372 Gene Therapy Clinical Trials Underway Globally, with 25 Emerging Therapies Poised for Market

The Q1 2019 Quarterly Global Regenerative Medicine Data Report, released by the Alliance for Regenerative Medicine (ARM), indicates a growth in the number of clinical trials involving gene therapy. By the end of the first quarter, there were 372 gene therapy clinical trials underway globally. Among these, the majority were in Phase II, with 217 trials accounting for 58%; this was followed by 123 trials in Phase I, representing 33%; and 32 trials in Phase III, comprising 9%.

Compared with the data at the end of 2018, the number of gene therapy clinical trials increased by 10; compared with the 319 trials in the same period of 2018, this represents a year-on-year increase of 17%.

The pace of acquisitions in the gene therapy sector is also heating up. On April 15, Catalent announced that it had agreed to acquire Paragon Bioservices for $1.2 billion, aiming to expand its gene therapy capabilities. Thermo Fisher Scientific plans to complete its $1.7 billion acquisition of Brammer Bio, a viral vector CDMO, by the end of the second quarter, which will further strengthen its presence in this field.

In February this year, when Roche announced its plan to acquire Spark Therapeutics for $4.8 billion, the largest gene therapy M&A deal of the year had arrived. However, resistance from Spark’s shareholders and regulatory scrutiny forced Roche to extend its tender offer deadline three times, making the transaction fraught with difficulties.

Two candidate drugs considered close to approval appear on this list. One is Zynteglo (formerly known as LentiGlobin), a gene therapy for thalassemia and sickle cell disease developed by Bluebird Bio. It has received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA), recommending conditional approval for Zynteglo. This is typically a reliable indicator of final approval by the European Commission (EC). The EC usually follows the CHMP’s recommendation and is expected to make its final review decision within approximately two months.

Another is Novartis’s AveXis’s Zolgensma (formerly known as AVXS-101). Zolgensma is a gene therapy for spinal muscular atrophy, and its anticipated multimillion-dollar price tag has garnered more media attention than its positive Phase III trial data.

Genengnews compiled a list of 25 “emerging” gene therapies, including Zynteglo and Zolgensma, by aggregating data from ARM, ClinicalTrials.gov, and company announcements. Each therapy is detailed by name, sponsor company, indication, mechanism of action, trial registration number, and latest development updates.

Axalimogene filolisbac (AXAL, ADXS11-001) and ADXS-DUAL

Company: Advaxis

Indication: Metastatic Cervical Cancer

Mechanism: A platform technology-based targeted immunotherapy, this drug utilizes live, attenuated Listeria monocytogenes (Lm) engineered to produce and deliver tumor antigen/adjuvant fusion proteins within antigen-presenting cells, thereby eliciting a robust T cell-mediated immune response. ADXS-DUAL is the second-generation version of axalimogene filolisbac.

Clinical Trials (Registration Numbers): Study of ADXS11-001 in Patients with High-Risk Locally Advanced Cervical Cancer (AIM2CERV, NCT02853604, Phase III); Preoperative Vaccination with ADXS-11-001 Prior to Robotic Surgery for HPV-Positive Oropharyngeal Cancer (NCT02002182, Phase II)

Latest Development: On May 15, the FDA partially placed a clinical hold on the AIM2CERV trial. This partial hold appears to be related to Advaxis’s proposed amendments to the trial’s statistical analysis plan and various chemistry, manufacturing, and controls (CMC) issues. Advaxis’s axalimogene filolisbac is also being evaluated in combination therapy trials with Merck’s Keytruda (pembrolizumab), Bristol Myers Squibb’s Opdivo (nivolumab), and AstraZeneca’s Imfinzi (durvalumab).

AMT-061

Company: uniQure

Indication: Hemophilia B

Mechanism: AMT-061 consists of an AAV5 vector carrying the gene encoding the Padua variant of factor IX (FIX-Padua).

Trials (Registration Numbers): NCT03569891 (HOPE-B, Phase III); NCT03489291 (Phase IIb)

Latest Update: On May 10, uniQure presented updated clinical data. The results showed that factor IX (FIX) activity increased significantly in all three patients six months after a single dose of AMT-061. FIX activity reached 51% of normal levels in the first patient, 33% in the second patient, and 57% in the third patient.

Fidanacogene elaparvovec (formerly SPK-9001 and PF-06838435)

Company: Pfizer

Indications: Hemophilia B

Mechanism: Bioengineered adeno-associated virus (AAV) capsid (protein shell) and high-activity human coagulation factor IX gene.

Clinical Trial (Registration Number): NCT03587116 (Phase III)

Latest Development: Spark Therapeutics’ SPK-9001 has become Pfizer’s fidanacogene elaparvovec. In July 2018, the two companies initiated a Phase III program to evaluate the efficacy and safety of the investigational gene therapy fidanacogene elaparvovec as a prophylactic factor IX replacement therapy for hemophilia B.

Generx（alferminogene tadenovec，Ad5FGF-4）

Companies: Angionetics, Huapont Life Sciences (exclusive distribution and licensing agreement in China)

Indications: Refractory angina (Phase III), Cardiac Syndrome X (Phase I/II), Ischemic heart failure (Phase I/II), Moyamoya disease (IND-enabling), Cerebral ischemia (candidate selection)

Mechanism of Action: Generx consists of the human fibroblast growth factor-4 (FGF-4) gene, CMV promoter sequence, and signal peptide, encapsulated within a human serotype 5 adenovirus. Generx is delivered to the heart using Angionetic’s optimized cardiac catheterization technology, where it binds to cardiac cells via the coxsackie-adenovirus receptor and transfects the cells with the FGF-4 gene.

Clinical trial (registration number): NCT02928094 (AFFIRM, Phase III)

Latest Update: NCT02928094 is expected to start on June 1, 2019, with a primary completion date of June 1, 2021. Angionetics is a subsidiary of Gene Biotherapeutics (formerly Taxus Cardium Pharmaceuticals Group) but operates independently. Last year, Angionetics announced plans to secure external financing for the clinical development and commercialization of Generx, which may include an initial public offering (IPO) in 2019.

GS010

Company: GenSight Biologics

Indications: Leber hereditary optic neuropathy (LHON) caused by ND4 gene mutations

Mechanism: AAV2 gene therapy vector encoding human wild-type ND4 protein

Clinical trials (registration numbers): NCT02652780 (REVERSE, Phase III), NCT02652767 (RESCUE, Phase III), NCT03293524 (REFLECT, Phase III).

Latest Update: On May 15, GenSight reported positive 96-week results from the REVERSE trial, demonstrating that GS010 maintained efficacy two years after injection. At week 96, eyes treated with GS010 showed a mean improvement of -0.308 LogMAR compared to baseline. The company had previously announced positive 72-week results on May 6.

Instiladrin（n adofaragene firadenovec/Sny3; rAd-IFN/Syn3）

Companies: FKD Therapies, Ferring Pharmaceuticals

Indications: Non-muscle-invasive bladder cancer unresponsive to Bacillus Calmette-Guérin (BCG)

Mechanism: Instiladrin is a non-replicating adenovirus serotype 5 (Ad5) vector. It carries the gene encoding interferon alpha-2b (IFNα2b) and is administered in combination with the adjuvant Syn3 (rAD-IFN/Syn3).It can infect nearby tumor cells and activate the expression of the IFNα-2b gene within the cells.

Clinical Trial (Registration Number): NCT02773849 (Phase III)

Latest Developments: In 2018, Ferring Pharmaceuticals acquired global commercialization rights to nadofaragene firadenovec/Syn3 from FKD Therapies. On May 5, 2019, Dr. Colin Dinney of the MD Anderson Cancer Center presented updated three-year Phase II data in patients with bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer treated with Instiladrin. Among 34 male patients included in the follow-up study, 24 remained alive three years after treatment. Of the remaining 10 patients, three died from bladder cancer and seven from other causes.

Lenti-D

Company: Blue Bird Bio

Indications: Cerebral Adrenoleukodystrophy (CALD)

Mechanism: Transplantation of the patient’s own stem cells, with modification of the ABCD1 gene, which encodes the functional adrenoleukodystrophy protein (ALDP).

Clinical trials (registration numbers): NCT03852498 (ALD-104, Phase III); NCT01896102 (Starbeam or ALD-102, Phase II/III); NCT02698579 (long-term follow-up)

Latest Update: On May 2, 2019, Bluebird Bio announced that the first patient was treated in the ALD-104 clinical trial in April. The primary endpoint of the trial is sustained survival over 24 months without any loss in six major functional domains.

LYS-SAF302

Companies: Lysogene, Regenxbio, Sarepta Therapeutics

Indications: Mucopolysaccharidosis type IIIA (MPS IIIA), also known as Sanfilippo syndrome type A

Mechanism: Injection of AAVrh10 virus containing the healthy N-sulfoglucosamine sulfohydrolase (SGSH) gene into the brain can stimulate the production of enzymes that break down heparan sulfate, thereby slowing or halting disease progression.

Clinical trial: NCT03612869 (AAVance, Phase II/III);

NCT02746341 (SAMOS, Natural History Study)

Latest Update: On April 29, 2019, Lysogene announced that it expected to complete patient enrollment for the AAVance trial in the first half of 2020. The first patient was enrolled in December 2018 and received treatment two months later. In October 2018, Sarepta Therapeutics acquired the commercialization rights to LYS-SAF302 in the United States and other European regions, a deal that could generate over $125 million in revenue for Lysogene. Notably, LYS-SAF302 utilizes Regenxbio’s NAV AAVrh10 vector.

Nexagon

Companies: Eyevance Pharmaceuticals, OcuNexus Therapeutics

Indications: Persistent epithelial defects (PED) of the cornea refractory to current standard therapy

Mechanism: Downregulates the expression of the gap junction protein Cx43 via natural, unmodified oligonucleotides (30-mer). Nexagon can be formulated on contact lenses or amniotic membranes to ensure contact with the cornea or conjunctiva, allowing sufficient time for the active pharmaceutical ingredient to enter cells.

Clinical trials (registration number): Not available. Nexagon was the subject of eight early-stage studies, five of which have been completed, two terminated, and one withdrawn.

Latest Developments: In October 2018, Eyevance acquired the global rights to Nexagon from OcuNexus for an undisclosed sum. Reportedly, Eyevance is funding a pivotal trial expected to commence in 2019. At the Ophthalmology Innovation Summit on November 5, 2018, Dr. Mark Jasek, Chief Scientific Officer of Eyevance, stated that they would evaluate the potential therapeutic efficacy of Nexagon for PED caused by burns or chemical injuries in a Phase IIb study.

NSR-REP1

Company: Nightstar Therapeutics

Indication: Choroideremia

Mechanism: The AAV2 vector is loaded with recombinant human complementary DNA (cDNA) to produce REP1 within the eye. During surgery, NSR-REP1 will be administered via subiris injection.

Clinical trials (registration numbers): NCT03496012 (STAR, Phase III); NCT03507686 (GEMINI, Phase II); NCT03584165 (SOLSTICE, long-term follow-up)

Latest Development: On March 4, 2019, Nightstar announced its acquisition by Biogen for approximately $877 million. Biogen aims to supplement its ophthalmology drug pipeline with NSR-REP1. On May 8, Nightstar shareholders approved the acquisition, with the transaction expected to close on June 7. Data from NCT03496012 are expected to be disclosed in the second half of 2020.

OTL-101

Companies: Orchard Therapeutics, Great Ormond Street Hospital for Children NHS Foundation Trust

Indications: Adenosine Deaminase Severe Combined Immunodeficiency (ADA-SCID)

Mechanism: Autologous and ex vivo hematopoietic stem cell gene therapy.

Clinical Trial (Registration Number): NCT03765632 (Phase I/II)

Latest Update: On February 22, 2019, Orchard announced positive two-year follow-up results from the registration trial of the new OTL-101 formulation, which enrolled a total of 20 patients. Over the 24-month period, overall survival was 100% and event-free survival was 100% among patients treated with OTL-101 at both the 88% and 56% dose levels. Dr. Andrea Spezzi, Chief Medical Officer of Orchard, stated that the company plans to submit a Biologics License Application (BLA) in 2020.

OTL-103 (formerly GSK2696275)

Companies: Orchard Therapeutics, Ospedale San Raffaele-Telethon Institute for Gene Therapy (OSR-TIGET)

Indications: Wiskott-Aldrich Syndrome (WAS)

Mechanism: Genetically modified autologous hematopoietic stem cells. Hematopoietic stem cells are collected from bone marrow or peripheral blood and transduced with a lentiviral vector encoding the WAS gene.

Clinical Trials (Registration Numbers): NCT01515462 (TIGET-WAS, Phase II); NCT03837483 (Phase II)

Latest Update: Orchard acquired OTL-103 from GlaxoSmithKline last year. On March 21, Orchard announced the three-year follow-up data for eight patients enrolled in trial NCT01515462 and confirmed that its plans to initiate enrollment for trial NCT03837483 remain unchanged.

OTL-200 (formerly GSK2696274)

Companies: Orchard Therapeutics, Ospedale San Raffaele-Telethon Institute for Gene Therapy (OSR-TIGET)

Indication: Metachromatic Leukodystrophy (MLD)

Mechanism: Autologous CD34+ cells transduced with a lentiviral vector carrying human arylsulfatase A (ARSA) cDNA

Clinical Trial (Registration Number): NCT03392987 (Phase III)

Latest Developments: In 2018, Orchard acquired OTL-200 from GlaxoSmithKline. On March 26, 2019, Orchard submitted registration data from the Phase I/II trial (NCT01560182): motor function scores in late-infantile patients increased by 65% and 72% at 2 and 3 years post-treatment, respectively, while early-juvenile patients showed a 40% improvement. Orchard intends to submit regulatory filings in 2020 as previously planned.

OXB-301（TroVax、MVA-5T4）

Organizations: Oxford BioMedica, University College London, Cancer Research UK

Indications: Ovarian cancer, colorectal cancer

Mechanism: A cancer vaccine whose main component is the attenuated, modified vaccinia virus Ankara (MVA). OXB-301 is designed to deliver the 5T4 carcinoembryonic antigen gene, aiming to destroy cancer cells by stimulating the immune system.

Clinical trial (registration number): NCT01556841 (TRIOC, Phase II)

Latest Update: NCT01556841 was completed on May 9, 2018. In September 2018, Oncoimmunology published the results of the Phase II SKOPOS trial (NCT01569919). The results showed that 95.6% of patients developed cellular or humoral immune responses against 5T4, meeting the study’s primary endpoint (>64%). Disease control was observed in 87% of patients, including 69.6% with stable disease and 17.4% with partial response.

Pexa-Vec（Pexastimogene devacirepvec、JX-594）

Companies: SillaJen, Transgene, Beijing Shenyuan Pharmaceutical Group, Lee's Pharmaceutical, GC Pharma

Indications: Hepatocellular carcinoma

Mechanism: The Wyeth strain of vaccinia virus has been engineered to directly lyse tumor cells and stimulate anti-tumor immunity.

Clinical trials (registration numbers): NCT02562755 (PHOCUS, Phase III), NCT03071094 (Phase I/II)

Latest Update: On March 20, SillaJen announced the issuance of KRW 110 billion (approximately USD 97.3 million) in convertible bonds to fund clinical trials of Pexa-Vec. The clinical studies will evaluate the efficacy of Pexa-Vec in liver and breast cancers, head and neck cancer, and neuroendocrine tumors. Transgene stated that preliminary data from the PHOCUS trial (interim data from NCT03071094) are expected to be released later this year. Transgene holds the commercial rights to Pexa-Vec in Europe.

ProstAtak (aglatimagene besadenovec、AdV-tk)

Company: Advantagene (d/b/a Candel Therapeutics)

Indications: Prostate cancer, hepatocellular carcinoma, pancreatic cancer, non-small cell lung cancer

Mechanism: ProstAtak is based on Advantagene’s gene-mediated cytotoxic immunotherapy (GMCI) technology platform and consists of aglatimagene besadenovec and valacyclovir. Aglatimagene besadenovec (AdV-tk) is an engineered adenovirus-derived gene vector that delivers the thymidine kinase (tk) gene from herpes simplex virus to target cells. In clinical practice, AdV-tk is administered via injection directly into the patient’s tumor site, prompting the target tissue and cells to produce the TK protein.

Clinical Trials (Registration Numbers): NCT01436968 (PrTK03, Phase III); NCT02768363 (ULYSSES, Phase II/III); NCT03313596 (LT-03, Phase III); NCT03576612 (Phase I)

Latest Developments: On April 1, Advantagene (operating as Candel Pharmaceuticals) announced that it had secured $22.5 million in Series C financing, led by Northpond Ventures. Additionally, on March 21, Candel announced the completion of enrollment for the first cohort of patients with high-grade glioma in trial NCT03576612.

RT-100 (AC6 Gene Transfer)

Company: Renova Therapeutics

Indications: Heart failure with reduced ejection fraction (HFrEF)

Mechanism: RT-100 is administered via intracardiac catheterization, directly infusing into the arteries supplying the heart. It delivers a gene encoding human AC6 protein into the body using a modified adenoviral vector (Ad5.hAC6), which can enter cells but cannot replicate itself.

Clinical Trial (Registration Number): NCT03360448 (FLOURISH, Phase III)

Latest Update: As of December 18, 2018, according to the latest information posted on ClinicalTrials.gov, clinical trial NCT03360448 had not yet begun recruiting patients.

SPK-8011

Company: Spark Therapeutics (acquired by Roche)

Indications: Hemophilia A

Mechanism of Action: Utilizing bioengineered adeno-associated virus (AAV) vectors to activate the AAV-LK03 capsid.

Clinical Trials (Registration Numbers): NCT03003533 (Phase I/II), NCT03432520 (Long-term Follow-up Study), NCT03876301 (Prospective, Observational Study)

Latest Update: In 2018, Spark advanced SPK-8011 into Phase III clinical trials, initiating the program with a six-month observational run-in study. In December 2018, Spark announced preliminary interim data from its ongoing Phase I/II trial involving 12 participants. The results demonstrated a 94% reduction in bleeding episodes and a 95% reduction in FVIII infusion usage across all three dose cohorts, starting four weeks after vector infusion.

Toca 511 (vocimagene amiretrorepvec) and Toca FC

Companies: Tocagen, ApolloBio

Indications: Recurrent high-grade glioma (Phase II/III), metastatic solid tumors including colorectal cancer, renal cell carcinoma, melanoma, pancreatic cancer, lung cancer, and breast cancer (Phase I), newly diagnosed high-grade glioma (preclinical)

Mechanism of Action: This is a two-component cancer immunotherapy. Toca 511 is an injectable retroviral replicating vector (RRV) that encodes the prodrug-activating enzyme cytosine deaminase (CD). Toca FC is an extended-release oral formulation of the prodrug 5-fluorocytosine (5-FC), which is converted into 5-fluorouracil (5-FU) in the presence of CD.

Clinical Trials (Registration Numbers): NCT02414165 (Toca 5, Phase II/III), NCT02576665 (Toca 6, Phase I), NCT02598011 (Toca 7, Phase I)

Latest Update: In April 2019, Tocagen announced preclinical data for its therapy, demonstrating that the combination of Toca 511/Toca FC with temozolomide or cyclophosphamide improved survival rates. Tocagen stated that these results were sufficient to support the planned Phase II/III NRG-BN006 trial, which aims to evaluate Toca 511/Toca FC against the standard of care in patients with newly diagnosed glioblastoma. Enrollment for the NRG-BN006 trial was expected to begin in the second half of 2019.

Valoctocogene Roxaparvovec (formerly BMN 270)

Company: BioMarin Pharmaceutical

Indication: Hemophilia A

Mechanism of Action: AAV-Factor VIII Vector

Trials: NCT03370913 (BMN270-301 or GENEr8-1, Phase III); NCT03392974 (BMN270-302, also known as GENEr8-2; Phase III)

Latest Update: On April 25, BioMarin announced that it expects to complete enrollment for the clinical trial NCT03370913 in the third quarter of 2019. In addition, BioMarin has already submitted certain documentation required for potential accelerated approval, in accordance with the draft guidance on hemophilia gene therapy products issued by the FDA in 2018.

VB-111（ofranergene obadenovec）

Companies: VBL Therapeutics (Vascular Biogenics), NanoCarrier (commercialization rights in Japan)

Indications: Solid tumors, including recurrent platinum-resistant ovarian cancer (Phase III)

Mechanism: A biologic agent targeting oncogenes, administered via intravenous injection every two months. VB-111 is developed based on VBL’s Vascular Targeting System (VTS™). VBL states that VB-111 combines two anti-tumor mechanisms: inhibition of tumor angiogenesis and induction of anti-tumor immune responses.

Clinical trial (registration number): NCT03398655 (OVAL, Phase III)

Latest Clinical Developments: On March 28, Vascular Biogenics announced that the OVAL trial would continue patient enrollment, with an interim efficacy analysis expected by year-end. In the second half of this year, the company also anticipates initiating a Phase III trial in collaboration with the National Cancer Institute to evaluate the efficacy of VB-111 in combination with checkpoint inhibitors for the treatment of colorectal cancer.

VGX-3100

Companies: Inovio Pharmaceuticals, ApolloBio

Indications: High-grade squamous intraepithelial lesions (HSIL) of the cervix (Stage III) associated with HPV-16 and HPV-18 infection; precancerous lesions of the vulva and anus (Stage II).

Mechanism: VGX-3100 is the first immunotherapeutic agent for the treatment of HPV-induced cervical precancerous lesions. Leveraging ASPIRE (Antigen-Specific Immune Response) technology, the DNA plasmids of VGX-3100 target the E6 and E7 proteins on the surface of HPV 16 and HPV 18. VGX-3100 achieves intramuscular delivery via electroporation using the Cellectra® 5PSP device.

Clinical trials (registration numbers): NCT03185013 (REVEAL 1, Phase III); NCT03721978 (REVEAL 2, Phase III)

Latest Update: On May 16, Inovio partnered with QIAGEN, announcing that they would jointly develop diagnostic tests to identify patients most likely to respond to VGX-3100. On March 4, Inovio announced the initiation of the REVEAL 2 trial, with plans to submit a Biologics License Application (BLA) in 2021 for VGX-3100 as the first immunotherapy for women with cervical dysplasia. Later this year, Inovio expects to report interim Phase II results from trials NCT03603808, NCT03499795, and NCT03180684.

VM202

Companies: ViroMed, Beijing Norslandi Biotechnology, Reyon Pharmaceutical

Indications: Painful diabetic peripheral neuropathy (United States and South Korea), chronic non-healing ischemic foot ulcers in diabetes (United States), critical limb ischemia (China), amyotrophic lateral sclerosis (United States), acute myocardial infarction (South Korea)

Mechanism: The gene therapy drug VM202 can express two isoforms of HGF (hepatocyte growth factor), namely HGF728 and HGF723.

Clinical trials (registration numbers): NCT02563522 (VMNHU-003, Phase III), NCT02427464 (VMDN-003, Phase III), NCT03363165 (HI-PAD, Phase II), NCT03404024 (VMCAD-002, Phase II)

Latest Developments: In a letter to investors dated March 29, Sunyoung Kim, DPhil, CEO of ViroMed, stated that VM202 would either receive an additional indication from one of its three preclinical-stage drug pipelines or be replaced by other candidates, with these pipelines expected to reach Phase III clinical trials by 2025. On February 1, Kim indicated that ViroMed would receive the Phase III clinical trial results for VM202 in the treatment of PDPN during the summer of this year.

Zolgensma (formerly AVXS-101)

Company: Novartis subsidiary AveXis

Indications: Spinal Muscular Atrophy (SMA)

Mechanism: The non-replicating recombinant adenoviral capsid delivers a functional copy of the human SMN gene to the nucleus of the patient’s own cells. This gene fragment helps restore SMN protein secretion to normal levels.

Clinical trials (registration numbers): NCT03505099 (SPR1NT, Phase III), NCT03461289 (STRIVE-EU, Phase III), NCT03306277 (STR1VE, Phase III)

Recent Developments: On May 5, 2019, AveXis prominently announced multiple clinical trial data sets for Zolgensma. Among these, the results from the Phase III SPR1NT trial were landmark, demonstrating a significant difference in motor function between patients treated prior to symptom onset and those following the natural course of the disease.

Zynteglo (formerly LentiGlobin, BB30)

Company: Blue Bird Bio

Indications: Transfusion-Dependent β-Thalassemia (TDT)

Mechanism: The gene encoding the normal hemoglobin beta subunit (βA-T87Q-globin gene) is introduced ex vivo into hematopoietic stem cells harvested from the patient using a lentiviral vector, and these modified cells are then reinfused into the patient.

Clinical trials (registration numbers): NCT02906202 (Northstar-2 or HGB-207, Phase III), NCT03207009 (Northstar-3 or HGB-212, Phase III)

Recent Developments: On March 29, 2019, bluebird bio received a positive opinion from the European Medicines Agency (EMA) for the conditional marketing authorization of Zynteglo. The company stated that it expects to submit a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) by the end of 2019.