We're past the halfway point in 2019. And there have been plenty of big winners among biotech stocks so far.

Despite the threat of restrictive changes to the ability of biotechs to set drug prices and rumblings of a single-payer system in the U.S., at least 20 biotech stocks have doubled or more as of July 10. But the five best biotech stocks of 2019 so far have quadrupled or more. Here are the biotech stocks that have outperformed all others this year.

Bar chart with blue line trending up and 2019 in front of the chart.

Image source: Getty Images.

1. Axsome Therapeutics

Axsome Therapeutics (AXSM -1.36%) might deserve the nickname "Awesome Therapeutics" based on its stock performance. Shares have skyrocketed more than 800% so far in 2019.

The biotech kicked off the year with great news from its phase 2 study of experimental drug AXS-05 in treating major depressive disorder (MDD). Axsome followed up in April with another success for AXS-05 in meeting the primary endpoint of a phase 2 study for smoking cessation.

In addition, the Food and Drug Administration (FDA) decided to allow an expedited approval path for the drug in treating MDD. All of this good news has made for a great year so far for Axsome.

2. Provention Bio

Shares of Provention Bio (PRVB) are up more than 500% year to date. The big catalyst for the clinical-stage biotech was its announcement in June of results from a study sponsored by the National Institutes of Health (NIH). Those results found that a 14-day course of Provention's experimental immunotherapy PRV-031 delays the onset of type 1 diabetes in high-risk individuals by at least two years.

That wasn't the only good news for Provention this year. In April, the biotech initiated a phase 3 clinical study evaluating PRV-031 in treating patients with recent-onset type 1 diabetes. The company also completed enrollment in its phase 2 study of experimental drug PRV-6527 in treating Crohn's disease. 

3. Adverum Biotechnologies

Adverum Biotechnologies (ADVM -1.70%) stock has soared more than 390% so far in 2019. Shares have steadily risen throughout most of the year but really kicked into high gear in May when the FDA lifted a clinical hold on one of the patient cohorts in a phase 1 clinical study evaluating Adverum's gene therapy ADVM-022 in treating wet age-related macular degeneration.

It didn't take long for Adverum to get the ball rolling with the lower-dose cohort in that phase 1 study that was previously on hold. The biotech dosed the first patient in June. In the meantime, Adverum has seen what it calls "a robust preliminary anatomical response" and no serious adverse events with the first cohort of patients receiving a higher dose of ADVM-022. Results from the first patient cohort are expected later this year.

4. Zynerba Pharmaceuticals

Shares of Zynerba Pharmaceuticals (ZYNE) have zoomed more than 380% higher year to date. And not for just one reason. Zynerba has enjoyed at least four major catalysts so far in 2019.

The biotech received a new U.S. patent for treating Fragile X syndrome (FXS) with cannabidiol (CBD) in February. In late April, Roth Capital analyst Jerry Isaacson issued a very positive opinion on Zynerba stock. That was followed just a few days later by the FDA granting fast track designation to Zynerba's CBD gel Zygel in treating FXS. And in June, Zynerba won another new patent for treating autism spectrum disorders using synthetic CBD, causing its stock to skyrocket even more.

5. Arqule

Arqule (ARQL) stock has more than quadrupled thus far in 2019. Shares jumped in March after the biotech reported its 2018 fourth-quarter results and provided positive guidance for its cash position at the end of the current year.

But the best news for Arqule came in June. The biotech reported promising results from a couple of early stage clinical studies for experimental hematology drug ARQ 531 and rare disease drug miransertib. Even when Arqule announced a stock offering to take advantage of its surging share price and raise additional cash, shares kept on rising as investors remained enthusiastic about the biotech's pipeline potential.

Common denominators

You may have noticed several things in common for these five high-flying biotech stocks. They're all still small-cap stocks despite their big gains so far this year. They're all clinical-stage biotechs with no products yet on the market. And all five stocks soared as a result of positive pipeline developments.

Any or all of these stocks could keep the momentum going throughout the rest of 2019 and beyond, and all five biotechs have exciting pipeline candidates with significant potential. However, there's also another common denominator for these stocks: They're all risky. High risk is a trade-off for stocks that can deliver gains of 300% or more in only six months or so.