EU Fast-Track Fail For Another BMS CAR-T Cell Therapy

Bristol Myers Squibb says it is common for cell and gene therapies to revert to the standard timetable as ide-cel follows liso-cel in losing its accelerated assessment status at the European Medicines Agency. Separately, the company has discontinued development of orva-cel, a CAR-T cell therapy that was earlier in the development pipeline.

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Fast-track review can shorten the time to market for new drugs

A second CAR-T cell therapy from Bristol Myers Squibb that is under review at the European Medicines Agency has lost its fast-track status.

Lisocabtagene maraleucel (liso-cel) reverted to standard review timelines a couple of months ago and now idecabtagene vicleucel (ide-cel), from BMS and bluebird bio, has followed suit. The latest list of marketing authorization applications (MAAs) going through the EU centralized drug evaluation procedure at the EMA shows that ide-cel, a potential treatment for adults with heavily pre-treated multiple myeloma, is no longer being reviewed under the accelerated assessment mechanism.

Ide-cel targets the B-cell maturation antigen (BCMA). In related news, BMS has discontinued development of another investigational anti-BCMA CAR-T cell therapy, orvacabtagene autoleucel (orva-cel). Also like ide-cel, orva-cel was in development for heavily pretreated multiple myeloma patients but it was at an earlier stage in the company's R&D pipeline.*

Fast-track review can cut a few months off the approximately 12 months it takes to review an application under the standard EU centralized drug evaluation procedure timelines.

As was the case with liso-cel, BMS declined to give a precise reason for the switch relating to ide-cel. The company again noted that such developments – in relation to cell and gene therapies – are far from unusual. (Also see "Fast-Track Loss In EU For Celgene’s CAR-T Cell Therapy" - Pink Sheet, 18 Dec, 2020.) It told the Pink Sheet: “Similar to other cell and gene therapies undergoing regulatory review in Europe, it is common for the procedure to revert to a standard timetable. We continue to work closely with the EMA to support its review and bring ide-cel to patients in the European Union as quickly as possible.”

BMS noted that its MAA for ide-cel (bb2121) was validated by the EMA in May 2020. It added: “We have submitted a robust dossier as part of our MAA, including results from the pivotal Phase 2 KarMMa study, and we are confident in the potential of ide-cel as an important and novel therapeutic option for patients battling this aggressive blood cancer.” 

“We cannot comment on the expected timing for the [EMA's] Committee for Medicinal Products for Human Use (CHMP) review of ide-cel," the company said.

EU & US Action For Both Products

Ide-cel and liso-cel are among several gene therapies expected to be approved in the EU in 2021.  (Also see "EU Gene Therapy Submissions, Approvals Expected To Pick Up In 2021" - Pink Sheet, 4 Jan, 2021.)

The EU review of liso-cel, which has just been approved after some delay in the US under the brand name Breyanzi, began in July 2020. Breyanzi was approved in the US for the treatment of adult patients with certain types of large B-cell lymphoma who have not responded to, or who have relapsed after, at least two other types of systemic treatment.  (Also see "BMS’ Breyanzi Beats COVID-19 Constraints, Emerges As First RMAT Approval" - Pink Sheet, 5 Feb, 2021.)  

Ide-cel is also under review in the US, where there is keen interest as to whether the currently expected date of 27 March for a regulatory decision by the Food and Drug Administration will be met. (Also see "Breyanzi Is Third To Market, But BMS’s First CAR-T Therapy Priced Above Competitors" - Scrip, 8 Feb, 2021.)

MAAs Under Accelerated Assessment

The EMA identifies four MAAs as currently being reviewed under the accelerated assessment mechanism. Its latest list of MAAs under review is dated 4 February and was published on 10 February.

 The products are as follows:

• Regeneron Pharmaceuticals' evinacumab

• elivaldogene autotemcel (eli-cel) from bluebird bio

• Albireo Pharma’s odevixibat

• risdiplam, from Roche/PTC Therapeutics.

Orva-Cel

In relation to the discontinuation of orva-cel, BMS said the following in a statement: "We have made the decision to not pursue further development of [orva-cel], based on the latest data available and rapidly evolving treatment landscape. Of note, no new safety signals have been observed that led to this decision. With a wide range of diverse mechanisms and modalities – including multiple BCMA-directed agents – Bristol Myers Squibb has the broadest portfolio in multiple myeloma and remains dedicated to bringing forward meaningful new options for patients in need.

We express our sincere thanks and gratitude to the patients and investigators who have participated in the orva-cel clinical trial, and note that all enrolled patients will be able to receive treatment per trial protocols, and patients who have received treatment will continue to be followed per protocol and regulatory requirements. The learnings we’ve generated from this research, as well as innovations in the manufacturing process, have made a significant impact on our current and future efforts in cell therapy. "

BMS added that it remained committed to the ongoing study of therapies for people living with aggressive blood cancers – such as Breyanzi, "our first FDA-approved CAR T cell therapy", and ide-cel, "our anti-BCMA CAR T-cell therapy in late-stage development in collaboration with bluebird bio – with the goal of bringing potentially life-changing therapies to more patients as quickly as possible".

The company also said that, with a robust clinical development portfolio, it constantly evaluated its programs "to prioritize resources where we see the greatest potential for transformational effects on patients’ lives."

*This article was updated on 15 February after it was initially published to include the information on orvacabtagene autoleucel (orva-cel).