company acquires it and tries its own set of tests.

“A drug being discovered by one company and commercialized by another happens frequently,” said Brian Stemme, CEO of Hoosier Cancer Research Network, a not-for-profit organization that helps oncologists design and execute clinical trials. “Drug discovery is a winding path, and there are so many variables that can impact this process that it’s almost inevitable that things will change significantly.”

Pharmaceutical companies often must make tough decisions about which drugs to advance in the clinic and which to shelve. Those choices often come down to a close study of the market, the competition and regulators as well as where the investment is most likely to pay off.

George Telthorst, director of the Center for the Business of Life Sciences at Indiana University, said drug companies have to consider constraints on their budgets and how many patients are most likely to be helped by a new product.

“It is not uncommon for pharmaceutical firms to trim their development portfolios and then have another firm pick up something,” he said.

Mary Mader, vice president of molecular innovation at the Indiana Biosciences Research Institute, an organization that helps academic and industry researchers develop inventions, said large drug companies often have a change in strategic direction that decreases their interest in an experimental drug.

“It’s not unusual for a pharmaceutical company to elect to discontinue the development of an asset for several reasons and then to sell it to another interested party that continues to do clinical development on it,” she said.

To read the full article, go to Indianapolis Business Journal.