Understanding the FDA Approval Process for ALK-Positive Drugs: When Will NVL-655 Be Available?
For those living with ALK-positive lung cancer, the search for new treatments feels like a race against time. When current therapies lose effectiveness, patients and their loved ones are left waiting for the next breakthrough. NVL-655, an experimental ALK inhibitor, is one of the most anticipated new treatments, designed specifically to overcome resistance mutations that develop after other ALK-targeted therapies.
One of the most pressing questions in our support group is: When will NVL-655 be available? The drug has shown promising early results in Phase 2 clinical trials, but regulatory approval takes time. Understanding the FDA approval process in the U.S. can help us anticipate when NVL-655 might finally reach patients in need.
The U.S. FDA Approval Process for ALK-Positive TKI Inhibitors
Breakthrough Therapy Designation
This designation is granted to drugs that show early clinical trial evidence of significant improvement over existing treatments. It speeds up development by providing additional FDA guidance and support.
Expanded Access (Compassionate Use)
When no other treatment options exist, patients with serious or life-threatening conditions may qualify to receive the investigational drugs outside of clinical trials.
Priority Review (Final Review Phase)
This status shortens the FDA’s standard review time from 10 months to 6 months for drugs that offer notable improvements in treatment outcomes.
Accelerated FDA Approval
The FDA may grant early approval for a drug based on preliminary clinical trial data, such as tumor shrinkage or biomarker response, rather than waiting for full trial results. This expedited pathway allows the drug to be marketed and made available to patients. However, the manufacturer must continue to provide comprehensive trial data to confirm the drug’s long-term safety and effectiveness for full FDA approval.
Other ALK Inhibitors as Examples of the Approval Process
Lorlatinib’s journey from Breakthrough Therapy Designation to Accelerated FDA Approval took 19 months (first-line approval came later, after an additional two and a half years). In comparison, the approval process for second-line Alectinib was quicker, taking just 14 months. All current ALK TKIs had the benefit of Breakthrough Therapy Designation, Priority Review, and Accelerated Approval to bring the drugs to patients as rapidly as possible.
Where Does NVL-655 Stand in the Approval Process?
For NVL-655 in later-line settings, the timeline is beginning to take shape:
Breakthrough Therapy Designation was granted for second line treatment on May 16, 2024.
Expanded Access was announced on February 19, 2025. https://nuvalent.com/expanded-access-policy/
Neladalkib Expanded Access CT.gov link: provides more detail concerning the inclusion and exclusion criteria. However, it is important that patients speak with their doctors regarding individual eligibility.
Projected FDA Approval is hoped to be in 2026, after completing the Priority Review and Accelerated Approval stages.
The Bottom Line
The FDA approval process for ALK inhibitors can feel slow, but it is designed to ensure safety and effectiveness while expediting access for patients in need. Based on past approvals, NVL-655 is on track for approval in 2026. In the meantime, Expanded Access may provide an option for some patients who have exhausted other treatments. Stay tuned for updates as more information becomes available!
Clinical Trials Currently Recruiting for ALK-positive Cancers.
General Information About Clinical Trials
ALK Positive, in collaboration with Wayne State University, is seeking more information about the experiences of those diagnosed with ALK-positive lung cancer. They have created a survey with many points of interest, including the experiences of those who have participated in clinical trials. The survey is confidential and approved by a research governing body. To complete the survey, please click here: ALK-positive Lung Cancer Registry and Survey
As of January 2025, there are at least 40 clinical trials that are recruiting specifically for people with ALK-positive lung cancer. Many of these trials have multiple sites worldwide. Since ALK-positive lung cancer is a rare disease, it is difficult for any one oncologist to be aware of all the trials available. You can advocate for yourself and find a clinical trial that may be a good fit for you at any juncture in treatment.
*The ALK Positive Clinical Trials Spreadsheet was developed by the ALK Positive Medical Committee. The database is updated monthly. Disclaimer: these trials have been consolidated by volunteers and should not be considered exhaustive. Listing of these trials is not an endorsement, and ALK Positive does not recommend one trial over another. Please talk with your doctor about these or any trials you are interested in.
By Ellee Urban with assistance from ChatGPT.