Re time-scales, if OXB`s car t shows results like above and gets FDA Breakthrough Therapy designation then again someone who knows better than most says "Rapid time to US approval. The newly empowered FDA is clearly indicating its intent to approve novel immunotherapies on the back of significant differences in overall response rate compared with standard of care coupled with interim analysis of PFS.
The EMA currently continues to request demonstrated improvements in overall
survival compared with the standard of care. However, we believe that, ultimately, the EMA will adopt the FDA’s somewhat more realistic regulatory hurdle, although it may slow EU approval in the interim.
Consequently, we anticipate that the development time for a novel immunotherapy
from late pre-clinical to approval for a first-line metastatic setting could be 5 years and as little as 3 years in the end stage setting (such as autologous T cell transfers) in the US.
Adoptive immunotherapy was one of the hottest topics at the December, 2014 ASH Meeting. Adoptive immunotherapy uses immune cells that are engineered with CARs (Chimeric Antigen Receptors) to search for and destroy tumor cells while ignoring other tissues in a cancer patient's body. In the race to get CAR-T cells to clinic, Cellectis (OTCPK:CMVLF), a French biotech under the radar of investors in the US and undervalued, is behind six other companies. But I predict Cellectis's could eventually win because of its gene editing capabilities.
Novartis (NYSE:NVS) is arguably in 1st place: the FDA gave CTL019 Breakthrough Therapy status on July 7, 2014. Novartis-funded the successful phase I/IIA trial of CTL019 which is the name given to CAR-T cells that targeted lymphocytic leukemia cell marker CD19 in this trial. The positive results were published in the October 16, 2014 issue of NEJM. The research on CTL019 in acute lymphocytic leukemia was conducted by physician-scientists from the University of Pennsylvania. David Porter, a leading U Penn researcher on CAR-T, was co-author on 16 presentations at ASH, 7 of which were focused on CAR-T. The U Penn team was first to publish successful use of CD19 CAR-T in a patient with chronic lymphocytic leukemia in New England Journal of Medicine in 2011.
Kite Pharma (NASDAQ:KITE) can arguably claim 2nd place because of its rights to the CAR-T intellectual property of researchers at NCI and NIH. Positive phase 1 results for KTE-C19, which also targets the leukemia-associated CD19 antigen, were published in the October 13, 2014 issue of The Lancet. KTE-C19 has just progressed to phase 2 for B-lymphocyte malignancies (NCT00924326). On December 22, 2014, Kite announced its NDA for FDA approval of KTE-C19. KITE-affiliated researchers also genetically engineer T-Lymphocytes to express T cell receptor (TCR), trials of which are in phase 2 (NCT01967823) and earlier for solid tumors. EGFRvIII-CAR is in phase 2 for glioblastoma (NCT01454596).
GlaxoSmithKline (NYSE:GSK) in collaboration with Adaptimmune is (I will not keep repeating the word "arguably") tied for 3rd in the race to get T-cell-based cancer therapy to clinic. Adaptimmune announced almost simultaneously with the 2014 NEJM and Lancet publications cited above, favorable results in a pilot trial of NY-ESOc259T in 8 patients with sarcoma. Adaptimmune's T-cell therapy uses TCR (T-Cell Receptors) instead of CARs. The advantage of TCR over CAR T-cells is vastly greater number of potential targets: instead of targeting only CD19 or CD20 which are pretty specific to B-lymphocytes, TCR T-cells can be directed against other tumor-specific antigens. Adaptimmune has two phase 1/2 trial for myeloma (NCT01352286 and NCT01892293), two for NY-ESOc259T (NCT01343043 and NCT01567891) in solid tumors (sarcoma and ovarian cancer), and another for NY-ESO1 in melanoma (NCT01350401). GSK/Adaptimmune have not yet published trial results, did not present any CAR-T or TCR therapy results at 2014 ASH, and have not announced an NDA submission.
AI
