Sickle Cell Disease
Update: 30 June 2021
A new analysis of data from 45 children with SCD, aged 4 to 11 years, enrolled in the open-label Phase 2a HOPE-KIDS 1 Study (GBT440-007) showed that treatment with Oxbryta (1,500 mg or weight-based equivalent dispersed in a pediatric-appropriate formulation) resulted in rapid and sustained improvements in hemoglobin.
An increase in hemoglobin of greater than 1 g/dL from baseline was observed in 47% of patients as early as two weeks and sustained through 24 weeks, consistent with results in patients ages 12 years and older in the Phase 3 HOPE Study. Concurrent improvements in markers of hemolysis were also observed. Relevant data was presented at EHA2021.
Update: 08 January 2021
No update available
Update: 05 November 2020
72-week analysis of the Phase 3 HOPE Study of Oxbryta® (voxelotor) tablets will be presented at ASH2020 in December 2020.
Update: 25 August 2020
The European Medicines Agency (EMA) has granted Oxbryta® Priority Medicines (PRIME) designation, and the European Commission (EC) designated Oxbryta as an orphan medicinal product for the treatment of patients with SCD.
The company plans to submit a Marketing Authorization Application (MAA) to EMA to treat hemolytic anemia in sickle cell disease (SCD) patients ages 12 years and older by mid-2021.
The planned MAA will include data from the Phase 3 HOPE Study and the Phase 2 HOPE-KIDS 1 Study, both of which enrolled patients at clinical sites in Europe.
The company also intends to initiate an Early Access Program in Europe for patients and physicians who may need access to Oxbryta® prior to potential marketing authorization.
USA: Discussions for the potential use of Oxbryta® (voxelotor) for the treatment of sickle cell disease (SCD) in children ages 4 to 11 years are underway under the FDA’s accelerated approval pathway.
Update: 31 May 2020
- A retrospective analysis of the HOPE 3 trial will be presented at EHA25 Congress in June.
- Access in USA slowed by COVID-19 pandemic and social distancing.
Update: 31 March 2020
No update available.
Update: 31 January 2020
In a draft report, the Institute for Clinical and Economic Review (a cost watchdog) concluded that the newly authorised sickle cell disease drugs in the US (from GBT, Novartis and Emmaus Medical) are too expensive to meet traditional cost-effectiveness measures. To fall within one measure of cost-effectiveness—below $150,000 per quality-adjusted life year—the companies would have to dramatically cut their prices.
For GBT’s Oxbryta, the cut would have to be almost 90% – a cost of $9,218 per year would be more appropriate —down from an estimated list price of $84,000 per year. And for Novartis’ Adakveo, ICER’s calculations suggested an annual cost of $25,410, less than one-third of its existing cost of $88,000 per year, as estimated by ICER.
Update: 30 June 2021
No update available
Update: 08 January 2021
Data presented at ASH2020 confirm that no new safety signals were identified in the enrolled SCD population treated with crizanlizumab, with no apparent differences between the 5.0 and 7.5 mg/kg doses in the frequency and severity of AEs. For both doses, serum crizanlizumab concentrations rose to a near maximum level shortly after infusion. Consistent with results from the SUSTAIN trial, crizanlizumab reduced from baseline the annualized rate of VOCs leading to a healthcare visit.
Source: https://ash.confex.com/ash/2020/webprogram/Paper137434.html
Update: 05 November 2020
The European Commission has approved Adakveo (crizanlizumab) as a preventive treatment for recurrent vaso-occlusive crises (VOCs) in people, 16 and older, with sickle cell disease (SCD).
The approval covers the use of Adakveo in combination with hydroxyurea (also known as hydroxycarbamide) and as a stand-alone therapy in patients for whom hydroxyurea treatment is inappropriate.
Source: https://sicklecellanemianews.com/2020/11/03/eu-approves-adakveo-to-treat-pain-crises-in-scd-patients-16-and-older/
Update: 25 August 2020
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion recommending conditional marketing authorization of Adakveo® (Crizanlizumab) for the prevention of recurrent vaso-occlusive crises (VOCs), or pain crises, in patients with sickle cell disease aged 16 years and older.
Adakveo can be given as an add-on therapy to hydroxyurea/hydroxycarbamide (HU/HC) or as monotherapy in patients for whom HU/HC is inappropriate or inadequate.
Update: 31 May 2020
- Continued access within the US.
- EMA approval expected within the second half of 2020.
Update: 31 March 2020
No update available.
Update: 31 January 2020
In a draft report, the Institute for Clinical and Economic Review (a cost watchdog) concluded that the newly authorised sickle cell disease drugs in the US (from GBT, Novartis and Emmaus Medical) are too expensive to meet traditional cost-effectiveness measures. To fall within one measure of cost-effectiveness—below $150,000 per quality-adjusted life year—the companies would have to dramatically cut their prices.
For GBT’s Oxbryta, the cut would have to be almost 90% – a cost of $9,218 per year would be more appropriate —down from an estimated list price of $84,000 per year. And for Novartis’ Adakveo, ICER’s calculations suggested an annual cost of $25,410, less than one-third of its existing cost of $88,000 per year, as estimated by ICER.
Update: 25 November 2019
- US Food and Drug Administration (FDA) approved Adakveo® (Crizanlizumab), previously known as SEG101, a targeted biologic, to reduce the frequency of vaso-occlusive crises (VOCs), or pain crises, in adult and pediatric patients aged 16 years and older with sickle cell disease.
- 45% reduction in VOCs regardless of SCD genotype and/or hydroxyurea use.
- Fewer hospitalisation days per year (4 vs 6.87)
- SUSTAIN is a randomized, multicenter, placebo-controlled, double-blind study. A total of 198 patients with any genotype of sickle cell disease (HbSS, HbSC, HbS/beta0-thalassaemia, HbS/beta+-thalassaemia, and others) and a history of 2-10 VOCs in the previous 12 months were eligible for inclusion.
Source: https://ml-eu.globenewswire.com/Resource/Download/72d8bac9-2ce7-44de-ba9e-578e5a11b8e2
Update: 30 June 2021
- Phase 1/2 (HGB-206) and Phase 3 (HGB-210) studies of LentiGlobin gene therapy for sickle cell disease (SCD) (bb1111) were placed on a temporary suspension due to a reported Suspected Unexpected Serious Adverse Reaction (SUSAR) of acute myeloid leukemia (AML) and MDS.
- The first patient was infused in HGB-210, a Phase 3 confirmatory study of LentiGlobin™gene therapy (bb1111) for adults and pediatric subjects ≥2 and ≤50 years of age with sickle cell disease (SCD).
- The analyses completed until March 2021, indicated that it is very unlikely the Suspected Unexpected Serious Adverse Reaction (SUSAR) of acute myeloid leukemia (AML) was related to the lentiviral vector. Laboratory analyses showed that the patient had significant chromosomal abnormalities and mutations in genes typically associated with the development of AML.
- The case of MDS in a patient from Group C of the Phase 1/2 HGB-206 study of LentiGlobin gene therapy for SCD has been further assessed following the review of results from additional tests. The treating investigator has concluded this is not a case of MDS and has revised the diagnosis to transfusion-dependent anemia.
- The US Food and Drug Administration (FDA) has lifted the clinical holds on the Phase 1/2 HGB-206 and Phase 3 HGB-210 studies of LentiGlobin for sickle cell disease (SCD) gene therapy (bb1111) for adult and pediatric patients with SCD.
Data of HGB-206 Group C presented at EHA2021 showed that patients with SCD maintain a median haemoglobin of ≥ 11g/dl for more than 6 months post-treatment with a complete reduction of VOC’s in up to 24 months of follow up.
EHA2021: Complete Resolution of Severe Vaso-Occlusive Events and Improved Pathophysiology with LentiGlobin Gene Therapy in Sickle Cell Disease (SCD): Ongoing Phase 1/2 HGB-206 Group C Study
Update: 08 January 2021
New data from the ongoing study of investigational LentiGlobin™ gene therapy (bb1111) show a complete elimination of severe VOEs and VOEs between six and 24 months of follow-up
Group C Phase 1/2 HGB-206 for adult and adolescent patients with sickle cell disease (SCD) results presented at ASH2020:
- 32 patients with up to 30.9 months of follow-up.
- In 22 patients with six or more months of follow-up, median levels of gene therapy- derived anti-sickling hemoglobin, HbAT87Q, contribute at least 40% of total haemoglobin.
- At last visit reported, total hemoglobin ranged from 6 – 15.1 g/dL and HbAT87Q levels ranged from 2.7 – 8.9 g/dL.
- Median HbS was 50% and remained less than 60% at all follow-up tmepoints.
- All patients in Group C were able to stop regular blood transfusions by three months post-treatment and remain off transfusions as of the data cut-off.
- 19 patients with a history of severe VOEs had a complete resolution of VOEs after Month 6.
- One patient with significant baseline SCD-related and cardiopulmonary disease died 20 months post-treatment; the treating physician and an independent monitoring committee agreed his death was unlikely related to LentiGlobin for SCD and that SCD-related cardiac and pulmonary disease contributed.
- Collaboration with Magenta Therapeutics has been announced to evaluate the utility of MGTA-145 for Mobilizing and Collecting Stem Cells in Adults and Adolescents with Sickle Cell Disease. MGTA-145 in combination with plerixafor (the so far preferred mobilization regimen) has shown in a Phase 1 study that it can rapidly and reliably mobilize high numbers of functional stem cells in a single day, without the need for G-CSF. Thus potentially allowing for safer and more efficient mobilization for gene therapy to treat sickle cell disease thus achieving safe, rapid and reliable mobilization of sufficient quantities of high-quality stem cells to improve outcomes associated with stem cell transplantation.
Source: http://investor.bluebirdbio.com/news-releases/news-release-details/treatment- investigational-lentiglobintm-gene-therapy-sickle-cell http://investor.bluebirdbio.com/news-releases/news-release-details/magenta- therapeutics-and-bluebird-bio-announce-phase-2-clinical
Update: 05 November 2020
BIOLOGICS LICENSE APPLICATION (BLA) SUBMISSION: Estimated to be completed in late-2022 as the FDA has requested the clinical data package be based on the HGB-26 study Group C cohort as well as comparable data between healthy donors, SCD patients and the commercial lentiviral vector.
EUROPEAN MEDICINES AGENCY: LentiGlobin for SCD has been granted eligibility for the EMA Priority Medicines programme and therefore PRIME designation enabling more speedy regulatory evaluations.
FOOD AND DRUG ADMINISTRATION: LentiGlobin for SCD has received orphan drug designation, fast track designation, regenerative medicine advanced therapy (RMAT) designation and rare pediatric disease designation.
Update: 25 August 2020
New data from the ongoing Phase 1/2 HGB-206 study of investigational LentiGlobin™ gene therapy for adult and adolescent patients with sickle cell disease (SCD) show a near-complete reduction of serious vaso-occlusive crises (VOCs) and acute chest syndrome (ACS). These data were presented at the Virtual Edition of the 25th European Hematology Association (EHA25) Annual Congress.
A total of 37 patients have been treated with LentiGlobin for SCD to-date in the HGB-205 (n=3) and HGB-206 (n=34) clinical studies. The HGB-206 total includes: Group A (n=7), B (n=2) and C (n=25).
Group C Efficacy Results:
- 25 patients were treated with LentiGlobin with up to 24.8 months of follow-up.
- In 16 patients with six or more months of follow-up, median levels of gene therapy-derived anti-sickling hemoglobin, HbAT87Q, were maintained with HbAT87Qcontributing at least 40% of total hemoglobin.
- At last visit reported, total hemoglobin ranged from 9.6 – 16.2 g/dL and HbAT87Qlevels ranged from 2.7 – 9.4 g/dL.
- All patients in Group C were able to stop regular blood transfusions and remain off transfusions at three months post-treatment.
- There was a 99.5% mean reduction in annualized rate of VOC and ACS among the 14 patients who had at least six months of follow-up. These patients had a median of eight events in the two years prior to treatment.
Update: 31 May 2020
- The clinical and commercial supply of ZYNTEGLO® for transfusion-dependent β-thalassemia (TDT) and SCD will be undertaken by Hitachi Chemical Advanced Therapeutics Solutions (USA) and Aptech Biopharma GmbH (Germany), both subsidiaries of Hitachi Chemical.
- Follow up data of the Phase 3 HGB-207 (TDT), HGB-212 (TDT) and HGB-206 group C (SCD) studies will be presented at the EHA25 Congress in June
Update: 31 March 2020
A new Phase 3 study of LentiGlobin for sickle cell disease (HGB-211) has been announced. This study is expected to begin enrolling patients in 2020, with a target of approximately 18 patients, ages 2-14 years with SCD and elevated stroke risk.
The primary endpoint of the study will be transcranial doppler response without transfusion.
HGB-211 is in addition to the company’s previously announced Phase 3 study (HGB-210)
Together with the phase 3 study HGB-210, HGB-211 is intended to support potential approval of LentiGlobin for SCD in pediatric patients at elevated stroke risk.
- COVID-19 EFFECTS – The company expects that the COVID-19 pandemic will shift the timing of enrollment and completion of clinical studies by at least three months and expects timing shifts to vary by clinical trial and by program.
Update: 30 June 2021
- The European Medicines Agency (EMA) granted Priority Medicines (PRIME) designation to ARU-1801. ARU-1801 was designated PRIME status based on clinical data from the MOMENTUM study, an ongoing Phase 1/2 trial of ARU-1801 in patients with severe sickle cell disease, that demonstrate meaningful, durable reductions in disease burden.
Unlike investigational gene therapies and gene editing approaches which require fully myeloablative conditioning, the unique characteristics of ARU-1801 allow it to be given with reduced intensity conditioning (“RIC”). Compared to myeloablative approaches, the lower dose chemotherapy regimen underlying RIC has the potential to reduce not only hospital length of stay, but also the risk of short- and long-term adverse events such as infection and infertility. Preliminary clinical data from the MOMENTUM study, an ongoing Phase 1/2 trial of ARU-1801 in patients with severe sickle cell disease, demonstrate continuing durable reductions in disease burden.
- Three patients with sickle cell disease who received the investigational gene therapy ARU-1801 achieved and maintained normal hemoglobin levels, according to early results of a phase 1/phase 2 trial.
Update: 08 January 2021
No update available
Update: 05 November 2020
Data will be presented at ASH2020 in December 2020 from the MOMENTUM study – an open-label Phase 1/2 clinical trial examining ARU-1801 as a one-time potentially curative gene therapy for individuals with sickle cell disease (SCD).
Unlike other investigational gene therapies that require fully myeloablative conditioning, ARU-1801 is given with reduced intensity conditioning (RIC), which is a lower dose chemotherapy.
Update: 25 August 2020
No update available.
Update: 31 May 2020
No update available.
Update: 31 March 2020
No update available.
Update: 31 January 2020
The U.S. Food and Drug Administration (FDA) granted rare pediatric disease designation to ARU-1801, an experimental gene therapy for the treatment of sickle cell disease (SCD) and β-thalassaemia.
This designation means eligibility for a priority review voucher once the FDA approves a biologics license application for ARU-1801.
Focus on delivering a modified version of the fetal haemoglobin gene, through a viral virus called lentivirus — optimized to enhance the protein’s natural oxygen-carrying ability and anti-sickling properties.
Update: 30 June 2021
New data has been presented at EHA2021 on the investigational CRISPR/Cas9-based gene-editing therapy, CTX001, showing a consistent and sustained response to treatment:
- Follow-up data of 4 TDT patients infused with CTX0001 was presented. All patients demonstrated increases in total haemoglobin and HbF. No patient reported any VOC’s for the duration of follow-up (19.2 months).
Source: EHA2021
CRISPR gene editing (SCD) – UCSF Benioff Children’s Hospital Oakland
Update: 30 June 2021
The U.S. Food and Drug Administration approved the start of the first clinical trial of CRISPR_SCD001, the first non-viral and CRISPR/Cas9-based gene editing therapy for SCD.
CRISPR_SCD001 uses the power of the CRISPR-Cas9 gene editing system to replace the mutated HBB gene in a patient’s hematopoietic stem cells with a healthy version.
Unlike other investigational gene editing approaches for sickle cell, CRISPR_SCD001 delivers the CRISPR-Cas9 machinery to cells without relying on a virus as a transport agent. Its method, called electroporation, uses electrical pulses to create temporary pores in cell membranes that allow for the gene-editing tool to enter.
Phase 1/2 trial, up to nine patients with severe SCD, ages 12–35 over 4 years.
CRISPR gene editing (SCD) – GPH101
Update: 30 June 2021
The investigational gene editing therapy GPH101 has been approved by the FDA for a Phase 1/2 clinical trial. The new, open-label trial, called CEDAR, is designed to evaluate the safety and pharmacological properties of GPH101, as well as its preliminary efficacy in adults and adolescents with severe SCD.
GPH101 leverages the power of the CRISPR-Cas9 gene-editing tool, along with a natural DNA repair mechanism, to remove the mutation in the beta-globin (HBB) gene that causes SCD, and replace it with the correct DNA sequence.
Update: 08 January 2021
New data has been presented at ASH2020 on the investigational CRISPR/Cas9- based gene-editing therapy, CTX001, showing a consistent and sustained response to treatment:
- 6 patients with SCD have been dosed with CTX001.
- 3 patients have reached at least 3 months follow up after CTX001 dosing. All three patients showed a similar pattern of response, with rapid and sustained increases in total hemoglobin and fetal hemoglobin, as well as elimination of VOCs for a duration between 3 – 15 months post infusion. Total hemoglobin in the range of 5 – 13.2 g/dL and fetal hemoglobin levels from 31.3% to 48.0%.
- There were no SAEs considered related to CTX001, and the majority of non- serious adverse events were considered mild to moderate.
Source: https://news.vrtx.com/press-release/crispr-therapeutics-and-vertex-present-new- data-investigational-crisprcas9-gene
Update: 05 November 2020
- The European Medicines Agency (EMA) has granted Priority Medicines (PRIME) designation to CTX001.
- Data from five patients with three months to 15 months of follow-up after CTX001 infusion in the ongoing Phase 1/2 CLIMB-111 trial in transfusion-dependent beta thalassemia (TDT) and data from two patients with three months and 12 months of follow-up in the ongoing Phase 1/2 CLIMB-121 trial in severe sickle cell disease (SCD) will be presented at ASH2020 to be held in December 2020.
- Additional data will be presented at ASH, including longer-duration follow-up data for the patients included in the abstract and data for additional patients with greater than three months of follow-up.
Update: 25 August 2020
Data presented at EHA25 Annual Congress of the CLIMB-121 Trial in Severe Sickle Cell Disease reflect longer-duration follow-up data for the first patient with SCD treated with CTX001.
Patient 1 with SCD experienced 7 vaso-occlusive crises (VOCs) and 5 packed red blood cell transfusions per year before enrolling in the clinical trial.
The patient achieved neutrophil and platelet engraftment 30 days after CTX001 infusion.
New data 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.
CLIMB-SCD-121: Dosed a total of 2 patients and both patients have successfully engrafted. The trial is also now open for concurrent dosing after successful dosing and engraftment of these first two patients.
Update: 31 May 2020
- Regenerative Medicine Advanced Therapy (RMAT) designation has been granted by the FDA.
- RMAT seeks to fasten the development & review of new therapies, allowing for priority review and possibly faster approval by the FDA.
- CTX001 uses CRISPR-Cas9 gene editing tool to produce higher levels of fetal haemoglobin in RBCs. Increased levels of fetal haemoglobin are expected to lower the frequency of vaso-occlusive crises (VOCs).
- Preliminary data from the Phase 1/2 CLIMB-SCD-121 trial (NCT03745287), which is assessing the safety and effectiveness of a single dose of CTX001 in patients with severe SCD, has shown that the therapy safely increased the levels of fetal hemoglobin in the first patient dosed, effectively preventing the occurrence of VOCs.
Update: 31 March 2020
No update available.
Update: 30 June 2021
The U.S. Food and Drug Administration (FDA) has cleared the initiation of the safety phase of the EDIT-301 clinical trial, and patients can be dosed. EDIT-301 is an experimental, ex vivo gene editing cell medicine in development for the treatment of sickle cell disease.
Update: 08 January 2021
No update available
Update: 05 November 2020
- The U.S. Food and Drug Administration (FDA) has granted Rare Pediatric Disease (RPD) designation for EDIT-301.
- An investigational new drug application (IND) for EDIT-301 is planned to be filed by the end of 2020.
Update: 25 August 2020
No update available.
Update: 31 May 2020
Editas Medicine is developing EDIT-301 using Cas12a (Cpf1), a proprietary enzyme, as a potentially best-in-class medicine to treat sickle cell disease and β-thalassaemia. Preclinical in vivo toxicology studies are in progress and the Company expects to file to the FDA for Investigational New Drug (IND) for sickle cell disease by the end of 2020.
Update: 30 June 2021
No update available
Update: 08 January 2021
No update available
Update: 05 November 2020
Patient enrolment has begun at MSKCC.
Source: https://www.mskcc.org/cancer-care/clinical-trials/20-411
Update: 25 August 2020
No update available.
Update: 31 May 2020
No update available.
Update: 31 March 2020
The FDA has authorised the start of a Phase 1/2 clinical trial testing a genome editing-based therapy for adults with severe complications of sickle cell disease (SCD).
The clinical trial uses CRISPR/Cas9 genome-editing technology to edit the genome to increase the development of fetal haemoglobin, thus increasing the efficiency of oxygen transportation in the body.
Animal studies have suggested an increase of up to 30% of fetal haemoglobin in red blood cells.
Update: 30 June 2021
BIVV003, an investigational ex vivo gene-edited cell therapy product candidate currently being evaluated for the treatment of sickle cell disease in the Phase 1/2 PRECIZN-1 study has been granted EMA Orphan Designation. The decision was based on early data from three patients that had 52 weeks, 13 weeks, and 29 days of follow-up, respectively.
Update: 08 January 2021
No update available
Update: 05 November 2020
No update available
Update: 25 August 2020
No update available
Update: 31 May 2020
- Enrolment of SCD patients continues.
- Data from the study will be presented at a future date.
Update: 31 March 2020
No update available.
Update: 31 January 2020
Data presented at 61st Annual Meeting of the American Society of Hematology revealed that >90% of edited cells were biallelic, displaying on average 27-38% more HbF% despite variation in donor baseline levels.
Editing resulted in a 3-fold HbF increase.
Update: 30 June 2021
- Preclinical data with FTX-6058 showed an increase in HbF levels up to approximately 30% of total haemoglobin.
- Fulcrum has initiated a Phase 1 trial with FTX-6058 in healthy adult volunteers. Dosing has been initiated in the randomized, double-blind, placebo-controlled, multiple ascending dose (MAD) cohorts of the trial. Dosing continues in the single ascending dose (SAD) portion.
- The company anticipates sharing data from this Phase 1 trial in mid-2021 and initiating a clinical trial in sickle cell patients by the end of 2021.
Update: 08 January 2021
No update available
Update: 05 November 2020
An Investigational New Drug application is now in effect in the USA for a Phase 1 trial in healthy adult volunteers to investigate FTX-6058 for sickle cell disease patients.
FTX-6058 is a small molecule designed to increase fetal haemoglobin.
The Phase 1 trial will evaluate the safety, tolerability, and pharmacokinetics of FTX-6058 and will be comprised of four parts.
- Part A will be a randomized, double-blind, placebo-controlled, single ascending dose (SAD) study in up to six cohorts.
- Part B will be a randomized, double-blind, placebo-controlled, multiple ascending dose (MAD) study in up to four cohorts dosed once daily for 14 days.
- Part C will be an open-label pilot food effect study in subjects randomized to take FTX-6058 with and without a high-fat meal, and
- Part D will be an open-label study to evaluate the potential of FTX-6058 to induce CYP3A – an enzyme that helps humans metabolize or digest drugs.
Update: 30 June 2021
Data from the presented at EHA2021 showed that 88% of patients (7/8) have achieved a hemoglobin increase of more than 1 g/dL, with a mean hemoglobin increase of 1.5 g/dL after the treatment for at least two weeks.
However, two patients have developed serious adverse events. The one with vaso-occlusive crisis and acute chest syndrome were found to be unrelated to the treatment by the trial investigator.
The enrolment is currently underway for the company’s Phase 2/3 Hibiscus Study for FT-4202 in patients with SCD.
Update: 08 January 2021
- Orphan Drug Designation provided by European Commission
- Data presented at ASH2020 shows that a clinical proof-of-concept in patients with sickle cell disease (SCD) has been observed in the ongoing randomized, placebo-controlled, multi-center Phase 1 trial of FT-4202.
- In a cohort of nine patients, six of seven patients (86%) who received FT-4202 achieved a hemoglobin increase of greater than 1 g/dL from baseline with once- daily dosing at 300 mg for 14 days.
- The results are based on 9 patients with SCD randomly assigned to receive a single oral dose of 300 mg daily of FT-4202 or placebo for 14 days. The data show that, from baseline, in patients receiving FT-4202:
- 6 of 7 achieved a > 1 g/dL increase in hemoglobin (Hb); median 1.2 g/dL increase (range 0, 2.3 g/dL);
- 2,3-DPG levels were reduced, thus increasing oxygen affinity and decreasing sickle hemoglobin polymerization;
- Adenosine triphosphate (ATP) levels were increased resulting in improved RBC function and reduced hemolysis;
- 7 of 7 achieved a reduction in reticulocytes; median 60% decrease (range-39%, -81%);
- 6 of 7 achieved a reduction in lactate dehydrogenase (LDH); median 36% decrease (range +18%, -57%); and
- 7 of 7 achieved a reduction in bilirubin; median 35% decrease (range -7%,-63%).
Sources: https://www.pharmaceutical-business-review.com/news/forma-therapeutics-sickle/
https://ir.formatherapeutics.com/news-releases/news-release-details/forma- therapeutics-presents-clinical-proof-concept-data-62nd
Update: 05 November 2020
Clinical data on 9-12 patients from the multiple ascending dose cohort of a randomized, multi-center, placebo-controlled Phase 1 trial of FT-4202 in people living with sickle cell disease (SCD) will be shared at the ASH2020 Meeting in December 2020.
Update: 25 August 2020
Data from the Phase 1 single and multiple ascending dose study of FT-4202, in healthy and sickle cell disease subjects has shown a favorable safety profile and the expected biological effects, providing preliminary support of efficacy. The data were presented at the EHA25 Annual Congress.
A Global Phase 2/3 study in SCD patients is planned for late 2020.
Source: https://www.cybergrants.com/pls/cybergrants/ao_login.login?x_gm_id=5084&x_proposal_type_id=40104
Update: 31 May 2020
Granted Orphan Drug designation by FDA.
Update: 31 March 2020
- FT-4202 is a small chemical molecule that is designed to bind to PKR in the RBCs and increases its activity. This increases the affinity of haemoglobin for oxygen in the sickled RBCs, and helps them deliver more oxygen to different tissues and organs in the body. When oxygen affinity increases, the sickling of the RBCs decreases. FT-4202 could, also alleviate other symptoms of SCD like vaso-occlusive crises.
- A Phase 1 randomized, placebo-controlled, double-blind, single- and multiple-ascending dose study is assessing the safety, pharmacokinetics (movement in the body), and pharmacodynamics (effects on the body) of FT-4202 first in healthy volunteers and then in SCD patients.
- With a favourable safety profile, the trial is currently recruiting SCD patients in the U.S. to conduct a planned second part; It is expected to finish by September 2020.
- Given fast track and rare pediatric disease designations by the U.S. Food and Drug Administration (FDA).
Update: 30 June 2021
No update available.
Update: 08 January 2021
No update available
Update: 05 November 2020
Imatinib has been shown to drastically increase HbF as published in the Journal of Clinical Medicine, “Large-Scale Drug Screen Identifies FDA-Approved Drugs for Repurposing in Sickle-Cell Disease.“
Thus, Imatinib is a strong candidate for repurposing towards use in SCD due to the strong effects on HbF expression, low cytotoxicity, and safe history of use in humans (imatinib also known as Glivec (EU) or Gleevec (USA) has originally been authorised for blood cancers and solid tumors to control cell division)
https://www.mdpi.com/2077-0383/9/7/2276/htm
https://www.ema.europa.eu/en/medicines/human/EPAR/glivec
Update: 25 August 2020
No update available
Update: 31 May 2020
- A phase I clinical trial in the US aims to investigate whether imatinib (a SYK tyrosine kinase inhibitor) can reduce the expression of SCD symptoms (e.g. RBC deformability, adhesion / stickiness, etc.) and thus painful crises in patients with SCD.
- The hypothesis focuses on the connection between the increased oxidative stress levels found in SCD and the subsequent increase of tyrosine phosphorylation of band 3 which in turn is responsible for some of the SCD symptoms. Inhibiting or blocking the increase of tyrosine phosphorylation band 3 with imatinib fewer complications in SCD patients may occur.
- Still in early phase I, the study will enroll 48 pediatric patients who have not yet undergone transfusion
Update: 30 June 2021
Data presented at EHA2021 from the phase 2a clinical trial for the safety and efficacy of IMR-687 in 93 SCD patients showed that:
- IMR-687 was well-tolerated as a monotherapy and in combination with hydroxyurea
- Lower and less frequent rates of VOC: Patients treated with IMR-687 reported at least 169 days between the onset of treatment and their first VOC (compared to 87 days reported by the placebo group).
Update: 08 January 2021
Two case reports from the ongoing IMR-687 Phase 2a open label extension (OLE) clinical trial in adult patients with sickle cell disease (SCD) were presented at ASH2020:
- Patients were treated for more than 6 months, demonstrating higher HbF percentage and F-cell increases compared to baseline when treated with IMR-687, as a monotherapy or in combination with stable dose hydroxyurea (HU).
- Treatment with IMR-687 was also associated with improvements in clinical outcomes and red cell markers, including hemoglobin (Hb) levels and measures of haemolysis in both patients.
- IMR-687 was well tolerated by both patients.
Sοurce: https://ir.imaratx.com/news-releases/news-release-details/imara-presents-imr-687- phase-2a-open-label-extension-case
Update: 05 November 2020
- The European Commission has granted orphan drug designation to IMR-687 for SCD.
- IMR-687 had already received the designations of orphan drug, fast track, and rare pediatric diseasefrom the S. Food and Drug Administration for SCD.
Update: 25 August 2020
Data from the ongoing Phase 2a clinical trial of IMR-687 in adult patients with sickle cell disease (SCD) were presented at the 25th European Hematology Association (EHA) Annual Congress. The data from demonstrated that IMR-687, an oral, once-a-day treatment was safe and well tolerated as a monotherapy and in combination with hydroxyurea (HU). In the higher dose cohort, IMR-687 monotherapy showed an increase in fetal hemoglobin (HbF), as well as a dose-dependent increase in HbF levels in adult patients with SCD.
Ardent IMR-687 Phase 2b Clinical Trial: A global, randomized, double-blind, placebo-controlled, multicenter Ardent Phase 2b clinical trial will enroll approximately 99 adult patients with sickle cell disease (SCD). The planned primary efficacy objective is to evaluate the proportion of all patients with fetal hemoglobin (HbF) response, defined as an increase of 3% in HbF.
- First patient dosed.
Update: 31 May 2020
- Interim data from the ongoing Phase 2a study of IMR-687 in patients with SCD will be presented at EHA25 Congress to be held in June.
- Enrolment in the trial was completed in January 2020.
- Final data will be announced in the fourth quarter of 2020.
Update: 31 March 2020
Based on the interim Phase 2a data, the initiation of two Phase 2b studies in the first half of 2020 are expected. One in in sickle cell disease and the other in beta thalassemia. Preliminary data from both studies are expected in the first half of 2021.
Sources: https://www.fool.com/investing/2020/03/05/hematology-focused-biotech-imara-to-ipo-soon.aspx
Update: 30 June 2021
Agios is initiating its pivotal Phase 2/3 study with mitapivat in sickle cell disease by year-end 2021.
Update: 08 January 2021
- FDA Orphan Drug Designation Granted to Mitapivat for Treatment of Sickle Cell Disease
- Data on safety and tolerability were presented at ASH2020:
- 6/11 evaluable patients achieved a hemoglobin increase of ≥1.0 g/dL from baseline. The mean hemoglobin increase among all efficacy evaluable patients was 1.3 g/dL,
- All 11 evaluable patients have received three ascending dose levels of mitapivat (5 mg BID, 20 mg BID, 50 mg BID) for two weeks’ duration, respectively, and of these, three patients have received an additional ascending dose of 100 mg BID for two All underwent a 12- or 15-day drug taper after completing the dosing.
- Trial may enrol up to 25 patients.
- A Phase 3, global, pivotal study of mitapivat in sickle cell disease is expected to initiate in 2021.
Sources: https://investor.agios.com/news-releases/news-release-details/agios-announces-fda- orphan-drug-designation-granted-mitapivat-0
https://investor.agios.com/news-releases/news-release-details/agios-announces- updated-data-phase-1-study-mitapivat-first-class
Update: 05 November 2020
Safety and tolerability data will be presented at the 62nd ASH Meeting in December 2020.
Update: 25 August 2020
The ongoing Phase 1 study, which can enroll up to 25 patients, is evaluating the efficacy, safety, pharmacokinetics and pharmacodynamics of treatment with Mitapivat in adults with sickle cell disease.
6 patients have received three ascending dose levels of Mitapivat. 8 patients have completed all planned dose levels. 1 patient discontinued within the first week due to a pre-existing condition. The primary endpoint of the study is safety and tolerability as assessed by frequency and severity of adverse events and laboratory parameters. Secondary endpoints included changes in hemoglobin, markers of hemolysis, 2,3-DPG and ATP levels and HbS polymerization.
Clinical proof-of-concept has been established based on a preliminary analysis in the Phase 1 trial of Mitapivat (AG-348) in patients with sickle cell disease. The study is being conducted in collaboration with the National Institutes of Health (NIH) as part of a cooperative research and development agreement.
7/8 (88%) patients who completed all planned dose levels of Mitapivat experienced a Hb increase, with 5/8 patients (63%) achieving a hemoglobin increase of ≥1.0 g/dL and decreases in both sickling and HbS polymerization, further supporting the proposed mechanism of action.
Update: 31 May 2020
- A phase II proof-of-concept trial of mitapivat in sickle cell disease is being run under a Cooperative Research and Development Agreement (CRADA) with the U.S. National Institutes of Health(NIH).
- New enrollment is paused as a result of the COVID-19 pandemic but remains on track for mid-2020.
- Data are expected to be submitted by NIH for presentation at the American Society of Hematology (ASH) Annual Meeting in December.
Update: 30 June 2021
No update available
Update: 08 January 2021
No update available
Update: 05 November 2020
No update available
Update: 25 August 2020
No update available.
Update: 31 May 2020
No update available.
Update: 31 March 2020
No update available.
Update: 31 January 2020
No update available
Update: 25 November 2019
- The Phase 3 RESET trial testing the effectiveness and safety of Rivipansel(GMI-1070), to treat vaso-occlusive crisis (VOC) in hospitalized patients with sickle cell disease (SCD), failed to reach both its primary and secondary goals, top-line study results show.
Update: 27 September 2019
Granted marketing authorisation in the EU.
Xromi is a hybrid medicine of Hydrea which has been authorised in the EU since 29 May 1986. Xromi contains the same active substance as Hydrea but is authorised for a different indication. Hydrea is authorised for the treatment of certain cancers.
With new supportive data, Xromi is intended for the prevention of vaso-occlusive complications of sickle cell disease in patients over 2 years of age, to be available as a 100 mg/ml oral solution.
The active substance of Xromi is hydroxycarbamide.
Sources: https://www.ema.europa.eu/en/medicines/human/EPAR/xromi
https://www.ema.europa.eu/en/medicines/human/summaries-opinion/xromi
Update: 30 June 2021
- The Saudi Food and Drug Authority (SFDA), in Saudi Arabia, will review the oral medication Endari(L-glutamine) for treating sickle cell disease (SCD). Given that the SFDA’s review process typically takes 12 to 18 months, a decision is not expected before mid-to late-2022. Meanwhile, Endari will be available to eligible SCD patients in the Kingdom of Saudi Arabia on an early access basis to address an unmet medical need.
- The medicine gained approval in Israel in June 2020.
- Endari has been approved in the USA since 2017 to treat severe SCD complications in adults and children, ages 5 and older.
- In the face of a negative opinion from the European Medicines Agency (EMA) over efficacy doubts, Emmaus Life Sciences has withdrawn its marketing application in 2019.
- As the company seeks other regulatory pathways within the EMA, Xyndari (EU name) is currently, available through early access programs in a number of European Union member states, as well as in Turkey, the Middle East, and South America.
