Kite Pharma Inc. (NASDAQ:KITE) and Novartis AG (NYSE:NVS; SIX:NOVN) each provided updates on their lead chimeric antigen receptor (CAR) T cell therapies targeting CD19. Updates for both programs, which are nearing FDA review, occurred at the American Society of Hematology (ASH) meeting in San Diego.
Kite said it began submitting a rolling BLA for axicabtagene ciloleucel (KTE-C19) to treat relapsed or refractory aggressive B cell non-Hodgkin lymphoma (NHL). It hopes to complete the submission in 1Q17. The BLA is based on data from the Phase I/II ZUMA-1 study, in which the therapy led to an initial ORR of 76% in patients with refractory diffuse large B cell lymphoma (DLBCL). After three months of follow-up, the ORR fell to 39% (see BioCentury Extra, Sept. 26).
In new data announced Sunday, Kite said nine (82%) of 11 acute lymphoblastic leukemia (ALL) patients treated with axicabtagene ciloleucel in the Phase I ZUMA -3 and ZUMA-4 trials achieved complete remission, or complete remission with incomplete or partial hematological recovery. The company said one patient died of cytokine release syndrome (CRS), and another due to a fungal infection unrelated to the candidate. It said five (38%) of 13 enrolled patients experienced grade 3 or greater CRS, and five (38%) had a grade 3 or greater neurological event, with no reports of cerebral edema.
Next year, Kite expects to begin Phase II studies of axicabtagene ciloleucel to treat ALL. Kite added $2.86 to $53.62 on Monday.
On Sunday, Novartis said it plans to submit a BLA for CTL019 in early 2017 to treat pediatric relapsed or refractory B cell ALL. It intends to base the BLA on the Phase II ELIANA trial, from which it presented data Saturday, and to submit an MAA to EMA later next year.
The new data showed CTL019 produced a complete remission, or complete remission with incomplete blood count recovery, in 41 of 50 (82%) evaluable patients after three months. At six months, 60% of patients were relapse-free. The company said 48% of patients experienced grade 3 or 4 CRS, and 15% experienced grade 3 neurological or psychiatric events, including encephalopathy. There were no grade 4 neurological events.
Novartis said its BLA will also include data from the Phase II ENSIGN study. In results presented Sunday, the candidate produced an 69% ORR in 29 evaluable ALL patients after a median 6.4 months of follow-up, with eight patients experiencing relapses.
Also at ASH, researchers from the University of Pennsylvania presented results of a Phase I study of CTL119, a humanized CD19-targeted CAR T product to treat pediatric relapsed/refractory ALL. The therapy is designed to increase persistence by preventing immune-mediated rejection. Researchers said 26 (87%) of 30 patients achieved a complete response, with 23 remaining in remission after a median 4.2 months of follow-up. All 19 patients who had not received prior CTL019 therapy achieved complete remission.
Novartis has exclusive, worldwide rights from UPenn to develop and commercialize CAR immunotherapies for cancer, including CTL019, under a 2012 deal. Novartis scientists were among co-authors of the CTL119 study's abstract, and its presenter is a consultant to the pharma.
NeuroDerm Ltd. (NASDAQ:NDRM) gained $4.10 (26%) to $19.65 on Monday after revealing a new regulatory path in the U.S. for ND0612 to treat Parkinson's disease. ND0612 delivers liquid levodopa/carbidopa continuously via a subcutaneous belt pump.
The company said that based on conversations with FDA, two Phase III trials are no longer needed for a regulatory submission, and that it will instead conduct comparative pharmacokinetic trials which are to start "in the upcoming months." NeuroDerm said it will suspend the Phase III iNDiGO trial of its low-dose formulation of the therapy, ND0612L, and no longer intends to conduct a separate Phase III trial of high-dose version ND0612H.
NeuroDerm plans to add about 50 patients to the ongoing BeyoND long-term safety trial to evaluate a new ND0612 dosing regimen, which will be used in the pharmacokinetic trials. The company said it also may amend iNDiGO to be a life cycle management trial.
JHL Biotech Inc. (TPex-E:6540) granted Sanofi (Euronext:SAN: NYSE:SNY) rights in China to develop and commercialize biosimilar rituximab (JHL1101), as well as options for rights to other JHL candidates. JHL is to receive $21 million up front and is eligible for $236 million in milestones, plus royalties.
Sanofi also invested NT$2.6 billion ($79.6 million) in JHL by purchasing 28.3 million shares at NT$90 in a separate private placement.
JHL is to lead development, registration and manufacturing of JHL1101, and Sanofi will lead its commercialization in China. The partners may expand the deal into other markets.
According to a regulatory filing, the deal also includes JHL's biosimilar bevacizumab (JHL1149), biosimilar trastuzumab (JHL1188), and biosimilar adalimumab (JHL1228).
Biogen Inc. (NASDAQ:BIIB) and the Genentech Inc. unit of Roche (SIX:ROG; OTCQX:RHHBY) market Rituxan rituximab. Genentech also markets Avastin bevacizumab and Herceptin trastuzumab. AbbVie Inc. (NASDAQ:ABBV) markets Humira adalimumab.
In May, JHL opened a biomanufacturing facility in Wuhan, giving it the largest single-use cell culture capacity in Asia (see BioCentury Extra, May 10).
Agios Pharmaceuticals Inc. (NASDAQ:AGIO) slipped $7.10 (12%) to $49.87 on Monday after reporting new data from Phase I studies of AG-519 and AG-348, two small molecule activators of pyruvate kinase R to treat pyruvate kinase deficiency. After market hours, Agios reported new data from a Phase I study of AG-120 to treat hematological malignancies including acute myelogenous leukemia (AML).
In a Phase I trial of AG-519 in healthy volunteers, the company said it is investigating an ongoing case of drug-related cholestatic hepatitis. The patient received 300 mg AG-519 daily, one of several regimens ranging from 50 mg-1,250 mg in the dose-escalation trial. Agios had previously reported a case of grade 2 thrombocytopenia from the trial, driving down shares by 15% on June 9 (see BioCentury Extra, June 9).
In a separate study, Agios said AG-348 led to a hemoglobin increase of >1 g/dL from baseline in 15 (47%) of 32 evaluable patients in the Phase II DRIVE-PK study. All 15 were among the study's 26 evaluable patients with at least one missense mutation.
After market close, Agios said AG-120 led to an overall response rate (ORR) of 38% and complete remission rate of 18% among 78 evaluable patients in a dose-escalation Phase I trial. Median duration of response was 10.2 months. The study included patients with isocitrate dehydrogenase 1 (IDH1) mutant positive AML, as well as non-AML malignancies with IDH1 mutations. AG-120 is an inhibitor of mutated IDH1.
Among 63 patients with relapsed or refractory AML, AG-120 led to an ORR of 33% and complete remission rate of 16%, with a median duration of response of 6.5 months. Agios hopes to submit an NDA for the therapy in 2017.
In May, Agios regained full worldwide rights to AG-120 from Celgene Corp. (NASDAQ:CELG) (see BioCentury Extra, May 17).
Data from all three programs were presented at the American Society of Hematology (ASH) meeting in San Diego.
Novartis AG (NYSE:NVS; SIX:NOVN) and Global Blood Therapeutics Inc. (NASDAQ:GBT) each reported data from studies of treatments for sickle cell disease. Novartis' data from a study of crizanlizumab (SEG101, formerly SelG1) were the driver of its deal to acquire Selexys Pharmaceuticals Corp. last month (see BioCentury Extra, Nov. 21).
In the Phase II SUSTAIN trial, Novartis said high-dose crizanlizumab reduced the median annual rate of sickle cell-related pain crises (SCPC) vs. placebo by 45.3% (1.63 vs. 2.98, p=0.010), meeting the study's primary endpoint. A low dose did not meet the endpoint (2.01 vs. 3.0, p=0.180). Patients with a history of 2-10 pain crises in the prior 12 months were given 5.0 mg/kg or 2.5 mg/kg IV crizanlizumab every four weeks, alone or with hydroxyurea therapy, for 50 weeks.
High-dose crizanlizumab also significantly increased time to first and second SCPC. Data were presented at the American Society of Hematology (ASH) meeting in San Diego and published in the New England Journal of Medicine.
Novartis gained crizanlizumab, a humanized mAb against P selectin (SELP; CD62P), by exercising an option to acquire Selexys under a 2012 deal.
Separately, Global Blood said once-daily GBT440 given for up to six months led to a "profound and durable" reduction in hemolysis among all 41 patients in an ongoing Phase I/II study to treat sickle cell disease. Compared with placebo, GBT440 given for at least 90 days significantly increased hemoglobin and reduced irreversibly sickled cells (p=0.006 and p<0.001, respectively). Data were presented at the ASH meeting.
The allosteric modifier of hemoglobin oxygen affinity has Fast Track designation in the U.S. and Orphan Drug designation in the U.S. and EU to treat sickle cell disease. Global Blood has begun screening patients for the Phase III HOPE study of the candidate (see BioCentury Extra, Oct. 24).
GBT lost $1.85 (10%) to $17.25 on Monday.
Spark Therapeutics Inc. (NASDAQ:ONCE) and Alnylam Pharmaceuticals Inc. (NASDAQ:ALNY) released updated results from ongoing hemophilia trials at the American Society of Hematology (ASH) meeting in San Diego.
Spark gained $0.58 to $50.58 on Monday, as investors appeared relatively unperturbed by immune responses in patients receiving SPK-9001. On Saturday, the company and partner Pfizer Inc. (NYSE:PFE) reported a second immune response among nine patients receiving the gene therapy in an ongoing Phase I/II study to treat hemophilia B, about a month after reporting the first. Both are related to the therapy's adeno-associated virus (AAV) capsid (see BioCentury Extra, Nov. 3).
The companies said seven of the nine patients have "consistent and sustained" Factor IX activity levels as of a Nov. 30 data cutoff, with a mean steady-state level greater than 28% of normal. The partners have said natural history data suggest Factor IX activity levels of at least 12% of normal are sufficient to reduce the risk of joint bleeds and the need for prophylactic therapy (see BioCentury Extra, May 19).
On Monday, Spark announced a deal with Selecta Biosciences Inc. (NASDAQ:SELB) that could improve its therapies' safety by suppressing neutralizing antibodies. Spark gained exclusive rights to Selecta's Synthetic Vaccine Particles platform for co-administration with Factor XIII, with options for up to four additional genetic targets. Spark paid $10 million up front for the technology and invested $5 million in Selecta, which is eligible for $430 million in milestones, plus royalties.
SPK-9001 is an AAV that delivers the Factor IX gene to the liver. Spark said the Selecta deal does not affect the ongoing trial of SPK-9001.
Separately, Alnylam said RNAi candidate fitusiran (ALN-AT3) reduced median annualized bleeding rates to zero from a median of 31 among 16 patients in a Phase I study to treat hemophilia A and B with inhibitors, as of an Oct. 6 cutoff. In a Phase II open label extension study of fitusiran, Alnylam said 11 of 16 patients without inhibitors have experienced no spontaneous bleeds, and the median annualized bleeding rate was 1.0, compared to a pre-study rate of 4.0. Next year, Alnylam plans to begin Phase III testing of fitusiran, an RNAi therapeutic targeting anti-thrombin III (AT3; SERPINC1) mRNA.
Alnylam lost $0.33 to $41.24 on Monday.
Wilson Therapeutics AB (SSE:WTX) said Decuprate bis-choline tetrathiomolybdate (WTX101) met the primary endpoint in a Phase II study to treat Wilson's disease, in which excess copper accumulates in the body. Next year, the company expects to begin a Phase III study of the second-generation analog of ammonium tetrathiomolybdate.
Wilson said that after 24 weeks of treatment, 79% of patients in the study's intent-to-treat population achieved or maintained normal levels of free copper, or had a 25% drop in free blood copper from baseline, to meet the primary endpoint (p<0.001). It also reported a 77% mean reduction in serum free copper at week 24 compared to baseline (p<0.0001), and significant improvement in neurological status (p<0.001) and disability (p<0.001).
Wilson said Decuprate was well-tolerated, with reversible liver enzyme elevation occurring in 39% of patients. Six of the study's 28 patients discontinued the study, including three due to adverse events.
The study evaluated newly-diagnosed Wilson's disease patients who received either no prior treatment or standard of care for up to two years. The company said patients had hepatic impairment in varying degrees at the time of enrollment, and most had neurological symptoms.
Wilson gained SEK2.75 to SEK54.5 on Monday.
John Jenkins will step down as director of the Office of New Drugs (OND) at FDA's Center for Drug Evaluation and Research (CDER) on January 6, the agency announced Monday.
During his 15 years leading OND, Jenkins has been responsible for designing and managing FDA's review processes and for implementing numerous congressionally mandated innovations such as the biosimilars approval pathway, the breakthrough therapies program, and numerous expedited review initiatives.
"He and his staff, which has grown to more than 1,000, have successfully navigated many high-profile controversies related to new drugs -- while at the same time having thousands of interactions with industry and other stakeholders, and making timely decisions about INDs and NDAs," CDER Director Janet Woodcock wrote in a letter to CDER staff.
Woodcock will be OND's acting director while the agency searches for Jenkins' successor. Peter Stein, who was hired as deputy director of OND in November, is a candidate. Prior to joining FDA, Stein was VP for late-stage development in diabetes and endocrinology at the Merck Research Laboratories unit of Merck & Co. Inc. (NYSE:MRK) (see BioCentury Extra, Nov. 8).
The Senate Monday voted 85-13 to cut off debate on the 21st Century Cures Act. The procedural vote sets the stage for enactment of the legislation later this week. President Obama endorsed the bill strongly over the weekend.
The Republican chairs of U.S. Senate and House committees responsible for oversight of federal biomedical research have written a letter to President-elect Donald Trump urging him to retain Francis Collins as NIH director.
Collins is "the right person, at the right time, to continue to lead the world's premier biomedical research agency," the letter said. It was dated Dec. 2 and signed by Sen. Lamar Alexander (R-Tenn.), chair of the Health, Education, Labor and Pensions Committee; Sen. Roy Blunt (R-Mo.), chair of the Senate Appropriations subcommittee on Labor, Health and Human Services, Education and Related agencies; Rep. Fred Upton (R-Mich.), chair of the Energy & Commerce Committee; and Rep. Tom Cole (R-Okla.), chair of the House Appropriations subcommittee on Labor, Health and Human Services, Education and Related Agencies.
The letter, which cites Collins' "intellectual prowess, renowned scientific experience, and outstanding leadership skills," is an implicit criticism of Rep. Andy Harris (R-Md.), who has publicly announced his interest in being nominated as NIH director. Harris, a physician, worked as an obstetric anesthesiologist at The Johns Hopkins University for about 30 years and was a primary investigator on one NIH grant. If nominated and confirmed by the Senate, Harris would break a tradition dating to 1887 of appointing NIH directors who have had extensive experience conducting and leading scientific research.
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