Bristol-Myers CAR T successful in pivotal lymphoma study, but with four deaths

Bristol-Myers Squibb (NYSE:BMY) announces positive results from a pivotal open-label Phase 1 clinical trial, TRANSCEND-NHL-001, evaluating CAR T therapy lisocabtagene maraleucel (liso-cel) (JCAR017) in patients with relapsed/refractory large B-cell lymphomas, a Breakthrough Therapy indication. The data were presented at ASH in Orlando.

The study met the primary and secondary endpoints. Specifically, the overall response rate (ORR) was 73% (n=187/256), including a 53% (n=136/256) complete response rate (primary endpoint).

Median duration of response was not reached at a median follow-up of 12 months. Median progression-free survival was 6.8 months and median overall survival was 21.1 months (secondary endpoints).

On the safety front, the most frequent serious/life-threatening/fatal treatment-related adverse events were neutropenia (60%), anemia (38%) and thrombocytopenia (27%). The incidence of any grade cytokine release syndrome (CRS) was 42% (n=113/269) with a median onset of five days post infusion. The rate of serious or higher CRS was 2% (n=6/269). The rate of neurologic events (NEs) was 30% (n=80/269), including a 10% incidence of serious or higher NEs.

There were four deaths (diffuse alveolar damage, pulmonary hemorrhage, multiple organ dysfunction syndrome or cardiomyopathy) related to liso-cel. There were three deaths (fludarabine leukoencephalopathy, septic shock and progressive multifocal leukoencephalopathy) considered unrelated to liso-cel.

The company expects to complete the filing of its U.S. marketing application this month.

#ASH19

https://seekingalpha.com/news/3524626-bristol-myers-car-t-successful-in-pivotal-nhl-study-four-deaths

Bluebird bio LentiGlobin gene therapy has significant effect in sickle cell study

New data from an ongoing open-label Phase 1/2 clinical trial, HGB-206, evaluating bluebird bio’s (NASDAQ:BLUE) LentiGlobin gene therapy in sickle cell disease (SCD) patients showed a significant treatment benefit. The results were presented at ASH in Orlando.

Participants in Group C (17 treated thus far) continue to produce high levels of gene therapy-derived anti-sickling hemoglobin, HbA^T87Q, accounting for at least 40% of total hemoglobin in those with six or more months of follow-up. Cherry-picking the data, nine patients with at least six months of follow-up who had at least four vaso-occlusive crisis (VOC) or acute chest syndrome (ACS) events in the prior two years experienced a 99% reduction in annualized rate of VOC and ACS with no reports of such events up to 21 months post-infusion.

At data cutoff, 78% (n=7/9) of patients in Groups A & B had not required red blood cell transfusions post treatment.

No new safety signals were observed.

LentiGlobin is designed to add functional copies of a modified form of the β-globin gene (β^A-T87Q-globin gene) into a patient’s own hematopoietic (blood) stem cells. Once patients have the β^A-T87Q-globin gene, their red blood cells can produce anti-sickling hemoglobin which decreases the proportion of sickled hemoglobin and lessens SCD complications.

A long-term follow-up study, LTF-303, in SCD is ongoing with an estimated completion date of March 2031.

A Phase 3 trial, HGB-210, should commence next quarter.

$ASH19

https://seekingalpha.com/news/3524627-bluebird-bios-lentiglobin-gene-therapy-shows-significant-effect-in-scd-study

Roche candidates show promise in treatment-resistant lymphoma

Roche (OTCQX:RHHBY) unit Genentech announces encouraging data from early-stage studies of two investigational T-cell engaging bispecific antibodies, mosunetuzumab and CD20-TCB, in treatment-resistant non-Hodgkin lymphoma (NHL) patients, including some who failed to respond to CAR T therapy. The results were presented at ASH in Orlando.

An open-label dose-escalation Phase 1 trial, GO29781, is evaluating mosunetuzumab alone and in combination with Tecentriq (atezolizumab) in NHL and CLL patients. In NHL patients, the overall response rate (ORR) was 63% (n=42/67) in those with slow-growing cancer and 37% (n=46/124) in those with aggressive cancer. The complete response rates were 43% and 19%, respectively. In patients refractive to CAR T therapy, the ORR was 39% (n=7/18) including four (22%) complete responders.

On the safety front, the rate of cytokine release syndrome was 29%, most (28%) mild or moderate. The rate of serious adverse neurological events was 4%.

Another open-label dose-escalation Phase 1, NP30179, is evaluating CD20-TCB alone and in combination with Gazyva (obinutuzumab) in relapsed/refractory B-cell NHL patients. The ORR in subjects receiving the combo was 54% (n=15/28), including 13 (46%) complete responders. The complete response rate was 67% (n=4/6) in a subset of follicular lymphoma patients and 41% (n=9/22) in a subset of patients with aggressive NHL.

On the safety front, the most common (68%) treatment-related adverse event was cytokine release syndrome (n=19/28), most being low grade.

Development is going.

https://seekingalpha.com/news/3524628-roche-candidates-show-promising-action-in-treatment-resistant-nhl

Half of lymphoma patients alive 3 years after Gilead cell therapy treatment

Nearly half of lymphoma patients treated with Gilead Sciences Inc’s Yescarta were alive at least three years after a one-time infusion of the CAR-T cell therapy, according to data presented on Saturday.

Out of 101 patients teated with Yescarta for an aggressive blood cancer known as refractory large B-cell lymphoma in the study, 47 were still alive at least three years later, the data presented at the American Society of Hematology meeting in Orlando showed.

“We are delivering towards our goal of potentially life-saving therapy for many patients who previously faced limited treatment options,” Christi Shaw, chief executive of Gilead’s Kite unit, said in a statement. Gilead bought Kite in 2017 for $12 billion to acquire Yescarta.

Sales of Yescarta, which won U.S. approval in October 2017 and carries a list price of $373,000, were slow to take off due to a range of issues, including high hospital costs and a complicated manufacturing process.

Global sales for the first nine months of 2019 were $334 million. Analysts forecast annual sales reaching $1 billion by 2022 and climbing from there, according to Refinitiv data.

Yescarta belongs to a new class of cancer treatments called CAR-T therapy, seen as potentially revolutionary due to their promise of long-term survival with a one-time treatment for certain deadly blood cancers, such as relapsed or refractory large B-cell lymphomas.

The treatment is made by harvesting T-cells from a patient’s own immune system. They are then engineered to more efficiently recognize and attack the cancer cells before being infused back into the patient.

Yescarta competes with Kymriah from Novartis AG, while several companies also are developing CAR-T treatments, including some that aim to be off-the-shelf rather than patient specific.

Gilead also reported that steroids given to one group of patients helped reduce the risk of a serious complication associated with CAR T therapy called cytokine release syndrome (CRS), which can cause a range of dangerous symptoms including fever and neurological problems.

“Early steroid intervention has the potential to reduce the rate of severe CRS and neurologic events while appearing to maintain comparably impressive efficacy for Yescarta,” Dr. Max Topp, a researcher from University Hospital of Wuerzburg, Germany who worked on the study, said in a statement.

https://www.reuters.com/article/us-gilead-sciences-lymphoma/half-of-lymphoma-patients-alive-three-years-after-gilead-cell-therapy-treatment-study-idUSKBN1YB0JT

Biotech week ahead, Dec. 9

Biotech stocks went back and forth but managed to end the week with a gain. As usual, some stocks swung wildly in reaction to catalysts, primarily clinical readouts.

Aurinia Pharmaceuticals Inc AUPH 2.93% more than doubled in a single session after its lead drug aced a pivotal trial in lupus nephritis. Meanwhile, SAGE Therapeutics Inc SAGE 7.11% saw more than half of its market value wiped out due to disappointing late-stage data for its depression drug.

Here are the key catalysts for the unfolding week.

Conferences

American Epilepsy Society, or AES, 2019 Annual Meeting – Dec. 6-10 in Baltimore, Maryland
61st American Society of Hematology, or ASH, Annual Meeting – Dec. 7-10 in Orlando, Florida
San Antonio Breast Cancer Symposium, or SABCS, 2019 – Dec. 10-14 in San Antonio, Texas
European Society of Medical Oncology, or ESMO, Immuno-Oncology Congress – Dec. 11-14, in Geneva, Switzerland

PDUFA Dates

The FDA is set to rule on Amgen, Inc.’s AMGN 0.15% ABP 710, a biosimilar to Johnson & Johnson’s JNJ 0.55% Remicade, which has been approved for multiple indications such as Crohn’s disease, ulcerative colitis, rheumatoid arthritis, psoriatic arthritis, plaque psoriasis and ankylosing spondylitis. The BsUFA date is set for Saturday.

Adcom Calendar

FDA’s Cardiovascular and Renal Drugs Advisory Committee will discuss Tuesday Correvio Pharma Corp’s CORV 39.81% NDA for Brinavess, or vernakalant HCl solution, ahead of the Dec. 24 PDUFA action date.

Clinical Readouts

ASH Presentations

Sunday

Orchard Therapeutics PLC – ADR ORTX 4.27% – Phase 1/2 data for OTL-103 in Wiskott-Aldrich syndrome

TG Therapeutics Inc common stock TGTX 7.29% – Phase 1/2 data for umbralisib in combination of AbbVie Inc ABBV 0.37%‘s Venclexta in chronic lymphocytic leukemia

GENMAB A/S/S ADR GMAB 1.33%: initial Phase 1 data for HexaBody-DR5/DR5 in solid tumors

Morphosys Ag MOR 1.42%: Phase 1 data for tafasitamab in diffuse large B-cell lymphoma

Uniqure NV QURE 2.28%: Phase 2b data for AMT-061 in hemophilia B

Autolus Therapeutics Ltd – ADR AUTL 0.27% – Phase 1 data for AUT02 in relapsed or refractory multiple myeloma

Bristol-Myers Squibb Co BMY 0.72%: updated Phase 1 data for liso-cel in chronic lymphocytic leukemia

Actinium Pharmaceuticals Inc ATNM 6.74%: Phase 1 data for actimab-A in combination with CLAG-M in relapsed or refractory acute myeloid leukemia

Portola Pharmaceuticals Inc PTLA 3.03%: interim Phase 2a data for cerdulatinib in refractory non-Hodgkin lymphoma and chronic lymphocytic leukemia

Rocket Pharmaceuticals Inc RCKT 13.47%: Phase 1 data for RP-L102 in Fanconi anemia

Fortress Biotech FBIO 7.01% and Mustang Bio Inc MBIO 0.52%: Phase 1 data for MB-106 in B-cell non-Hodgkin lymphoma and chronic lymphocytic leukemia

PDS Biotechnology Corp PDSB 12.8%: Phase 1 data for PDS0101 in head and neck cancer/human papillomavirus 16 infection

Sunesis Pharmaceuticals, Inc. SNSS 8.57%: Phase 1/2 data for vecabrutinib in advanced B-cell malignancies

Alpine Immune Sciences Inc ALPN 5.14%: Phase 1 data for ALPN-101 in healthy volunteers

Kura Oncology Inc KURA 2.63%: Phase 2 data for tipifarnib in relapsed or refractory peripheral T-cell lymphoma

Beigene Ltd BGNE 1.21%: Phase 3 data for zanubrutinib in first-line chronic lymphocytic leukemia or small lymphocytic leukemia

Autolus Therapeutics Ltd – ADR AUTL 0.27%: Phase 1 data for AUT03 in acute lymphoblastic leukemia

Blueprint Medicines Corp BPMC 5.26%: initial Phase 2 data for avapritinib in indolent and smoldering systemic mastocytosis

Eli Lilly And Co LLY 0.16%: Phase 1/2 data for LOXO-305 in refractory chronic lymphocytic leukemia, small lymphocytic lymphoma, non-Hodgkin’s lymphomas

Imv Inc IMV 4.14%: Phase 2 data for DPX-Survivac and Merck & Co., Inc. MRK 0.09%‘s Keytruda in diffuse large cell lymphoma

Monday

• bluebird bio Inc BLUE 1.53%: Phase 3 data for lentiglobin – HGB-212 in transfusion-dependent thalassemia and the β0/β0genotype and lentiglobin – HGB-207 in non-β0/β0 transfusion-dependent thalassemia
• Magenta Therapeutics Inc MGTA 2.39%: Phase 2 data for MGTA-456 in acute lymphoblastic leukemia
• CELYAD SA/ADR CYAD 5.14%: Phase 1 data for CYAD-01 in solid and hematologic cancers; Phase 1 data for CYAD-01 and chemotherapy in acute myeloid leukemia or myelodysplastic syndrome
• Achillion Pharmaceuticals, Inc. ACHN 0.33% and Alexion Pharmaceuticals, Inc. ALXN 6.02%: danicopan in paroxysmal nocturnal hemoglobinuria
• Seattle Genetics, Inc. SGEN 0.29%: Phase 1/2 data for ST-400 in beta thalassemia
• Agios Pharmaceuticals Inc AGIO 2.15%: Phase 2 data for AG-348 in pyruvate deficiency; updated Phase 1 data for ivosidenib and Bristol-Myers Squibb’s Vidaza in newly diagnosed acute myeloid leukemia with an IDH1 mutation
• Orchard Therapeutics: Phase 1 data for OTL-203 in MPS 1
• GENMAB: Phase 1/2 data for GEN3013 in B-cell lymphoma
• Kadmon Holdings Inc KDMN 10.27%: Phase 2 data for KD025-208 in chronic graft-versus-host disease
• Aprea Therapeutics Inc APRE 7.82%: Phase 2 data for APR-246 and Bristol-Myers Squibb’s azacitidine in TP53 mutated myelodysplastic syndrome and acute myeloid leukemia; Phase 2 data for APR-246 in combination with azacitidine in myelodysplastic syndromes
• Gamida Cell Ltd GMDA 0.2%: additional Phase 1 data for NAM-NK in non-Hodgkin lymphoma and multiple myeloma
• Bristol-Myers Squibb & bluebird bio: Phase 1 data for bb21217 in multiple myeloma
• Onconova Therapeutics Inc ONTX 19.82%‘: Phase 2 data for oral rigosertib and azacitidine in first-line high-risk myelodysplastic syndromes
• Forty Seven Inc FTSV 2.12%‘: Phase 1b data for 5F9 in combination with azacitidine for acute myeloid leukemia
• ImmunoGen, Inc. IMGN 0.64%‘: updated Phase 1 data for IMGN632 in acute myeloid leukemia and blastic plasmacytoid dendritic cell neoplasm
• Calithera Biosciences Inc CALA 5.88% – Phase 2 data for telaglenastat in combination with azacitidine in myelodysplastic syndrome
• TG Therapeutics: Phase 1 data for TG-1701 in non-Hodgkin lymphoma and chronic lymphocytic leukemia
• Curis, Inc. CRIS 14.67%: updated Phase 1 data for CA-4948 in relapsed or refractory non-Hodgkin lymphoma
• ArQule, Inc. ARQL 1.63%: Phase 1 data for ARQL 531 in B-cell malignancies
• Xencor Inc XNCR 1.11%: initial Phase 1 data for XmAb1367 in chronic lymphocytic leukemia, small lymphocytic lymphoma
• MacroGenics Inc MGNX 4.59%: updated Phase 1 data for flotetuzumab in acute myeloid leukemia/myelodysplastic syndrome
• Constellation Pharmaceuticals Inc CNST 2.46%: additional Phase 2 data for CPI-0610 and Incyte Corporation INCY 0.52%‘s ruxolitinib in myelofibrosis
• Regeneron Pharmaceuticals Inc REGN 1.06%: updated Phase 1 data for REGN1979 in follicular lymphoma
• Stemline Therapeutics Inc STML 5.15%: Phase 1/2 data for SL-401 in myelofibrosis
• CTI BioPharma Corp CTIC 2.9%: Phase 2 dose-finding study of Pacritinib in myelofibrosis
• Geron Corporation GERN 0.66%: Phase 2/3 data for imetelstat in myelodysplastic syndromes
• Precision BioSciences Inc DTIL 6.21%: Interim Phase 1/2 data for PBCAR0191 in relapsed or refractory B-cell precursor acute lymphoblastic leukemia and R/R non-hodgkin lymphoma

Tuesday

Amgen, Inc. AMGN 0.15% & GENMAB: Phase 3 data for krypolis in multiple myeloma (late-breaker abstract)

Sanofi SA SNY 0.11%: Phase 3 data for sutimlimab in cardinal cold agglutinin disease

Bristol-Myers Squibb: Phase 3 data for oral azacitidine for acute myeloid leukemia maintenance

SABCS Presentations

MacroGenics and Zai Lab Ltd ZLAB 0.29% – oral presentation of detailed results from the second interim overall survival analysis form the SOPHIA study of margetuximab in patients with HER2-positive metastatic breast cancer who have been previously treated with anti-HER2-targeted therapies (date not confirmed)

Seattle Genetics – already-released Phase 2 data for Tucatinib ONT-380 in combination with Roche Holdings AG Basel ADR Common Stock RHHBY 0.36%‘s Herceptin and oral chemotherapy Xeloda in HER2+ metastatic breast cancer (Wednesday)

G1 Therapeutics Inc GTHX 11.49% – additional Phase 1b data for Lerociclib plus AstraZeneca plc AZN 0.1%‘s Faslodex in ER+ breast cancer (Wednesday)

OncoSec Medical Inc ONCS 1.36%: interim Phase 2 data for tavo in combination with Keytruda in triple-negative breast cancer (Thursday)

Oncternal Therapeutics Inc ONCT 2.27%: Phase 1 data for cirmtuzumab, in combination with Bristol-Myers Squibb’s Abraxane (Thursday)

Athenex Inc ATNX 7.97%: Phase 3 data for oraxol in metastatic breast cancer (Friday)

ESMO-IO Presentations

Gritstone Oncology Inc GRTS 7.96% – initial safety data from the Phase 1 study of GRANITE-001 in solid tumors (date not confirmed) as well as initial safety data from the Phase 1 data for SLATE-001 in solid tumors

BIOLINERX LTD/S ADR BLRX 13.24% – Phase 2a data for BL-8040 in combination with Merck’s Keytruda in pancreatic cancer (Friday)

Earnings

Twist Bioscience Corp TWST 6% (Wednesday, after the market close)
Veru Inc VERU 2.02% (Thursday, before the market open)
Applied DNA Sciences Inc APDN 3.14% (Thursday, after the market close)

https://www.benzinga.com/general/biotech/19/12/14947992/the-week-ahead-in-biotech-ash-presentations-pick-up-steam-correvio-awaits-adcom-ruling

Epizyme’s tazemetostat shows positive action in mid-stage lymphoma study

Results from an open-label Phase 2 clinical trial evaluating Epizyme’s (NASDAQ:EPZM) tazemetostat in follicular lymphoma (FL) patients, with or without EZH2 activating mutations, showed a treatment benefit. The data were presented at ASH in Orlando.

The objective response rate (ORR) in patients with an EZH2 mutation was 69% (n=31/45) as determined by an Independent Review Committee. The ORR in patients with wild-type (naturally occurring) EZH2 was 35% (n=19/54). Complete response rates were 13% (n=6/45) and 4% (n=2/54), respectively.

The rates of stable cancer were 29% (n=13/45) and 33% (n=18/54) implying disease control rates of 98% (n=44/45) and 69% (n=37/54), respectively.

Median progression-free survival was 13.8 months and 11.1 months, respectively, and median duration of response was 10.9 months and 13.9 months, respectively.

On the safety front, the most frequent serious/life-threatening treatment-related adverse events were thrombocytopenia (3%), anemia (2%), asthenia (physical weakness/lack of energy) (1%) and fatigue (1%). The discontinuation rate was 8% and the rate of dose-limiting toxicity was 9%.

Small molecule tazemetostat inhibits an enzyme called enhancer of zeste homolog 2 (EZH2), the overexpression of which is associated with many forms of cancer since it dampens genes that play key roles in suppressing tumor development.

The company plans to file a U.S. marketing application this month seeking accelerated approval for FL. Its application for epithelioid sarcoma is currently under FDA review with an Ad Com meeting scheduled for Wednesday, December 18, ahead of the agency’s January 23, 2020 action date.

#ASH19

https://seekingalpha.com/news/3524624-epizymes-tazemetostat-shows-positive-action-in-mid-stage-fl-study

XBiotech out-licenses anti-inflammatory antibody to Janssen for up to $1.35B

XBiotech (NASDAQ:XBIT) inks an agreement with Johnson & Johnson (NYSE:JNJ) unit Janssen Biotech for global rights to anti-inflammatory candidate bermekimab.

Under the terms of the deal, XBIT will receive $750M upfront and up to $600M in milestones. It will also generate additional revenue over the next two years via a manufacturing supply and clinical services agreement with Janssen.

XBIT will use the proceeds to fund the advancement of its next generation True Human anti-IL-1⍺ antibody program, additional pipeline candidates and potential stock buybacks.

Bermekimab is a monoclonal antibody that binds to (inhibits) the pro-inflammatory protein interleukin-1alpha (IL-1α).

https://seekingalpha.com/news/3524623-xbiotech-out-licenses-anti-inflammatory-antibody-to-janssen-for-up-to-1_35b