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CRISPR Therapeutics reports remissions, one death in cancer cell therapy study

An experimental, “off-the-shelf” cell therapy developed by CRISPR Therapeutics led to complete remissions in four of 11 patients with lymphoma who were treated in an early-stage trial, the Switzerland-based biotech reported Wednesday.However, one of those patients, the only one who received the highest dose of the treatment, died 52 days after receiving an infusion, the company said. The biotech will pause enrollment of patients into that high dose arm of the study.

CRISPR, along with companies like Allogene Therapeutics and Precision Biosciences, are racing to develop an off-the-shelf cell therapy for lymphoma, aiming to improve on patient-derived cell treatments like Novartis’ Kymriah and Gilead’s Yescarta. Recent data for Allogene’s therapy showed treatment led to partial or complete remissions in nearly two-thirds of patients and, while some experienced severe side effects, none died.

The advent of CAR-T cell therapies was a step forward for advanced blood cancer patients who had progressed following treatment with other, more conventional drugs.

But CAR-T cell therapies don’t come cheap, with treatment costing in the hundreds of thousands of dollars. And, apart from their hefty price tag, the therapies are limited by the process used to create them. T cells must be withdrawn from patients, shipped to a laboratory where they are re-engineered to target cancerous blood cells and then re-infused back into the same patient. The process can take several weeks and isn’t always successful.

CRISPR Therapeutics, Allogene and Precision aim to improve on this with CAR-T therapies derived from the T cells of healthy donors, which would eliminate the wait time as well as the risk of manufacturing failure. CRISPR Therapeutics uses CRISPR/cas9 gene editing to engineer a tumor-seeking chimeric antigen receptor, or CAR, onto the T cells, making an experimental product it calls CTX110.

The Phase 1 trial of CTX110 is designed to find the best dose to take into later-stage trials that could prove the treatment’s benefit and, possibly, be used to seek approval.

After one month, no tumor responses were observed in the three patients given the lowest dose of 30 million cells. One of three treated with a dose of 100 million cells went into a complete remission, while two of four given a 300 million cell-dose also experienced complete remissions.The one patient who received the highest dose of 600 million cells went into remission, too, but died a month and a half later.

That patient first experienced a drop in white blood cell counts beginning 26 days after infusion. After hospitalization, doctors found the patient had encephalitis related to reactivation of a virus that can occur as a result of transplant-related immunosuppression, which all of the patients in this trial underwent before receiving CTX110.

The safety profile in the lower doses appeared better. No patients experienced graft-vs-host disease, a potential risk of allogeneic transplants. Cytokine release syndrome, an inflammatory response common with CAR-T therapies, occurred in three patients in patients receiving these lower doses, but was judged to be of moderate severity and later resolved.

In data presented earlier this year, Allogene’s treatment led to responses in 12 of 19 patients and complete remissions in seven. By comparison, data from the study that supported Kymriah’s Food and Drug Administration approval in adults, the Novartis cell therapy spurred remissions in half of patients and complete remission in about one-third.

In a note to clients, Stifel analyst Benjamin Burnett wrote that the 600 million cells used as a high dose by CRISPR Therapeutics was much greater than the 360 million cells Allogene used as the high dose in its early stage trial.

Following announcement of data Wednesday, shares in CRISPR Therapeutics fell by more than 10%.