As early as May 18, 2021, STAT Trials Pulse by AppliedXL began to surface irregularities in the progression of Aileron Therapeutic’s ALRN-6924 trial for chemoprotection in lung cancer, signaling a struggle for sufficient patients to determine significant efficacy. More than a year later, Aileron confirmed these red flags, terminating the trial and fueling a 41% drop in the company’s stock.
Background: Aileron Therapeutics first hit the biopharma scene with a new approach to drug delivery — the potential of stapled peptides offered an enhanced ability to effectively deliver drugs to a cell, and greatly expanded the possibility of therapeutic targets that could become “druggable.” With this unique first-in-class molecule came sufficient buzz – in 2017, Aileron raised $56 million in an IPO to fund the clinical development of their stapled peptide candidate, ALRN-6924.
Originally pitched as a p53-mediated tumor suppressor, ALRN-6924 began exploring both treatment of solid tumors, as well as selective chemoprotection. In July 2019, Aileron kicked off its first trial in chemoprotection in p53-mutated lung cancer, which, when tumor suppression results flailed, became the company’s sole program in development and their singular way forward.
Red flags: In mid-May 2021, a group of irregularities detected by STAT Trials Pulse surfaced red flags in the ALRN-6924 trial, serving as an early warning of potential problems within the trial.
On May 18, 2021, the trial completed enrollment with only 50% of the anticipated participants, cutting the patient count from an anticipated 120 to 60. Falling substantially below enrollment goals can change the validity of assumptions around efficacy and study design, impacting a trial’s ability to achieve target power and statistically reliable results. At the same time, the primary completion date of the trial was delayed substantially, moving from the previously-anticipated March 1, 2021, to June 1, 2022.
A few months later, on July 1, 2021, the trial again varied from regular trajectory, re-entering recruitment. Often, this serves as a signal that the sponsor is looking to increase the ability to detect a signal and may be struggling for statistical significance with its current patient pool.
The impact: One year later, on June 29, 2022, Aileron announced the disappointing results of an interim analysis, highlighting that ALRN-6924 was not performing better than placebo on the exploratory composite primary endpoint. The company shared that it planned to stop further enrollment and shift focus to its only remaining trial, exploring the impact of ALRN-6924 on chemoprotection in p53-mutated breast cancer. With this announcement, Aileron’s stock dropped by a drastic 41% in one day.
On October 11, 2022, Aileron officially terminated the trial on clinicaltrials.gov, specifically citing that they were unable to generate statistically significant results with the sample size of the trial.
The fallout: On February 21, 2023, Aileron announced the termination of the last trial for ALRN-6924, focused on p53-mutated breast cancer, sharing on clinicaltrials.gov a few days later that the first four patients enrolled experienced Grade 4 neutropenia and alopecia in their first cycle of treatment, failing both the primary endpoint and the main secondary endpoint.
This news sent the stock, which had been gradually falling since the news of the first trial’s failure, an additional 38% in one day. This marked the official endgame for Aileron’s sole drug candidate, prompting them to lay off most of the remaining staff and search for strategic options for an exit.
The bottom line: STAT Trials Pulse surfaced irregular signals that the ALRN-6924 trial may have been struggling for significance more than a year before Aileron announced results that echoed these warnings. Staying on top of red flags in critical drug pipelines can aid investors in getting ahead of market-moving announcements and allow biopharma professionals to strategize ahead of time.