Arcellx has shared several data cuts on anito-cel, a CAR-T being developed with Gilead Sciences' Kite Pharma to treat relapsed or refractory multiple myeloma (RRMM). After seeing the data, analysts underscored the therapy’s best-in-class potential compared to Johnson & Johnson and Legend Biotech's FDA-approved treatment Carvykti.
Abstract data from early and midstage trials assessing anitocabtagene autoleucel (anito-cel) were published today ahead of the 66th American Society of Hematology (ASH) annual meeting, which will take place from Dec. 7-10 in San Diego.
First up is iMMagine-1, a pivotal phase 2 trial evaluating the BCMA-directed CAR-T among patients who'd received a median four lines of prior treatment. Even more recent results from the study will be shared during ASH, according to Arcellx.
With a cutoff of June 1, this data slice featured 58 patients receiving anito-cel infusion at a median follow-up of 10.3 months. The overall response rate (ORR) was 95% (55/58) and the complete response/stringent complete response (CR/sCR) rate was 62% (36/58), according to the Nov. 5 release.
The estimated six-month progression-free survival (PFS) and overall survival (OS) rates were 90% and 95%, respectively. Median PFS (mPFS) and median OS were not yet reached.
While cross-trial efficacy comparisons are challenging to make, analysts at both Evercore ISI and William Blair said the data appear comparable to J&J and Legend’s Carvykti, the only BCMA-targeted treatment currently approved for RRMM patients who have received at least one previous line of therapy.
The William Blair team highlighted the CR rate in iMMagine-1, noting that the rate is trending higher than what was seen in Legend’s phase 1b/2 CARTITUDE-1 study. This suggests anito-cel could lead to deeper responses, according to a note from William Blair analyst Sami Corwin, Ph.D.
BCMA CAR-T responses can potentially deepen over time, so the CR rate may therefore be higher in Arcellx’s ASH presentation, Corwin added.
On the safety side, no delayed neurotoxicities were reported. Nervous system toxicity can occur after CAR-T therapy administration and include parkinsonism, cranial nerve palsies and Guillain-Barré syndrome. No delayed cases of any of these conditions have been observed yet across both the phase 1 and 2 studies, according to Arcellx.
The lack of any delayed neurotoxicities in more than 140 patients is a “significant positive for anito-cel indicating a clearly differentiated safety profile,” according to Evercore analysts.
Three fatal adverse events were reported. The patient deaths—both related and unrelated to anito-cel—were due to retroperitoneal hemorrhage, cytokine release syndrome (CRS) and fungal infection, according to Arcellx.
Last year, the FDA slapped a brief hold on the trial in the wake of a patient death. At the time, Arcellx said it believed a contributing factor in the fatality had been “limitations on bridging therapy,” a term for the treatments given in the period between the T cells being removed from a patient’s body and the CAR-T drug being infused.
The biotech later shared that the patient had in fact become ineligible for treatment under the trial protocol prior to receiving the anti-BCMA therapy. “Subsequently, the patient was managed in a manner that conflicted with the trial protocol,” Arcellx said at the time.
To allow the phase 2 study to continue, the FDA signed off on an updated trial protocol but agreed to an expanded range of bridging therapies.
The new safety findings include data on CRS, a systemic inflammatory response syndrome that can be triggered by CAR-T therapy. In total, 84% (49/58) of treated patients experienced a CRS event, with 2% (1/58) of patients experiencing a grade 3 event or higher.
Analysts are bullish on the therapy’s safety, with William Blair's Corwin writing that “anito-cel has demonstrated clear safety benefits compared to Carvykti,” citing lower CRS and death rates attributable to adverse events.
Additionally, the analyst believes anito-cel’s risk/benefit profile “could not only make it a more appealing therapeutic option, but it could be more amenable for use in the outpatient treatment setting.”
Arcellx also shared phase 1 data assessing 38 patients with RRMM, reporting a 100% ORR and a 79% CR/sCR rate at a median follow-up of 38.1 months. A 30.2-month median PFS was recorded, with the median OS not reached. The PFS is an improvement compared to an estimated mPFS of 28 months reported last year.
Arcellx will be hosting a live webcast to discuss the data findings Monday, Dec. 9.
Back in 2022, Gilead inked a deal with Arcellx to co-develop and co-commercialize anito-cel in RRMM. A year later, the Big Pharma expanded the deal to include another BCMA CAR-T candidate and revise the existing collaboration to cover lymphomas.
Now, the partners have moved the Kite-manufactured cell therapy into a phase 3 trial dubbed iMMagine-3. The pivotal trial is designed to enroll 450 RRMM patients who have received one to three prior lines of therapy.
The late-stage study has already launched, with 130 trial sites set up across the world and the first patient dosed.
Anito-cel has snagged fast track, orphan and regenerative medicine advanced therapy tags from the FDA.
Despite analysts’ bullish takes, Arcellx’s stockholders have failed to show the same enthusiasm, with share prices remaining level at $86.70 as of 2 p.m. ET today, compared to $86.44 at market close yesterday.
“We believe the stock’s weakness on the data is overblown and may be stemming from the report of one patient death due to CRS or the updated mPFS reported in the phase 1 trial,” William Blair's Corwin wrote. However, the analyst pointed to the fact that CRS-related deaths aren’t unique to anito-cel, and the patient population enrolled in the phase 1 study had a higher disease burden than the patients in Legend’s CARTITUDE-1 study, which recorded a mPFS result of 34.9 months.
“Overall, we are inclined to say anito-cel is a potentially best-in-class program,” Corwin continued. “We remain confident in the long-term therapeutic potential of anito-cel and continue to view the Kite collaboration as a significant positive for the company, both in terms of securing a strategic partner to launch anito-cel in the competitive multiple myeloma market and the economic terms of the deal.”