It takes the S&P 500 index on average around seven years to double. But plenty of stocks deliver 100% gains in a much shorter period of time. And some even triple or more.

We asked three Motley Fool contributors to pick biotech stocks that have tripled or more so far this year. Here's what they had to say about Cassava Sciences (SAVA -0.85%), Ocugen (OCGN -6.58%), and BioNTech (BNTX -4.08%).

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Risk-averse investors should look elsewhere

Prosper Junior Bakiny (Cassava Sciences): Shares of Cassava Sciences have soared by roughly 800% since the beginning of the year -- a terrific performance and one which the company owes to Simufilam, an investigational medicine for the treatment of Alzheimer's disease (AD). Positive data from an open-label study for the company's leading candidate, coupled with the unexpected approval of Biogen's AD drug Aduhelm, helped propel Cassava Sciences stock this year. 

The biotech is now moving ahead with this program. In October, it started a phase 3 study for the investigational medicine. The trial will enroll 750 AD patients with mild and moderate cases of the disease, and test the safety and efficacy of Simufilam over 52 weeks. Cassava Sciences is also planning to start another late-stage clinical trial before the end of the year. The company seems to be firing on all cylinders, but I'd still avoid this stock.

For one, Simufilam wouldn't be the first promising potential AD medicine to fail in a couple of pivotal clinical trials. It could succeed, and the upside for Cassava Sciences would be huge if it does. But as a clinical-stage biotech, the company has no products on the market, and its performance will depend on the perceived success or failure of Simufilam in these upcoming studies. Even if it produces strong results in the lab, unforeseen regulatory setbacks have sunk more than a few promising clinical-stage biotechs.

Furthermore, the AD market could look very different from how it looks today by the time Simufilam earns approval, if it ever does. The launch of Biogen's Aduhelm has been disappointing so far, but sales of the therapy could speed up. Eli Lilly recently announced it had initiated a rolling submission to the Food and Drug Administration (FDA) for its investigational AD drug, donanemab. The pharma giant expects a regulatory decision as early as the second half of 2022. Cassava Sciences could make headway into this market despite the competition, but an increasingly crowded space could also limit the company's upside. 

In short, after more than doubling this year, Cassava Sciences' future remains uncertain. Aggressive investors might consider initiating a small position in the stock. But for the risk-averse, it's better to watch from a safe distance for now. 

A meme stock that's taken investors on a wild ride

David Jagielski (Ocugen): Buying shares of a meme stock that's popular with retail investors can put your portfolio on a bit of a wild ride. And that's exactly what's happened with Ocugen investors in 2021. If you bought the stock at the beginning of the year, you'd have more than quadrupled your money by now. However, Ocugen's share price has plunged close to 50% below its high three times this year -- most recently over the last few weeks.

The company doesn't yet have a product that it can sell to customers. The stock's immediate success hinges on the fate of Covaxin, the COVID-19 vaccine it's co-developing with the Indian company Bharat Biotech. Ocugen only shares in the profits that will come from the vaccine in Canada and the U.S., although neither country has approved the vaccine, even for emergency use.

The good news is that with the FDA recently announcing that mixing and matching booster shots is acceptable, Covaxin will have an opportunity to penetrate the market in the U.S. even if vaccination rates climb higher (currently, they're at around 60%). Ocugen has filed for Emergency Use Authorization (EUA) of Covaxin in the U.S. for children between the ages of two and 18. It has also submitted an Investigational New Drug application that would allow it to conduct a phase 3 study for a broader Biologics License Application which, if approved, could make Covaxin available to adults.

Ocugen hasn't generated any revenue this year. That might not change anytime soon unless Covaxin gets the nod from the FDA or Health Canada.

A positive development could quickly send Ocugen's stock higher. There's the potential to earn a great return on Ocugen's stock, but it's a gamble at best. Investors who have made a profit might want to consider selling. There's definitely plenty of room for the stock to fall: Multiple analysts have recently set price targets for Ocugen that are at least 25% below its current price.

A big shot in the COVID-19 market

Keith Speights (BioNTech): Like Cassava and Ocugen, BioNTech has more than tripled investors' money so far this year. The stock's huge gains are due to the tremendous success of Comirnaty, the COVID-19 vaccine that BioNTech markets with Pfizer.

Nearly everything that could go right has gone right for BioNTech. Comirnaty is the best-selling COVID-19 vaccine in the world. It's picked up approvals or authorizations in every country where BioNTech and Pfizer have submitted regulatory filings so far. The company is now highly profitable with a fast-growing cash stockpile.

Can this great momentum continue? It's a definite maybe. The biggest unanswered question for BioNTech is whether or not COVID-19 boosters will be needed on an ongoing basis after the pandemic ends. If annual boosters are required, the stock could move higher, although not nearly at this year's pace.

However, there's a possibility that the demand for COVID-19 vaccines won't be as great in the future. One wild card is the likely availability of oral COVID-19 therapies, including Pfizer's Paxlovid. BioNTech CEO Ugur Şahin said in his company's third-quarter call that he doesn't think these pills will have "a huge impact" on vaccination rates. But he acknowledged that BioNTech will need to closely watch what happens.

Unfortunately, BioNTech doesn't have any other late-stage candidates in its pipeline that could be in a position to enter the market relatively soon. However, the company has four programs in phase 2 testing, two of which are fully owned and two that are in partnership with Roche

BioNTech's prospects over the next few years are at least somewhat murky. Of these three high-flying biotech stocks, though, I think it has the best chance of continuing to perform well.