Pascal Touchon, Atara CEO
After more than two decades in the clinic, Atara Biotherapeutics’ T cell therapy tabelecleucel is finally headed to the FDA — but not without a pivotal readout at this year’s ASH conference.
About half of patients responded to tab-cel, Atara’s candidate for Epstein-Barr virus-positive post-transplant lymphoproliferative disease (EBV+ PTLD), a rare complication that can occur after solid organ or hematopoietic stem cell transplant.
Patients who undergo a SOT or HCT are treated with drugs that suppress the immune system’s activity in order to avoid rejection of the transplant. However, immunosuppressive therapy leaves them at risk of infections like the Epstein-Barr virus, a common virus that typically doesn’t cause any issues in those with healthy immune systems. In some PTLD cases, abnormal white blood cells growing out of control can become infected with the Epstein-Barr virus.
It’s a small but desperate group of patients who contract EBV+ PTLD. While there are just several hundred new cases each year, HCT patients have a median survival of less than a month, and SOT patients live a median of just 4.1 months. The condition is often treated with a combination of chemotherapy and Genentech and Biogen’s Rituxan, but some patients don’t respond, or they have a recurrence.
All 38 patients in Atara’s Phase III ALLELE trial had failed on Rituxan, chemotherapy or both, receiving anywhere between one and five prior treatments. A total of 24 were SOT transplant patients, and 14 were HCT patients.
Overall response rate was 50% in both the SOT and HCT groups, according to Atara. Just over 26% of patients overall achieved a complete response, and just under 24% reached a partial response.
Eleven of the 19 responders saw a duration of response longer than six months, Atara said. Of the eight remaining responders, four patients experienced either disease progression or death, and four weren’t evaluable for a six-month response at the data cut. There were no treatment-related deaths, according to CMO AJ Joshi. Patients who responded to tab-cel survived longer than the non-responders, Joshi pointed out — with a one-year survival rate of 89.2% in the responder group versus 32.4% in the group that didn’t respond. Median overall survival wasn’t reached in the responder group.
‘This is (a) very aggressive, rapidly progressing disease once they fail’ rituximab and chemotherapy, Joshi told Endpoints News. ‘Some people even try such hard chemo that they need another transplant. So these are very aggressive options and the majority of time they don’t work.’
Tab-cel is designed to be an essentially chemo-free option, without the negative side effects of CAR-Ts. Its roots trace back to Richard O’Reilly’s lab at Memorial Sloan Kettering Cancer Center. The candidate makes use of EBV T cells from donors, which specifically target EBV-infected cells. These cells naturally have a low likelihood to harm normal tissues, and they’re able to persist in the body a long time, Atara says. Plus, there were no reports of side effects common to CAR-T therapies like graft-versus-host disease or cytokine release syndrome in the Phase III trial.
That’s not all Atara brought to ASH. The company also reported long-term results from Phase II and EAP trials, showing a median overall survival of 54.6 months. The overall complete response rate was 42.1%, and the partial response rate was 21.1%. Two-year survival rates for CR and PR patients were 86.2% and 86.5%, respectively.
Atara filed with the EMA in November, and is expecting a decision in the second half of 2022. An FDA submission should be coming in the first half of next year, Joshi said.
Sensor-based technology for clinical trial data collection represents the latest medical paradigm shift. There are more than 700 clinical studies involving wearable devices currently underway in the United States. A study from Intel IT projects their inclusion in clinical trials will surge to 70% by 2025.
Apps, biosensors and patient-centered technologies increase visibility of comprehensive patient data. Pharma leaders anticipate the benefits of wearables to include better data (58%), faster results (33%) and lower trial costs (10%).
The current generation of cell therapies has proven a game changer in terms of treating aggressive blood cancers, but the tech has its limitations. Novartis, one of the biggies in the current generation of these drugs, is now taking lessons learned from CAR-T Kymriah to supercharge a ‘second-generation’ of CAR-Ts putting superior cells into patients faster.
Novartis on Monday rolled out early Phase I data for a pair of autologous CAR-T cell therapies developed through the drugmaker’s T-Charge platform, a process designed to promote T cell ‘stemness’ — a measure of a cell’s ability to self-renew — by cutting manufacturing times and spurring cell proliferation primarily in patients’ lymph nodes.
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When Bristol Myers Squibb celebrated the approval of ozanimod — branded Zeposia — in ulcerative colitis earlier this year, the company touted the first gastrointestinal indication for an S1P receptor modulator.
Now Pfizer wants to give the pharma rival a run for its money.
Pfizer is dropping $6.7 billion to acquire Arena Pharmaceuticals, whose lead drug, etrasimod, targets the sphingosine 1-phosphate receptor.
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CAR-Ts targeting CD19 — like Yescarta, Kymriah and the recently approved Breyanzi — have shifted the paradigm for the treatment of B cell lymphoma, according to Sairah Ahmed, a longtime researcher in the field. Now, as principal investigator, she’s leading efforts to see if Tessa Therapeutics’ CD30-targeting CAR-T can do the same for patients with classical Hodgkin lymphoma (cHL).
More than half of the patients who took Tessa’s candidate TT11 in the pilot stage of a Phase II study saw their cancer disappear, the company said at this year’s ASH conference. Of 15 heavily pre-treated patients with relapsed or refractory CD30-positive cHL, 11 saw disease control at the data cut off, including eight complete responses, two partial responses and one case of stable disease, according to researchers.
Frank Neumann, Kite global head of clinical development
With the cell therapy field largely pivoting to the next generation of those drugs, established players like Gilead’s Kite and Bristol Myers Squibb are still carving away at new routes into earlier lines of care. This weekend, Kite churned out more data for its CAR-T Yescarta in first-line lymphoma patients as part of a hopeful push for a greater market share.
In updated results from the Phase II ZUMA-12 study, Yescarta posted a 78% complete response rate among 37 patients with high-risk large B cell lymphoma at a median follow-up of just shy of 16 months, the drugmakers said Monday at #ASH21.
Precision CMO Alan List (Diane Bondareff/AP Images for Moffitt Cancer Center)
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.
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.
Roberto Bellini, Bellus Health CEO
Do investors want the good news, or the bad news first? Bellus went with the good news, sharing that its chronic cough contender hit the primary endpoint in a Phase IIb trial, lining it up for a Phase III study in the second half of next year where it could pose stiff competition for Merck.
Amidst all the commotion, the Canadian biotech also revealed that the same candidate flunked a proof-of-concept trial in atopic dermatitis, and the company will now steer the program away from pruritic conditions.
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Li Ning, Junshi Biosciences CEO
Four months after its first upbeat interim analysis, Shanghai’s Junshi Biosciences and California biotech Coherus BioSciences are touting a statistically significant improvement in overall survival for patients treated with toripalimab plus chemotherapy as a treatment for advanced squamous or non-squamous NSCLC.
The drug, an anti-PD-1 mAb already approved in China as Tuoyi, previously beat placebo as a first-line treatment when combined with chemotherapy. Among 465 advanced NSCLC patients who have never received therapy (both squamous and nonsquamous), investigators observed a ‘significant improvement in progression-free survival.’
https://endpts.com/ash-with-phiii-data-in-hand-atara-eyes-a-submission-to-treat-a-small-but-desperate-group-of-transplant-patients/
