dm+d

Unassigned

New Medicines

Beta thalassaemia, transfusion-dependent

Information

New molecular entity
Vertex
Vertex

Development and Regulatory status

Phase II Clinical Trials
Phase II Clinical Trials
Phase II Clinical Trials
Yes
Yes
Apr 21Granted Priority Medicines (PRIME) designation in EU [8]
Nov 20Has orphan drug status in EU and US [5].
Oct 20CTX001 has been granted Regenerative Medicine Advanced Therapy (RMAT) and Rare Pediatric Disease designations from the FDA [6].
Oct 19Committee for Orphan Medicinal Products (COMP) of the EMA adopted a positive opinion, recommending the granting of orphan drug status for CTX 001, for treatment of transfusion-dependent beta thalassemia [3].
Apr 19Granted fast track status in US [3].

Category

Autologous gene-edited haematopoietic stem cell therapy, containing an autologous CD34+ human haematopoietic stem and progenitor cells (hHSPCs), modified with CRISPR-Cas9 at the erythroid lineage-specific enhancer of the BCL11A gene.
1.5% (80-90 million people) of the population of the world are carriers of beta thalassaemia [1].
Beta thalassaemia, transfusion-dependent
Intravenous infusion

Trial or other data

Nov 20CRISPR Therapeutics and Vertex report fetal hemoglobin levels rose in all seven patients after administration of CTX001 and have remained elevated for up to 15 months of follow-up. The five beta thalassemia patients last needed packed red blood cells in the first month or two after receiving CTX001, having previously more than 10 units a year, and neither of the sickle cell patients have suffered vaso-occlusive crises since treatment[4].
Jul 20Long-term follow-up study (NCT04208529) begins enrolling by invitation patients who received CTX001 in study CTX001-111 (TDT; CLIMB-111; NCT03655678) or study CTX001-121 (SCD; NCT03745287) [7].
Apr 20PI/II study (NCT03655678) recruiting [2].
Nov 19Interim results from PI/II study (NCT03655678) released from two patients, one with TDT. This patient achieved neutrophil engraftment within 33 days after the administration of CTX 001 and platelet engraftment within 37 days after infusion. At nine months after CTX001 infusion, the patient was transfusion independent and had total hemoglobin levels of 11.9g/dL, 10.1g/dL fetal hemoglobin, and 99.8%F-cells (erythrocytes expressing fetal hemoglobin) [3].
Sep 18CRISPR Therapeutics, in collaboration with Vertex Pharmaceuticals, initiates a PI/II trial to evaluate the safety and efficacy of single dose CTX 001 intravenous infusion, in patients aged between 18 to 35 years with transfusion-dependent β-thalassaemia (TDT) (CTX001-111; NCT03655678). The primary endpoint is defined as the proportion of subjects achieving transfusion reduction for at least six months, from nine to 24 months post drug infusion. 45 patients will be recruited in the USA, Germany, Canada and in the UK (Imperial College Hospital in London). Collection of primary outcome data is due to complete Feb 21 [2].

Severe sickle cell disease in patients aged ≥12 years

Information

Licence extension / variation
Vertex
Vertex

Development and Regulatory status

Phase II Clinical Trials
Phase II Clinical Trials
Phase II Clinical Trials
Yes
Yes
Nov 20CTX001 has also been granted Regenerative Medicine Advanced Therapy (RMAT) and fast track status in US for SCD [4].
Nov 20Has orphan drug status in EU and US [2].
Oct 20FDA grants rare pediatric disease status to CTX 001 for SCD [2].
Sep 20EMA grants Priority Medicines (PRIME) designation to CTX001, for the treatment of severe SCD, based on clinical data from the ongoing PI/II trial [2].

Category

Autologous gene-edited haematopoietic stem cell therapy, containing an autologous CD34+ human haematopoietic stem and progenitor cells (hHSPCs), modified with CRISPR-Cas9 at the erythroid lineage-specific enhancer of the BCL11A gene.
Sickle cell disease refers to the group of disorders that affects haemoglobin to form abnormal haemoglobin molecules (HbS). Sickle cell disease is thought to be the most common severe genetic disease in the UK and France, with 10,000-15,000 people affected. The prevalence of sickle cell disease is highest in sub-Saharan Africa [1].
Severe sickle cell disease in patients aged ≥12 years
Intravenous infusion

Trial or other data

Aug 20PI/II CLIMB-121 study is recruiting [3].
Jul 20Long-term follow-up study (NCT04208529) begins enrolling by invitation patients who received CTX001 in study CTX001-111 (TDT; CLIMB-111; NCT03655678) or study CTX001-121 (SCD; NCT03745287). [3].
Jun 20CRISPR presents data for the first patient with SCD treated with CTX001. CRISPR Therapeutics and Vertex announced initial data for this first SCD patient in Nov 19. Patient 1 with SCD experienced seven vaso-occlusive crises (VOCs) and five packed red blood cell transfusions per year (annualized rate during the two years prior to consenting for the trial) before enrolling in the clinical trial. As previously reported, the patient achieved neutrophil and platelet engraftment 30 days after CTX001 infusion. After CTX001 infusion, three SAEs occurred, none of which the PI considered related to CTX001: sepsis in the presence of neutropenia, cholelithiasis and abdominal pain; all subsequently resolved. New data presented today show that at 9 months after CTX001 infusion, the patient was free of VOCs, was transfusion independent and had total hemoglobin levels of 11.8 g/dL, 46.1% fetal hemoglobin, and F-cells (erythrocytes expressing fetal hemoglobin) of 99.7%. Bone marrow allelic editing was 81.4% at 6 months [4].
Nov 18CRISPR Therapeutics, in collaboration with Vertex Pharmaceuticals starts the PI/II CLIMB-121 trial to evaluate the safety and efficacy of single dose CTX 001 intravenous infusion, following myeloablative conditioning with busulfan, in patients with severe sSCD (CTX001-121; NCT03745287). The open label trial intends to enrol 45 patients aged 12 to 35 years in the US, Belgium, Canada, Germany, Italy and UK (Imperial College Healthcare NHS Trust, Hammersmith Hospital). Primary outcomes are proportion of subjects with HbF ≥20%, sustained for at least 3 months at the time of analysis, starting 6 months after CTX001 infusion, proportion with engraftment within 42 days, time to engraftment, adverse events, transplant-related mortality (TRM), and all-cause mortality; collection of these data is due to complete Feb 21 [3].