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Roche Holding AG.

Roche Holding AG. (Gianluca Colla/Getty Images/TNS)

The 25 people in Roche Holding AG’s obesity pill study would barely be enough to field both sides of a soccer match. Yet their weight loss added $16.8 billion to the Swiss drugmaker’s market value in a day, only the latest in a series of big share moves based on success in tiny trials.

Positive results in the earliest stages of development have driven about $93 billion in market value gains this year for obesity-drug makers, according to Bloomberg calculations. That optimism is due to the size of the obesity market, with shareholders buying into a chance at even a small slice of a pie that Goldman Sachs Group Inc. says could reach $130 billion by 2030.

Those kinds of numbers aren’t in play for experimental drugs being developed for other types of diseases, said Gareth Powell, head of health care at Polar Capital. His team has £3.6 billion ($4.65 billion) under management and holds stakes in obesity-drug developers Zealand Pharma A/S, Eli Lilly & Co. and Amgen Inc.

“The reason this is so different is because the end market size is just so big,” Powell said. “You just do the math.”

What may be getting lost in the frenzy - driven by the blockbuster success of weight-loss drugs from Novo Nordisk A/S and Lilly - is the notoriously fickle nature of pharmaceutical development.

Success in an early-stage trial is by no means a guarantee that a medicine will reach the market. In fact, more than half of all drugs that cleared the first clinical hurdle between 2011 and 2020 flunked out once they were tested in more patients, according to a study published by an industry trade group.

Some of the biggest recent moves have come from studies that executives touted on conference calls with investors without publishing data. When Novo Nordisk discussed positive results from a weight-loss pill in 16 patients in March, investors added $48.6 billion to the company’s market value.

Though it technically came in a mid-stage study, another case cited by many investors and analysts is Amgen. Robert Bradway, the US biotech’s chief executive officer, said he was very encouraged by interim results from the experimental drug MariTide in May, without giving details. Nonetheless, investors piled $17.7 billion onto the company’s market capitalization.

“I’ve been kind of blown away at some of the stock reactions,” said Jared Holz at Mizuho Securities in New York. “I think we’re in store for more of it.”

A typical investor calculation might work like this, according to Mizuho’s Holz: If the potential market is worth at least $100 billion, a drug that could capture just 5% of that market would have annual sales of $5 billion. Based on a simple sales multiple, the company or asset that could generate those sales would be worth somewhere between $15 billion and $25 billion, he said.

Investors also see a high likelihood that Big Pharma players looking to get into the space will buy up biotechs, further elevating the smaller companies’ prices.

Another reason for investor confidence is that weight loss is a very clear result for a study, even a small one, said Manu Chakravarthy, Roche’s global head of cardiovascular, renal and metabolism product development. “If you see it, you see it,” he said. “If you don’t, you don’t. It’s not one of those things where you’re trying to guess, does this drug work or not.”

An early-stage trial may not show the full picture of a new obesity asset, but it will show some important factors such as whether a drug is oral or injectable, how often it’s dosed and an indication of how well it might work, said Tommy Sternberg, an equity research analyst at William Blair Investment Management. “You start to get clues,” he said.

Context is important too, Powell said. For a company like Roche, which had traded at a low earnings multiple after a series of high-profile failures in Alzheimer’s disease and cancer, an early-stage success in obesity could pressure investors to reconsider their position on a stock, he said.

“It does drive a change in outlook,” he said. “They have to question why they don’t own it.”

Big moves on small obesity trials will probably continue until competition becomes stiff enough that investors perceive less chance for new players to take share in the market, according to Powell, Holz and others. But for now, many still see plenty of room to grow.

“It’s the first time we have good products showing strong efficacy” for obesity, Gregoire Biollaz, senior investment manager at Pictet Asset Management, said of the existing drugs from Lilly and Novo. “It’s difficult to speak about a bubble with the data we’ve seen so far.”

With assistance from Madison Muller.

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