- Allogene Therapeutics reported the first glimpse of clinical data for an experimental "off the shelf" cell therapy it has been developing for multiple myeloma, one of several similar treatments biotechs are advancing for the persistent and deadly blood cancer.
- In early results published ahead of the year's largest meeting on blood diseases, study investigators reported that five of 15 evaluable patients in a Phase 1 trial responded to treatment after a median of two months of follow-up, with the best response rate (60%) coming at the highest tested dose. Allogene also reported no instances of graft-versus-host disease, a key worry with a treatment that infuses patients with foreign cells.
- Still, one patient died shortly after treatment, an event investigators considered related to disease progression and a conditioning regimen the company uses to prep patients for their infusion with ALLO-715. That regimen includes an experimental antibody drug, ALLO-647, meant to boost the effectiveness of the company's cell therapies. Allogene's shares fell 13% on Wednesday.
Within the next couple years, the fast-moving treatment landscape for multiple myeloma could change with the approval of potentially two cell therapies for the deadly cancer.
Those treatments, from Bristol Myers Squibb and Johnson & Johnson, could present new options for patients whose multiple myeloma keeps coming back. The so-called CAR-T cell therapies they're developing re-engineer patients' own immune systems to attack tumor cells, specifically those that make a protein called BCMA. Each has shown promise in clinical testing. Bristol's candidate, being developed with Bluebird Bio, is currently under FDA review. J&J's, licensed from Legend Biotech, could soon follow before the end of 2020.
But before these treatments get to market, they're already facing the prospect of new competition from a group of companies developing allogeneic, or "off the shelf" approaches. Unlike the therapies from Bristol and J&J, allogeneic treatments modify cells from donors, an approach that could make CAR-T cell therapy — which has struggled commercially and requires a multi-week manufacturing and delivery process — more accessible. Allogene, CRISPR Therapeutics, Precision Biosciences and Poseida Therapeutics each have one in or close to their first human trials.
But allogeneic treatments, despite some early, encouraging results in lymphoma, have big questions to answer. It's unclear whether they'll be as effective and durable, for instance, as their autologous rivals. And a patient's immune system could reject a treatment based on foreign cells.
Clinical data disclosed by Allogene Wednesday are the first of many to come in multiple myeloma. Precision Bio, for instance, began enrolling patients in a Phase 1 study in June. CRISPR could produce the first results for its off-the-shelf candidate next year.
The bar being set by CAR-T in myeloma, however, is high. Some 73% of heavily pretreated multiple myeloma patients responded to Bristol's treatment, ide-cel, in the Phase 2 study leading to its approval filing. Though it's difficult to compare drugs across trials, the response rate for J&J's rival has been even better so far.
The results Allogene is presenting don't meet that bar, but it should be noted that they come from an early trial the company is using to find the best dose and conditioning regimen to carry into further testing. Overall, five of 15 (33%) evaluable patients who had failed a median of five treatments had ongoing responses to ALLO-715 after two months of follow-up. Allogene noted that the results were better — three of five responses, including one patient with no trace of cancer — among those who got the highest dose tested.
The company didn't see any instances of graft-vs-host disease or neurological problems, and only mild to moderate cases of cytokine release syndrome — a common and potentially dangerous immune reaction to CAR-T treatment.
But four patients contracted potentially serious infections. One of them died, which study investigators blamed on "progressive disease" and one of the two conditioning regimens Allogene is testing. That regimen includes an antibody drug known as ALLO-647 that Allogene is also utilizing in testing of its experimental lymphoma treatment.
While acknowledging the "mixed" results, RBC Capital Markets analyst Issa Luca noted that many patients likely received "sub-therapeutic" doses of ALLO-715 and that patients have died in trials of Bluebird and J&J's treatments as well. Allogene also hasn't yet reported on those who got a high dose of ALLO-647, which appears to have helped boost results to the lymphoma cell therapy, known as ALLO-501, Luca wrote.
Allogene will present more detailed results, including data from five additional patients, at the American Society of Hematology's virtual meeting next month. The biotech noted that it is still enrolling patients at the higher doses.