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10 Cell and Gene Therapies to Watch in 2023

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With confidence building, numerous cell and gene therapies will likely go before the FDA and other global regulatory agencies this year, in addition to key data readouts.

2022 was nothing short of a roller coaster ride for the biotech space, particularly for those developing novel cell and gene therapies. Waves of layoffs and restructurings were met with a record-setting number of new gene therapy approvals, as well as a novel cell therapy approval for multiple myeloma and several new indications approved for existing cell therapies.

As more therapies are approved, the conversation is rightfully shifting from preclinical pipelines to that of actual treatments and the patients who will receive them, with 2023 shaping up to be an impressive year.

In line with bringing even more life-changing treatments to fruition, CGTLive chose to focus this year’s roundup on therapies that are within reach of the clinic. With several Prescription Drug User Fee Act (PDUFA) dates already on the calendar and a host of biologics license applications (BLAs) on the horizon, let’s look at 10 therapies we’ll have our eyes on in 2023.

1. Beremagene geperpavec (B-VEC); Krystal Biotech

A topical, redosable gene therapy, B-VEC is currently under FDA review for the treatment of dystrophic epidermolysis bullosa, a rare skin blistering disorder with currently no targeted approved treatment. The result of mutations in the COL7A1 gene that produce a protein that binds the different layers of skin together, B-VEC restores type VII collagen production by delivering functional copies of COL7A1 directly through patients’ open wounds. Current treatment is limited to supportive wound care and infection prevention. 

In a phase 3 trial, treatment with B-VEC was associated with 50% more wounds being completely healed at 3 months than with placebo, with patients having meaningful improvements in pain severity, as well.

Why it’s important: Dermatology approvals are having their day in front of the FDA, with 5 novel product approvals in 2022. The approval of B-VEC, which was recently pushed back to a PDUFA date of May 19, 2023 due to an amendment to the application, could help open the floodgates for other investigational gene therapies in conditions like ichthyosis, melanoma, and wound healing.

2. Afamitresgene autoleucel (afami-cel); Adaptimmune Therapeutics

Adaptimmune’s T-cell receptor (TCR) T-cell therapy, afami-cel, is the subject of a rolling BLA submission that, if accepted, may put one of the first engineered TCR cell therapies for a solid tumor in front of the FDA for approval. Indicated for the treatment of synovial sarcoma, the cell therapy targets the MAGE-A4 antigen using Adaptimmune’s SPEAR affinity-enhanced TCR T-cells.

Additional data from the phase 2 SPEARHEAD-1 trial in 52 participants were reported in Q4 2022, with 19 partial respondents, 27 cases of stable disease (51.9%), and 6 cases of progressive disease (11.5%), for a total objective response rate of 36.5% (95% CI, 23.62-51.04). Median duration of response was 50.3 weeks (range, 11.7-122.0+) in patients with synovial sarcoma, and the therapy had an acceptable safety profile overall.

Why it’s important: TCR-based cell therapies are a growing subset of T-cell immunotherapy that are garnering the attention of industry and investors alike. Adaptimmune is on track to potentially contribute to a cell therapy breakthrough in solid tumors that the industry has long-awaited.

3. AMT-130; UniQure 

UniQure is betting on its gene therapy, AMT-130, to be the breakthrough the world has been waiting for in Huntington disease (HD). The company has resumed enrollment and expects to report longer follow-up data from patients dosed in the phase 1/2 trial (NCT04120493) later in 2023 after a voluntary pause in August 2022 due to suspected unexpected severe adverse reactions of localized inflammatory responses and other related symptoms in 3 participants treated with the highest dose of AMT-130.

Why it’s important: AMT-130 is currently the furthest gene therapy in the pipeline for HD, and with waning competition, a lot of hope is resting on its shoulders. Previously, Voyager Therapeutics decided to stop developing VY-HTT01 after facing a clinical hold in 2021 in favor of a second-generation AAV approach, and BrainVectis’ BV-101 is currently recruiting for its phase 1/2 trial (NCT05541627) and has not yet reported any data.

4. NTLA-2001 and NTLA-2002; Intellia

Intellia is cornering the rare disease gene therapy market with 2 of its lead CRIPSR/Cas 9 gene editing candidates, NTLA-2001 and NTLA-2002. Early clinical data released in 2022 point to a promising future for the therapies, which are currently being evaluated for the treatment transthyretin (ATTR) amyloidosis with cardiomyopathy and hereditary angioedema, respectively. Demonstrating deep, durable treatment effect, Intellia announced plans to move forward with investigational new drug applications to expand study sites into the US for pivotal studies for both candidates. They also plan to launch a phase 3 study to evaluate NTLA-2001 in ATTR amyloidosis with polyneuropathy, making it the only gene therapy candidate currently in clinical trials for this indication.

Why it’s important: Intellia’s demonstrated success using in vivo gene editing provides real-world proof of concept for the gene therapy approach. Company executives are confident, calling the therapies a “functional cure” for their indications, and competitors, including BioMarin’s BMN331, are still a few large steps behind in the trial process.

5. Delandistrogene moxeparvovec (SRP-9001); Sarepta Therapeutics/Roche

Sarepta is looking forward to hitting a major milestone in May 2023: the PDUFA date for SRP-9001, the company’s gene therapy for Duchenne muscular dystrophy (DMD), which if approved, would mark the first gene therapy in the indication. Sarepta submitted a BLA under the accelerated approval pathway in September 2022 based off safety and efficacy data in 80 treated participants so far, with up to 4 years of follow-up post-treatment. Its randomized, placebo-controlled, phase 3 EMBARK study is ongoing, which Sarepta has branded as a post-marketing confirmatory trial.

Why it’s important: Sarepta nearly has the DMD treatment space cornered, with 3 approved antisense oligonucleotides on the market. The approval of SRP-9001 would mark a new chapter for the company and the disease, as the existing therapies leave something to be desired. Any slip-up in the process opens a door for several competitors, including Capricor and REGENXBIO, both of whom have clinical programs in progress.

6. Exagamglogene autotemcel (exa-cel); CRISPR/Vertex

Hot off the heels of the first of its kind approval of beti-cel (Zynteglo; bluebird bio) in transfusion-dependent beta thalassemia (TDT) is CRISPR/Vertex’s exagamglogene autotemcel (exa-cel), a double-hitter gene-edited therapy being evaluated in phase 2/3 trials for both TDT (CLIMB-THAL-111; NCT03655678) and sickle cell disease (SCD; CLIMB-SCD-121; NCT03745287).

Exa-cel has demonstrated an ability to reduce the need for transfusions in TDT and vaso-occlusive events in SCD. Recent data show that 42 patients (95%) reached transfusion independence (follow-up, 0.8-36.2 months), with the remaining 2 patients achieving a 75% and 89% reduction in transfusion volume. All patients (100%) with SCD were free of VOCs (follow-up, 2.0-32.3 months).

Why it’s important: With a rolling BLA for both therapies set to be complete by the end of Q1 2023, there’s a good chance that exa-cel could be the very first ex vivo gene-edited therapy approved.

7. Tablecleucel (tab-cel); Atara Biotherapeutics

Tablecleucel (tab-cel) made the news in December 2022 after it became the first allogeneic T-cell therapy to be approved after the European Commission gave it the green light. The therapy, marketed as Ebvallo, was approved as a monotherapy for the treatment of adult and pediatric patients 2 years of age and older with relapsed or refractory Epstein‑Barr virus positive (EBV+) post‑transplant lymphoproliferative disease (PTLD) who have received at least 1 prior therapy. Atara Biotherapeutics is now pursuing an approval in the US and is planning to meet with the FDA in the first quarter of 2023 to gain clarity on a BLA pathway for tab-cel.

Tab-cel yielded a 51.2% overall response rate in 43 patients with EBV+PTLD after solid organ transplant (SOT) or hematopoietic cell transplant (HCT) in data presented in December’s Annual Society of Hematology meeting from the phase 3 ALELLE study (NCT03394365). The median time to response was 1 month, median duration of response in 22 responders was 23 months, and overall survival was 18.4 months.

Why it’s important: EBV (and Atara) have been a hot topic this year, with the company gaining attention for its EBV-targeted therapy for multiple sclerosis after major epidemiological data made the headlines. Its success with tab-cel lends further credibility to its focus on EBV, making it an especially interesting candidate.

8. Lifileucel; Iovance Therapeutics

Despite a recent setback in its rolling BLA submission, Iovance is on track to submit its investigational tumor infiltrating lymphocyte (TIL) therapy lifileucel by the end of Q1 2023. Its acceptance could mark a significant breakthrough in solid tumors, notably melanoma and cervical cancer.

Data presented at SITC 2022 from its phase 2 trial showed an objective response rate of 31.4% in the 2 cohorts from which data were presented, with 9 complete responses and 39 partial responses. Median duration of response (DOR) was not reached at a median follow up of 36.5 months, and 41.7% of responding patients had a DOR of 24 months or more. Median overall survival (OS) was 13.9 months, and the 12-month OS rate was 54% (95% CI: 45.6%-61.6%).

Why it’s important: Success in this category for Iovancewould bolster its advancing pipeline of mono- and combination TIL therapies, as well as the pipelines of competitors like Tilt Biotherapeutics, whose phase 1 trial in melanoma and head and neck squamous cell carcinoma is currently recruiting.

9. MCO-010; Nanoscope

The world of ophthalmic gene therapies is awaiting a major readout in the first half of 2023 from Nanoscope’s MCO-010, an optogenetic gene therapy intended to treat retinitis pigmentosa and Stargardt disease. The Phase 2 study’s primary efficacy end point is the Y-mobility test, which measures patients’ ability to navigate between LEDs lights in a dimly lit room.

Why it’s important: With only 1 other approved therapy for an inherited retinal disease, Nanoscope’s success could open a new chapter in this therapeutic space that’s ripe for expansion.

10. Fidanacogene elaparvovec (PF-06838435); Pfizer

Topline results announced at the end of 2022 showed that treatment with a single infusion of fidanacogene elaparvovec, Pfizer’s investigational gene therapy for the treatment of severe hemophilia B, demonstrated non-inferiority and even superiority in annualized bleeding ratescompared with factor IX treatment, according to findings from the phase 3 BENEGENE-2 study (NCT03861273). Pfizer expects to readout additional data in the first half of 2023 and will continue discussions with regulatory agencies.

Why it’s important: Pfizer’s data comes hot on the heels of CSL Behring and UniQure’s EtranaDez (Hemgenix) approval, which is currently the only therapy approved for the hemophilia B indication. Further success in this space could mean a significant change in the treatment landscape and outcomes for patients.