Eight Global CGT Therapies Approved in H1 2024: Innovators File for IPOs

Jul 08, 2024 11:57 CST Updated 11:57

Geron

Cancer Treatment Product Developer

Sarepta

Developer of Therapies for Rare Neuromuscular Diseases

Moderna

mRNA Therapeutics Developer

Pfizer

Pharmaceutical R&D Developer

Orchard Therapeutics

Gene Therapy Developer

Disclaimer: Due to limited proficiency, errors are inevitable, and some information may not be the most up-to-date. Comments pointing out any issues are welcome. This article is only an introduction to pharmaceuticals related to healthcare and is not a recommendation of treatment plans (if involved); this article does not constitute any investment advice.

Cell and Gene Therapy (CGT) is an emerging treatment modality in recent years. Unlike other therapeutic modalities, CGT has the potential to achieve "one-time treatment, permanent cure," offering hope for many patients to be free from long-term suffering. According toStatistics show that a total of 8 CGT therapies were approved for marketing worldwide in the first half of 2024. The editor summarizes as follows:

Sarepta: Elevidy Receives Full FDA Approval

On June 20, Sarepta Therapeutics, a leader in small nucleic acid drugs, announced that the U.S. FDA had approved the expanded indication for its Duchenne muscular dystrophy (DMD) gene therapy, Elevidys, to include patients at least 4 years of age. The FDA granted traditional approval for ambulatory patients and accelerated approval for non-ambulatory patients.

Under the accelerated approval pathway, Sarepta has committed to conducting and submitting the results of a randomized controlled trial to verify and confirm the clinical benefit of Elevidys in non-ambulatory DMD patients. The ENVISION (SRP-9001-303) trial is currently underway, a global, randomized, double-blind, placebo-controlled Phase 3 study targeting non-ambulatory and older ambulatory DMD patients, serving as the confirmatory trial for this post-marketing requirement.

As early as June 2023, the U.S. FDA granted accelerated approval to the DMD gene therapy Elevidys for the treatment of pediatric patients aged 4 to 5 with Duchenne muscular dystrophy, priced at $3.2 million per dose. This is the world's first approved AAV gene therapy for Duchenne muscular dystrophy.Now, Elevidys has been approved for use in DMD patients ≥4 years old, regardless of their ability to walk, which is of great significance for the treatment of DMD patients.

Geron：Rytelo

On June 6, Geron Corp announced that the U.S. FDA had approved its "first-in-class"OligonucleotideTelomerase Inhibitor Rytelo (imetelstat) for TreatmentTransfusion-Dependent Anemia in Patients with Lower-Risk Myelodysplastic Syndromes (LR-MDS)。Rytelo is the first telomerase inhibitor approved by the U.S. FDA.Since telomerase was discovered in 1984,After nearly 40 years of waiting, the industry has finally welcomed the first telomerase-targeted therapy. Rytelo was listed by the industry media Evaluate as one of the top 10 this year.Potential BlockbusterOne of the therapies.

FDA Approval of RYTELTO Was Based on the IMerge Phase 3 Clinical Trial Results Published in The Lancet. IMergeThe trial met its primary endpoint and key secondary endpoints.Compared with placebo, the rate of RYTELO achieving at least 8 consecutive weeks without red blood cell (RBC-TI) infusion was significantly higher (RYTELO 39.8% [95% CI 30.9-49.3]; placebo 15.0% [7.1-26.6]; p<0.001), and at least 24 consecutive weeks.Higher RBC-TI Ratio(RYTELO 28.0% [95% CI 20.1-37.0]; placebo 3.3% [95% CI 0.4-11.5]; p<0.001). Among those treated with RYTELO, RBC-TI demonstrated durability and sustainability, with median RBC-TI durations of approximately 1 year for 8-week responders and 1.5 years for 24-week responders.

Following the approval of Rytelo, Geron Corp's stock price surged by 22%. Evaluate forecasts that by 2028, Rytelo’s sales are expected to reach $737 million. This projection reflects market recognition of Rytelo's therapeutic potential.Geron Corp has set a clear pricing strategy for Rytelo, with the wholesale purchase cost of a single 47-milligram dose at $2,471, while the purchase cost of a single 188-milligram dose is $9,884. The dosage will be determined and adjusted based on the patient’s weight.

Moderna：mRESVIA

On May 31, Moderna, Inc. (NASDAQ: MRNA) announced that the U.S. Food and Drug Administration (FDA) had approved an mRNA Respiratory Syncytial Virus (RSV) vaccine, mRESVIA.(mRNA -1345), for protecting adults aged 60 and above from lower respiratory tract diseases caused by RSV infection. It isCurrently, the only RSV vaccine administered via a pre-filled syringe, marking the first time an mRNA vaccine has been approved for use in diseases other than COVID-19.

This approval is based on the positive data from the Phase 3 clinical trial ConquerRSV, a global study conducted among approximately 37,000 adults aged 60 years or older across 22 countries. The primary analysis with a median follow-up of 3.7 months found the vaccine to be 83.7% (95.88% CI 66.0%, 92.2%) effective in preventing RSV lower respiratory tract disease (LRTD). These results were published in The New England Journal of Medicine. Another long-term analysis indicated continued protection against RSV LRTD during a median follow-up period of 8.6 months.According to the report, no serious safety issues were found in the Phase 3 trial. The most common adverse reactions were injection site pain, fatigue, headache, myalgia, and arthralgia.

Pfizer:BEQVEZ

On April 26, 2024, Pfizer announced that the U.S. FDA had approved its gene therapy BEQVEZ (fidanacogene elaparvovec-DZKT), based on an adeno-associated virus (AAV) vector, for marketing. It is used to treat moderate to severe hemophilia B in adult patients (18 years and older) who test negative for neutralizing antibodies to AAV serotype Rh74. It is reported that,BEQVEZ is priced at $3.5 million, consistent with the price of Hemgenix, a gene therapy for hemophilia B previously developed and approved by UniQure.

This approval is mainly based on the positive data from the Phase III BENEGENE-2 study (n=45).The results showed that within 12 months of receiving a single dose of BEQVEZ, the annualized bleeding rate (ABR) in patients was significantly reduced compared to the standard prophylactic treatment group (receiving FIX drugs as preventive replacement therapy) (1.3 vs. 4.43, P<0.0001), meeting both non-inferiority and superiority criteria.

BEQVEZ is currently under review by the European Medicines Agency (EMA) and has recently received approval from Canadian regulatory authorities. Apart from BEQVEZ,Pfizer currently has two Phase III projects studying gene therapy., Both projects target populations with high unmet needs:Hemophilia A and Duchenne muscular dystrophy. In addition, a phase 3 trial is investigating marstacimab, a novel anti-tissue factor pathway inhibitor, for the treatment of hemophilia A or hemophilia B without factor VIII (FVIII) or factor IX (FIX) inhibitors. Currently, the FDA and EMA are reviewing the Biologics License Application and the European Marketing Authorization Application for marstacimab, respectively.

Orchard：Lenmeldy

On March 18, the FDA approved Lenmeldy, a gene therapy developed by Orchard Therapeutics, for the treatment of children with metachromatic leukodystrophy (MLD). Priced at $4.25 million, it surpasses Hemgenix to become the most expensive drug in history.Lenmeldy is the only FDA-approved therapy for treating children with early-onset metachromatic leukodystrophy (MLD)., This gene therapy was approved in the EU in 2020 and in the UK in 2022, with a market price of £2.8 million (approximately $3.51 million, at the latest exchange rate of £1 ≈ $1.2526).USD calculation).

Lenmeldy (atidarsagene autotemcel, formerly known as OTL-200) isOrchard's Core Technology: Autologous Stem Cell Ex Vivo Modification and Reinfusion Gene TherapyDeveloped, which aims to use lentiviral vectors to introduce the ARSA transgene encoding arylsulfatase-A into autologous CD34-positive hematopoietic stem and progenitor cells of MLD patients, thereby restoring arylsulfatase-A expression through a one-time treatment to halt or slow disease progression.

This FDA approval is based on data from 37 children.After 12 years of follow-up (median time 6.76 years), compared with untreated children, patients treated with Lenmeldy showed a significantly prolonged overall survival and a significant reduction in motor disorders or death. In terms of safety, Lenmeldy demonstrated good tolerability, with no treatment-related serious adverse events or deaths.

BMS:Breyanzi

On March 14, Bristol Myers Squibb announced that the U.S. FDA has granted accelerated approval to Breyanzi (lisocabtagene maraleucel; liso-cel). This is a CD19-directed CAR-T cell therapy for the treatment of adult patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL) or small lymphocytic lymphoma (SLL) who have previously received at least two lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor. The press release noted,This cellular therapy is the first CAR-T cell therapy for adult patients with relapsed or refractory CLL or SLL.

Breyanzi is an autologous CAR-T cell therapy targeting the CD19 antigen, with a defined composition and 4-1BB co-stimulatory domain.It was approved by the FDA in February 2021 for the treatment of adult patients with relapsed/refractory large B-cell lymphoma (LBCL) who have received two or more systemic therapies.The uniqueness of this therapy lies in the controlled ratio of CD8-positive and CD4-positive T cells in the CAR-T therapy, which can better manage the toxic side effects of cellular therapy.The 4-1BB signaling domain enhances the expansion and persistence of CAR-T cells.

According to the press release, this indication was granted accelerated approval based on the response rate and duration of response. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trials.This approval is based on the TRANSCEND CLL 004 trial, an open-label, single-arm, multi-center clinical Phase 1/2 trial.Data analysis shows that the trial has reached its primary endpoint,20% of patients with relapsed or refractory CLL or SLL treated with Breyanzi achieved complete response (CR), and the safety profile has been confirmed.

CARsgen Therapeutics: Zevor-cel Injection

On March 1, CARsgen Therapeutics announced that the National Medical Products Administration ("NMPA") has approved the New Drug Application ("NDA") for its BCMA CAR-T product, Cilta-cel® (Zevor-cel Injection), for the treatment of adult patients with relapsed or refractory multiple myeloma who have progressed after receiving at least three prior lines of therapy (including at least one proteasome inhibitor and one immunomodulatory agent).Zevor-cel is the fifth CAR-T therapy approved in China.

On March 5, CARsgen Therapeutics disclosed the initial price of its CAR-T cell therapy Zevor-cel Injection (brand name: Sikaz) as11.5 million yuan,After jointly estimating with its partner, Huadong Medicine (000963.SZ), the peak annual end-market sales of the drug are expected to reach over 1 billion yuan.

SaiKaiZe® is an autologous BCMA-targeted CAR-T cell product generated through lentiviral transduction of T cells. The lentivirus-encoded CAR includes a fully human BCMA-specific single-chain variable fragment (“scFv”), human CD8α hinge domain, CD8α transmembrane domain, 4-1BB co-stimulatory domain, and CD3ζ activation domain. The independently developed new fully human scFv exhibits high binding affinity and stability.CARsgen Pharma is advancing a Phase 1b/2 clinical trial (LUMMICAR STUDY 2) in North America to evaluate the safety and efficacy of ThermoCure® for the treatment of relapsed or refractory multiple myeloma.

January 2023,CARsgen Therapeutics and Huadong Medicine Reach Commercialization Collaboration for Thelz® in Mainland ChinaCARsgen Pharma granted Huadong Medicine the exclusive commercial rights to SAIKEZE® in mainland China. According to the agreement, Huadong Medicine (Hangzhou) will pay 200 million RMB as an upfront payment to Kaixin Life, a wholly-owned subsidiary of CARsgen Pharma, along with up to 1.025 billion RMB in registration and sales milestone payments.

Iovance：Amtagvi

On February 16, Iovance Biotherapeutics announced that the FDAAccelerated approval was granted for the company's Tumor Infiltrating Lymphocyte (TIL) therapy Amtagvi (lifileucel) to treat advanced melanoma.Priced at $515,000。It is reported that lifileucel is the world's first approved and marketed TIL cell therapy.

Amtagvi is a tumor-derived autologous T-cell immunotherapy. In a pre-treatment surgical procedure, a portion of the patient's tumor tissue is excised, the patient’s T cells are isolated from the tumor tissue, further processed, and then returned to the same patient in the form of a single-dose infusion. A single dose of Amtagvi contains 750 million to 7.2 billion viable cells, and it takes approximately 34 days from receiving the tumor tissue to completing the preparation of Amtagvi.

Amtagvi Phase 2 Clinical Trial Shows: At a Median Follow-Up of 27.6 Months, the Objective Response Rate (ORR) Was 31.4%, Including 8 Patients Achieving Complete Response (CR) and 40 Patients Achieving Partial Response (PR). Later, Iovance’s 4-Year Follow-Up Data Revealed the Longest Duration of Response to Be 55.8 Months.

Clinical Trial Safety Data:

Summary

Five CGT Therapies Expected to Be Approved for Market Launch in 2024, including:Hengrui Dasheng's CAR-T CellsTreatment Product: Rundadecartiximab Injection、Adaptimmune TherapeuticsTCR T-Cell TherapyEkyolumab,BioCardia'sCardiAMP、Pfizer'sNovel Investigational Gene TherapyFidanacogene elaparvovec、Autolus Therapeutics' CAR-T Cell TherapyObecabtagene autoleucelRocket Pharmaceuticals' gene therapy Kresladi andAbeonSarepta Therapeutics' investigational autologous cell therapy Prademagene zamikeracel (pz-cel) respectivelyJune and AprilRejected by FDA Due to CMC Issues，FDA Requests Additional CMC Information to Complete Review.

Reference: Announcements from various companies