Ayala Pharmaceuticals’ AL102 Granted Orphan Drug Designation by FDA


Ayala Pharmaceuticals’ AL102 is a gamma secretase inhibitor being studied to treat patients with desmoid tumors.

The FDA has granted orphan drug designation to Ayala Pharmaceuticals’ AL102, a gamma secretase inhibitor (GSI) under evaluation for patients with desmoid tumors.1 AL102, a small molecule DSI, has been developed to inhibit NOTCH gene targets by stopping the final cleavage step by the GS required for the activation of NOTCH.

Image credit: wladimir1804 | stock.adobe.com

Image credit: wladimir1804 | stock.adobe.com

“Receiving FDA orphan drug status for AL102 underscores the significant unmet need for novel treatment options for people living with desmoid tumors,” said Kenneth A. Berlin, president and chief executive officer of Ayala Pharmaceuticals, in a statement. “We look forward to continuing to work closely with regulators, clinical investigators, patients, and their families to advance this potentially important medicine and make it available to those who may benefit from it.”

Desmoid tumors, or aggressive fibromatosis, are noncancerous growths that develop in connective tissue, most frequently found in the abdomen, arms, and legs. Some desmoid tumors develop slowly without the need for immediate treatment, whereas others grow quickly and are treated with surgery, radiation therapy, chemotherapy, or other treatments.2

Interestingly, because desmoid tumors don't spread to other parts of the body, they aren't considered a cancer. However, the tumors can grow aggressively and act similar to other cancers by growing into nearby structures and organs.

Risk factors for desmoid tumors include young adult age, as they frequently occur in younger adults in their 20s and 30s. Other risk factors include having a genetic syndrome that causes colon polyps; pregnancy, as they may develop during or soon after pregnancy; and injury or surgery.

AL102 is currently under evaluation in the phase 2/3 RINGSIDE trial (NCT04871282) among patients with progressing desmoid tumors.

Data from RINGSIDE were presented at the 2023 ASCO Annual Meeting, which showed AL102 was well tolerated across all dose arms. Researchers did not find any complete responses; however the drug did produce partial responses across all doses.3

Patients administered 1.2 mg of AL102 once daily experienced an overall response rate (ORR) of 50%, with 50% of patients showing stable disease (SD). Median time to response was 6.7 months. Patients administered 4 mg of AL102 twice weekly showed an ORR of 23.1% and an SD rate of 76.9%, with median TTR at 9.8 months. Patients administered 2 mg twice per week had an ORR of 45.5%, an SD rate of 36.4%, and a progressive disease rate of 18.1%, with median TTR at 9.1 months.

Approximately 71% of adverse effects (AEs) observed in the trial were grade 1 and approximately 25% were grade 2, with no grade 4 or 5 AEs observed. However, 14% of patients experienced serious AEs, but these were not found to be related to AL102, according to the investigators.

AEs caused treatment discontinuation in 14% of patients, which occurred within the first 3 months of treatment. Grade 2 AEs that led to discontinuation included rash, keratitis, stomatitis, diarrhea, and elevated alanine aminotransferase.

Enrollment is ongoing for the phase 3 portion of the RINGSIDE trial.


  1. Ayala Pharmaceuticals announces AL102 receives orphan drug designation for desmoid tumors. News release. Ayala Pharmaceuticals. November 6, 2023. Accessed November 6, 2023. https://ir.ayalapharma.com/news-releases/news-release-details/ayala-pharmaceuticals-announces-al102-receives-orphan-drug
  2. Mayo Clinic. Desmoid Tumors: Symptoms & Causes. [Internet]. Available from: https://www.mayoclinic.org/diseases-conditions/desmoid-tumors/symptoms-causes/syc-20355083#:~:text=Desmoid%20tumors%20are%20noncancerous%20growths,don't%20require%20immediate%20treatment. Accessed November 7, 2023.
  3. Gounder MM, Jones RL, Chugh R, et al. RINGSIDE phase 2/3 trial of AL102 for treatment of desmoid tumors (DT): Phase 2 results. J Clin Oncol. 2023;41(suppl 16):11515. doi:10.1200/JCO.2023.41.16_suppl.11515
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