=Bluebird bio (BLUE), Celgene (CELG) : Myeloma therapy appears to improve in time

Celgene and bluebird bio (BLUE) report updated results from ongoing multicenter Phase 1 study of bb2121 Anti-BCMA CAR T Cell Therapy 

• Co's report updated results from the ongoing CRB-401 Phase 1 clinical study of bb2121, an investigational anti-B-cell maturation antigen (BCMA) CAR T cell therapy, in 21 patients with late-stage relapsed/refractory multiple myeloma
• Patients on study were heavily pre-treated, with a median of 7 prior therapies (range: 3 - 14):
  • 100% previously treated with lenalidomide and bortezomib
  • 91% previously treated with pomalidomide and carfilzomib
  • 71% previously treated with daratumumab
  • 29% of patients were penta-refractory (bortezomib, lenalidomide, carfilzomib, pomalidomide, daratumumab)
  • All patients had at least one prior autologous stem cell transplant

A novel therapy from Bluebird Bio Inc. and Celgene Corp. for patients nearing death from an aggressive form of blood cancer appears to get more effective over time, wiping out signs of disease in more than half of those treated in a small trial.

• A single infusion of the personalized therapy known as bb2121 generated a response in all but one of the 18 multiple myeloma patients treated at the highest dose, according to the study presented at the American Society of Hematology meeting in Atlanta. After nine months, 56 percent were in remission. That’s an improvement since May, when an earlier look at the data found 27 percent of the patients experienced a complete response.
• “Most of these patients were ready for hospice, and then this came along,” said Jesus Berdeja, director of myeloma research at Sarah Cannon Research Institute in Nashville, and one of the first doctors to use the approach. “These are just spectacular results in a patient population with a median expected survival of four months or less.”
• The treatment, known as a CAR-T, involves removing the patient’s own immune system cells, tweaking them to attack the cancer, and infusing them back into the person. The first two CAR-Ts, from Novartis AG and Gilead Sciences Inc., were approved this year in the U.S. to treat certain forms of blood cancers. The Bluebird-Celgene therapy targets a different protein, BCMA, found on myeloma and plasma cells.
• In the bb2121 study, the improvements extended as long as 15 months for patients who had previously tried all existing therapies, including stem cell transplants, and seen their cancer return.

Bluebirdbio presents New Data from Clinical Studies of LentiGlobin; shows higher in vivo vector copy numbers and hemoglobin levels  

• Co announced data from two studies of its LentiGlobin gene therapy product candidate in patients with transfusion-dependent -thalassemia
• Clinical Outcomes up to 3 Years Following LentiGlobin Gene Therapy for Transfusion-Dependent -Thalassemia in the Northstar HGB-204 Study
  • All 18 patients have =18 months follow up, with 10 completing two-year analysis. Three patients have three years of follow up (median follow-up: 27.4 months; min-max: 17.5-36.5 months).
  • Nine of ten patients with non-0/0 genotypes were free from chronic transfusions for a median of 29 months (range: 14.7-33.1 months).
    Patients with non-0/0 genotypes who were able to achieve freedom from chronic transfusions had HbAT87Q concentrations of 3.6-9.3.
    The one patient with a non-0/0 genotype who still required periodic transfusions was treated with LentiGlobin with a VCN in the lower range (VCN: 0.3 copies/diploid genome).
  • Two of eight patients with 0/0 genotypes have not received a transfusion in more than a year (16.7 months and 15.7 months). At the patients' last study visits (Month 36 and Month 18, respectively), total hemoglobin levels were 10.2 and 10.3 g/dL and HbAT87Q levels were 9.7 and 7.0 g/dL, respectively.
    Clinically meaningful reductions in transfusion volume and frequency were observed in five of the six patients with 0/0 genotypes who have continued to receive transfusions.
  • All study participants remain enrolled in the trial, and there have been no reports of graft versus host disease
• Co also announced that updated clinical results from HGB-206, the company's ongoing Phase 1 multicenter study of its LentiGlobin gene therapy product candidate in patients with severe sickle cell disease
  • Promising early results from two patients treated under amended study protocol and with refined manufacturing process show 51% and 28% anti-sickling HbAT87Q at six and nine months, respectively, exceeding levels seen previously in the HGB-206 study
  • Plerixafor mobilization and apheresis cell collection for LentiGlobin manufacture now implemented in the study, first patient treated with this method had a peripheral VCN of 2.5 copies/diploid genome at month 1