The foundation’s grants to Vertex and a smaller company it acquired led to the development of Kalydeco, which was approved in 2012. It is the first drug that treats the underlying cause of cystic fibrosis rather than just the symptoms, slowing the rate of decline in lung function. Vertex, which is based in Boston, is testing two other drugs that have also shown promise in clinical trials. Wall Street analysts project that the family of medicines could eventually have sales of several billion dollars a year.

Rather than receiving royalties on sales of those drugs over the next two decades, the foundation decided to cash in now so it could have more money to put into research quickly. So it sold the rights to future royalties to Royalty Pharma, an investment firm that specializes in buying such assets, for a one-time $3.3 billion payment. Royalty will profit if, over time, the royalties amount to more than it paid.

Executives at Royalty Pharma say it is by far the largest payment ever made for pharmaceutical royalties. The next-biggest transactions were worth around $700 million each, including one in which Royalty Pharma acquired half the future royalties owed to Northwestern University for the invention of the pain and epilepsy drug Lyrica.

Image Kalydeco treats the underlying cause of cystic fibrosis.

Pablo Legorreta, chief executive of Royalty Pharma, said, “This will demonstrate to many research organizations that by getting the royalties they can fuel their future investments.”

In the past, disease foundations might have supported only academic research. But many are now following the lead of the Cystic Fibrosis Foundation in getting involved with companies — an approach often called venture philanthropy.

“If we wanted to get therapies to patients faster, we needed to be partnering with the industry that actually brings those drugs to patients,” said Louis J. DeGennaro, chief executive of the Leukemia & Lymphoma Society. Other organizations pursuing venture philanthropy include JDRF (formerly the Juvenile Diabetes Research Foundation), the National Multiple Sclerosis Society and some groups involved in muscular dystrophy.

Some organizations do not ask for royalties, saying that the return they seek is merely getting a drug to market. But increasingly they are asking for financial returns as well.