- Allogene Therapeutics, a company that's been at the forefront of developing "off-the-shelf" cell therapies for cancer, has disclosed plans to run two pivotal trials for its leading lymphoma treatment after being cleared by U.S. regulators last month to resume human testing.
- Allogene remains "on track" to run the first of the two studies of the drug, known as ALLO-501A, by the middle of the year, CEO David Chang said on an earnings call Wednesday afternoon. But the company also revealed plans to run a second study testing the regimen it uses to prepare patients for treatment with ALLO-501A.
- Chang didn't detail the design of either trial because of continuing discussions with the Food and Drug Administration and the "competitive nature of the field," which now includes multiple programs either in or nearing pivotal testing. They'll be disclosed when the studies start, according to company executives.
Allogene, once the leading company developing more convenient alternatives to CAR-T cell therapy, now is working to keep pace.
Plans to start a pivotal study of ALLO-501 by the end of 2021 were set back last year when the FDA halted all of Allogene's trials because of the unexpected finding of a "chromosomal abnormality" in a treated patient.
Allogene was cleared in January to restart testing after conducting an investigation that exonerated its treatment. However, the delay allowed CRISPR Therapeutics and its similar, rival program to move ahead. Advanced testing of CRISPR's treatment began this month.
Allogene also is facing a more crowded field than when former Kite Pharma executives launched the company in 2018 with $300 million from Pfizer and other venture capital backers.
Developers of "off-the-shelf" T-cell-based therapies like Allogene now have been joined by an emerging group of companies advancing treatments that instead use natural killer cells. The bar for success also has risen, as personalized cell therapies for lymphomas, leukemias and multiple myeloma have proven powerfully effective and long-lasting. Some are moving toward use in earlier lines of care.
CAR-T developers are working on accelerating manufacturing as well, an effort that could reduce the convenience advantage for off-the-shelf therapies.
Moreover, the prospects for Allogene's and CRISPR's treatments have diminished amid questions on their durability and effectiveness compared to CAR-T. For example, an early look last year by Allogene at re-dosing patients to strengthen the effects of ALLO-501A underwhelmed some Wall Street analysts. Further results are expected this year.
"At this point we don't have enough conviction to build a positive thesis" around [Allogene's] lead program, Stifel analyst Benjamin Burnett wrote Thursday, adding that there is "meaningful competitive risk" to Allogene's position. Allogene shares, once worth more than $50 apiece in May 2020, now trade at less than $9 after falling in Thursday morning trading.
The company's path forward will involve two trials instead of one because the FDA requires that the benefits and risks "be shown and demonstrated for each one of the components" of Allogene's treatments before approval, Chang said. Allogene will run separate tests on ALLO-501A as well as an experimental, immunosuppressive antibody drug, ALLO-647, the company is using to prep patients for treatment.
While specifics weren't disclosed, the study of ALLO-501A won't have a control arm, much like the tests that supported approvals of other cell therapies for late-line lymphoma treatment. Meanwhile, the ALLO-647 study will compare that drug alongside a chemotherapy combination to the chemo regimen alone. Regulators likely will be watching to see whether the drug's addition leads to more viral infections, a concern flagged by outside experts.
The results of the latter study could have implications beyond Allogene's lead program. ALLO-647 is involved in some of its other experimental treatments including a multiple myeloma drug in early testing.
"Certainly, there is a possibility of study failure," Chang said, but "we're pretty confident that [ALLO-647] leads to better outcomes."