Four groundbreaking clinical studies worth your attention

By Samar Mahmoud, PhD | Medically reviewed by Kristen Fuller, MD
Published September 8, 2022

Key Takeaways

  • There are over 400,000 clinical trials taking place worldwide at the current time.

  • Clinical trials to watch out for include tests of first-in-class drugs targeting pulmonary arterial hypertension, as well as trials showing the potential of CRISPR gene editing in humans.

  • The first drug to target KRAS mutants has shown promise for the treatment of patients with advanced non-small cell lung cancer.

Clinical trials provide opportunities to learn more about disease states and ultimately change the face of medicine. However, with 425,236 clinical trials taking place worldwide as of August 18, 2022, according to, it becomes challenging to determine which studies are worth following.[]

Here are four groundbreaking clinical trials that have the potential to shape medicine beyond 2022.


Pulmonary arterial hypertension is a rare but potentially fatal type of high blood pressure that occurs in the lungs. While current treatments slow down disease progression, the 5-year survival rate remains approximately 60%.[]

Sotatercept is a first-in-class fusion protein that led to a decrease in pulmonary vascular resistance in patients receiving background therapy for pulmonary arterial hypertension. These promising results were from a 24-week multicenter trial.[]

Sotatercept was originally the result of a partnership between Celgene and Accerleon.

However, Merck acquired Acceleron due to sotatercept’s promise as a first-in-class treatment for pulmonary arterial hypertension. Merck is expected to report results from STELLAR, a phase 3 trial of sotatercept, by the end of 2022. If successful, Merck hopes sotatercept will replace lost revenue from its cancer drug Keytruda, which is scheduled to be pulled in 2028.

CodeBreak 200

For 40 years, pharmaceutical companies failed to design drugs that could bind to proteins produced by mutant KRAS, a gene commonly found mutated in cancers of the lung, colon, and pancreas. In addition, patients with advanced non-small cell lung cancer with KRAS G12C mutations who are on second- and third-line treatments have poor survival outcomes.

To fill this gap, Amgen developed sotorasib, the first KRAS G12C inhibitor. It showed progression-free survival (6.8 months) in a phase 2 study. The phase 2 trial also showed that 37.1% of patients responded to sotorasib treatment with a 10-month median duration of response.

"Patients with advanced non-small cell lung cancer who have failed first-line treatment face extremely poor outcomes with limited treatment options available to them, and Amgen has been committed to changing that," said David M. Reese, MD, executive vice president of Research and Development at Amgen, in a press release.[]

"Targeting KRAS has been a 40-year quest by scientists and researchers around the world, and we are extremely pleased that sotorasib has successfully demonstrated rapid, deep, and durable responses in this registrational phase 2 study that was conducted in record time,” Dr. Reese continued.

"We are proud that sotorasib may potentially become the first approved targeted therapy for these patients."

David M. Reese, MD

CodeBreak 200—a global phase 3 randomized study in which sotorasib will be compared against docetaxel, a standard chemotherapeutic agent for the treatment of KRAS-mutated lung cancers—is currently underway.


Historically, it‘s been challenging for pharmaceutical companies to develop novel therapeutics for psychiatric disorders. For example, potential schizophrenia drugs from Acadia Pharmaceuticals and Neurocrine Biosciences have failed to make it to the market in recent years. Despite this, the FDA approved two new schizophrenia medications in 2019 and 2021.

KarXT, a drug being developed by Karuna Therapeutics, led to significant reductions in the severity of schizophrenia symptoms in study participants compared with a placebo.

The phase 2 study found that KarXT was also well-tolerated, which was critical since one of the drug’s components led to concerning side effects in a previous, unrelated clinical trial.

Karuna is currently running two larger clinical trials. The first trial, EMERGENT-2, is expected to report results by the end of September 2022, and has enrolled approximately 250 adult patients with schizophrenia.


Transthyretin amyloidosis is a life-threatening condition characterized by the buildup of misfolded transthyretin (TTR) protein in tissues, such as in the nerves and the heart.

NTLA-2001 is a gene-editing drug that has been developed by Intellia Therapeutics to treat transthyretin amyloidosis by decreasing the concentration of TTR in serum. This drug is based on the CRISPR-Cas9 system, and is composed of a lipid nanoparticle that encapsulates messenger RNA for Cas9 protein and a guide RNA that targets TTR.[]

A small study of six patients with transthyretin amyloidosis who received NTLA-2001 showed decreased TTR serum levels and only mild adverse events.

This study served as the first proof that CRISPR-based gene editing could potentially be successful inside humans.

Phase 1 studies are ongoing to evaluate the pharmacokinetics, pharmacodynamics, safety, and tolerability of NTLA-2001 in patients with hereditary transthyretin amyloidosis with polyneuropathy and transthyretin amyloidosis-related cardiomyopathy.

What this means for you

There are over 400,000 clinical trials underway as of August 2022. These four clinical studies have the potential to change the face of medicine. They range from a study with a first-in-class fusion protein for the treatment of pulmonary arterial hypertension to the first KRAS G12C inhibitor to show promise after 4 decades of failed attempts to design drugs that target KRAS mutants.

Read Next: These four phase 3 trials offer encouraging results
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