The next generation of cell therapies have focused in large part on the development of allogeneic — better known as ‘off-the-shelf — drugs that can cut manufacturing times and hopefully evade a patient’s immune system. One of the early players in that race has new data at #ASH21 that show deep responses but will also raise fresh concerns about these therapies’ durability.
Precision Biosciences’ PBCAR0191, a CD19-directed allogeneic CAR-T cell therapy, posted a complete response rate of 59% in 22 heavily pretreated patients with various forms of relapsed or refractory non-Hodgkin’s lymphoma and acute lymphocytic leukemia, six of whom had previously received an autologous CAR-T before dosing, the biotech said.
At a Nov. 16 data cutoff, PBCAR0191 spurred an overall response rate of 73% in that early Phase I/II cut, well in line with current-generation CAR-Ts, but durability concerns in this data set will likely raise eyebrows on Precision’s chance to upset current CAR-T and renew concerns about the field on the whole.
Among the 17 evaluable NHL patients in this study, most responders relapsed before hitting the six-month mark, shutting down the drug’s chances as a one-time infusion for most patients.
On the safety front, PBCAR0191 posted no serious cytokine release syndrome events and just one Grade 3 neurotoxicity side effect. There was one infectious death that investigators said was possibly related to treatment.
It’s a result that mirrors readouts from Precision’s nearest competitors Allogene and Crispr Therapeutics, both of which previously uncorked data for their own allogeneic CAR-Ts showing questions over durability. Precision did tout data in a small cohort of patients who had previously received an autologous CAR-T, saying their durability of response was longer than on that prior therapy, but it’s hard not to see PBCAR0191’s underwhelming results as an appetizer into Precision’s move into even more next-gen tech with a ‘stealth’ CAR-T dubbed PBCAR19B.
Precision uncorked very early Phase I data for that drug this weekend too, which uses gene editing to knock down beta-2 microglobulin, an MHC molecule that triggers a graft vs. host response, and insert an HLA-E transgene to evade rejection from patients’ natural killer cells.
A Phase I study in relapsed/refractory NHL is enrolling now, and Precision expects data by the middle of next year, CMO Alan List said in a statement.
Meanwhile, this weekend Precision also rolled out new data for its allogeneic BCMA-directed CAR-T candidate PBCAR269A showing the drug couldn’t top autologous CAR-T in terms of efficacy in a Phase I/IIa trial. Precision will now push a combination approach with this drug alongside nirogacestat, a gamma secretase inhibitor from SpringWorks Therapeutics, with data expected by the middle of next year.
Stéphane Bancel, Moderna CEO (Endpoints JPM20/Jeff Rumans)
Last fall, as their Covid-19 vaccine crossed the finish line, Moderna unveiled plans to take its newly proven mRNA platform and use it to effectively change how the world blocks humanity’s most persistent viral foes.
In addition to their pre-existing vaccine programs, executives announced new ones for flu, where vaccines have chronically underperformed, and HIV, which has eluded every inoculation effort over nearly 40 years. In flu, the other mRNA vaccine companies — BioNTech (with Pfizer), Translate Bio (under Sanofi), and CureVac (with GSK) — all had similar ambitions, hoping to make shots that were as high as 80% effective.
Helen Heslop, Center for Cell and Gene Therapy director
Tessa Therapeutics is doing CAR-T a bit differently. After reading out some positive — albeit early — results back in May showing their virus-specific T cells (VSTs) achieved three partial responses in patients with CD30-positive lymphomas, the company now says the fuller picture looks even brighter.
TT11x, Tessa’s ‘off the shelf’ CD30.CAR-modified Epstein-Barr virus-specific T-cell (EBVST) therapy, achieved a 77.8% overall response rate (7 of 9 patients) in a Phase I trial, the Singapore-based company announced at this year’s ASH conference. What’s more, four of those seven patients saw a complete response, Tessa said.
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The bulk of this week’s report is brought to you by Endpoints editors Nicole DeFeudis and Max Gelman, who are covering for me as I take a few days off after the big Women in Biopharma R&D event. We are really proud of both the special report and the live panel, which featured some great stories from trailblazing leaders and insights on gender diversity in biotech. Do check them out below if you haven’t had a chance.
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Stepping off the plane from Austin into this year’s American Society of Hematology annual meeting in Atlanta, I can’t help but feel some of the excitement and sense of intellectual ferment we used to feel around the biggest conferences of the year — but it’s undeniable this year is different.
No longer restricted to a wonky Internet platform, #ASH21 has adopted a live-virtual hybrid model, and I embraced the chance to return to my first live meeting in roughly two years — vaxxed, boosted and masked, of course. It’s good to be back, but I, like the rest of the world, am still adjusting to the new normal.
As a spate of researchers work diligently on next-gen CAR-T cell therapies, the big players in the current generation of those drugs are still angling for more market share. Getting to patients earlier is now the game plan, and Gilead’s Kite has uncorked some impressive data backing up its case in lymphoma.
Kite’s Yescarta (axicabtagene ciloleucel) cut the risk of disease progression, death or the need for additional therapy by a little more than 60% compared with standard of care in second-line patients with relapsed or refractory large B cell lymphoma, according to full data from the Phase III ZUMA-7 study revealed Saturday at #ASH21.
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Kicking off this weekend’s #ASH21, Gilead’s Kite and Bristol Myers Squibb have released competing data for their current-gen CAR-T drugs in second-line B cell lymphoma patients. It’s a heated contest to move these drugs into earlier lines of therapy, and Bristol Myers thinks these fuller data will keep the pressure on.
Bristol Myers’ Breyanzi (lisocabtagene maraleucel) cut the risk of disease progression, death and other events by 65% over standard of care in second-line relapsed or refractory LBCL patients, according to data from the Phase III TRANSFORM study presented Saturday.
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In a heated race with some of pharma’s biggest players, Roche’s Genentech is looking to drive a lead bispecific antibody program through the clinic against stubborn blood cancers. As the field watches closely, Roche is now trotting out data it thinks could earn its drug a first shot at the market.
Roche’s mosunetuzumab, a bispecific targeting the CD20 protein on the surface of tumors and the CD3 protein on T cells, posted a 60% complete response rate, according to data from nearly 100 patients with third-line-or-later follicular lymphoma in an open-label, single-arm Phase I/II study dubbed GO29781 presented Saturday at #ASH21.
House Speaker Nancy Pelosi (Jacquelyn Martin/AP Images)
Back in January 2019, the late House Oversight Committee chair Elijah Cummings kicked off a nearly 3-year-long drug pricing investigation that culminated today in a major new report detailing how prices for vital drugs have risen substantially since their launch, while calling on the Senate to pass a bill that will allow Medicare to negotiate some prices.
The committee’s investigation focused on 12 of the most expensive drugs for Medicare, showing massive price spikes that have accumulated over the years and made some drugs, like insulin, entirely unaffordable for some, to the point where some diabetics have had to ration their life-saving insulin, and some have died.
https://endpts.com/ash-another-off-the-shelf-cell-therapy-leader-shows-durability-issues-raising-renewed-concerns-about-emerging-field/
