Pipeline News and Updates
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Regulatory Update
The FDA approved tafasitamab-cxix (Monjuvi, Morphosys & Incyte), on 7/31/2020. Tafasitamab-cxix was approved in combination with lenalidomide for second-line treatment of relapsed/refractory diffuse large B-cell lymphoma. The FDA accepted the BLA for Ridgeback Biotherapeutics’ ansuvimab for the treatment of Ebola virus infections. The FDA has granted Marinus Pharmaceuticals’ ganaxolone a Rare Pediatric Disease Designation for the treatment of CDKL5 deficiency disorder, a rare refractory form of pediatric epilepsy. BMS resubmitted a BLA for idecabtagene vicleucel for the treatment of relapsed and refractory multiple myeloma. CHMP (European new drug review committee) recommended approval of Geron/Janssen’s imetelstat for the treatment of myelodysplastic syndromes. Announced Research Updates Orion announced that in the 12-week, 496 patient, Phase III REFALS trial, treatment with levosimendan did not improve the slow vital capacity in the supine position compared to placebo in patients with ALS. Levosimendan also did not improve patient functionality and survival at 48 weeks. Allergan announced that in the 12-week, 910 patient, Phase III, ADVANCE trial, monthly migraine days were reduced by 3.69 days with atogepant 10 mg, 3.86 days with 30 mg, and 4.2 days with 60 mg compared to a 2.48 days decrease with placebo in patients with four to 14 migraine days per month. In a 6-week, 477 patient, Phase III trial, viloxazine decreased the ADHD-RS-5 total score by 16.6 points with 100 mg and 17.7 points with 200 mg compared to a 10.6 point decrease with placebo in children 6 to 11 years of age with attention deficit hyperactivity disorder. Published Research Updates In a 492 patient, Phase III trial, adding pegvorhyaluronidase alfa to nab-paclitaxel plus gemcitabine resulted in overall survival of 11.2 months compared to 11.5 months with nab-paclitaxel plus gemcitabine alone in patients with hyaluronan-high metastatic pancreatic ductal adenocarcinoma. In a 195 patient Phase III trial, tivantinib did not improve progression-free survival compared to placebo in Japanese patients with highly expressed c-Met hepatocellular carcinoma with prior treatment with sorafenib. In a 12-week, 387 patient, Phase III, JADE MONO-1 trial, 24% of patients treated with abrocitinib 100 mg and 44% treated with 200 mg achieved an IGA score of clear or almost clear skin, had a 2 point or > improvement in their IGA score compared to 8% with placebo in patients with moderate to severe atopic dermatitis. A 75% or greater improvement in the Eczema Area and Severity Index (EASI-75) score was achieved by 40% of patients in the 100 mg group and by 63% in the 200 mg group compared to 12% with placebo. In a 150 day, 1,453 patient, Phase II trial, 2.6% of patients treated with nirsevimab developed medically attended RSV-associated lower respiratory tract infection compared to 9.5% with placebo in healthy infants who had been born preterm (29 weeks 0 days to 34 weeks 6 days of gestation). In a 6-week, 51 Japanese patient, Phase II trial, hemoglobin increased by 0.43 g/dL with vadadustat 150 mg, 1.13 g/dL with 300 mg, and 1.62 g/dL with 600 mg compared to a 0.47 g/dL decrease with placebo in patients with nondialysis-dependent CKD (NDD-CKD) induced anemia. In a 6-week, 60 Japanese patient, Phase II trial, hemoglobin decreased by 0.28 g/dL with vadadustat 150 mg, but increased by 0.08 g/dL with 300 mg, and 0.41 g/dL with 600 mg compared to a 1.48 g/dL decrease with placebo in patients with dialysis-dependent CKD (DD-CKD) induced anemia. By week 16, 91% of NDD-CKD patients and 71% of DD-CKD patients had achieved hemoglobin levels between 10.0 and 12.0 g/dL in both trials. GSK announced topline results from a 52-week, 271 patient, Phase III trial, where oral daprodustat was non-inferior to darbepoetin in raising mean hemoglobin levels (10.9 g/dl vs 10.8 g/dl) during weeks 40 to 52 in dialysis-dependent Japanese patients with anemia associated with chronic kidney disease. In the 40-week, 76 patient, Phase II, STAIRWAY trial, best-corrected visual acuity was improved by 9.3 letters with faricimab every 12 weeks and by 12.5 letters with every 16 weeks dosing compared to an 11.4 letter improvement with ranibizumab every 4 weeks in patients with neovascular age-related macular degeneration. Right to Try Update
The FDA has proposed requirements for the annual report for any investigational drug provided to eligible patients under the Right to Try Act. The FDA is accepting comments on the proposed rule until 9/22/2020. Regulatory Update The FDA approved brexucabtagene autoleucel (Tecartus, Gilead Sciences), on 7/24/2020, for the treatment of relapsed or refractory mantle cell lymphoma. Brexucabtagene autoleucel was approved with a boxed warning and REMS program due to the risks of CRS and neurologic toxicities. Brexucabtagene autoleucel is a one-time treatment and Gilead has priced the drug at $373,000, the same price as its other CAR-T cell therapy axicabtagene ciloleucel (Yescarta). The FDA approved abametapir (Xeglyze, Dr. Reddy's Laboratories), on 7/24/2020, for the treatment of head lice. The FDA designated MyoKardia’s mavacamten a Breakthrough Therapy for the treatment of symptomatic, obstructive hypertrophic cardiomyopathy. The FDA accepted the NDA for Aurinia Pharmaceuticals’ voclosporin for the treatment of lupus nephritis and set a PDUFA date of 1/22/2021. CHMP (European new drug review committee) recommended approval of GlaxoSmithKline’s belantamab mafodotin for the treatment of relapsed/refractory multiple myeloma, filgotinib for the treatment of rheumatoid arthritis, and bupivacaine/meloxicam for the treatment of postoperative pain. Announced Research Updates Genfit is discontinuing development of elafibranor for NASH resolution without worsening fibrosis. The company will focus the drug’s development efforts on primary biliary cholangitis. Roche discontinued development of the investigational autism treatment, balovaptan, in July 2020. UCB announced that in the 16-week, 743 patient, Phase IIIB, BE RADIANT trial, treatment with bimekizumab was superior to secukinumab in moderate-to-severe chronic plaque psoriasis patients achieving PASI 100. Published Research Updates In the 237 patient, Phase III RECOVER trial, 20.3% of patients treated with eflapegrastim developed severe neutropenia compared to 23.5% with pegfilgrastim during the first cycle of docetaxel/cyclophosphamide treatment of breast cancer. Regulatory Update
The FDA rejected leronlimab and requested additional analysis of existing data. An FDA review of clinical data for belantamab mafodotin revealed safety concerns due to 71% of patients developing keratopathy, with 44% of patients experiencing severe symptoms. However, the FDA Oncologic Drugs Advisory Committee voted 12-0 to recommend approval with a REMS program to educate patients and physicians about the risk. An FDA review of terlipressin questioned whether clinical data on hepatorenal syndrome type 1 reversal demonstrated decreased mortality, dialysis or intensive care days. However, the FDA Cardiovascular and Renal Drugs Advisory Committee voted 8-7 to recommend approval. The FDA accepted the NDA for vericiguat for reducing the risk of cardiovascular death and heart failure hospitalization following a worsening heart failure event in patients with symptomatic chronic heart failure with reduced ejection fraction, in combination with other heart failure therapies. and set a PDUFA date of 1/20/2021. The FDA accepted the NDA for the treatment of spasticity in multiple sclerosis patients and set a PDUFA date for 12/29/2020. The FDA designated mosunetuzumab a Breakthrough Therapy for the treatment of relapsed or refractory follicular lymphoma who have received at least two prior systemic therapies. Roche licensed pralsetinib from Blueprint Medicines for $675 million. Announced Research Updates Spark announced 2 to 3.3 year interim results from 12 patients enrolled in a Phase I/II trial, where SPK-8011 reduced the annual bleeding rate by 91% and infusions of FVIII by 96% in patients with Hemophilia A. Aprea announced that in a 52 patient, Phase II trial, treatment with APR-246 and azacitidine resulted in an overall response rate of 76% in patients with TP53-mutant myelodysplastic syndrome or acute myeloid leukemia. Lilly announced that in the 52-week, 1,465 patient, Phase III, OASIS-2 trial, 83.1 to 83.3% of patients treated with mirikizumab achieved a Static Physician's Global Assessment (sPGA) of 0 or 1 with at least a 2-point improvement from baseline compared to 68.5% with secukinumab in patients with moderate to severe plaque psoriasis. In the same trial, 81.4 to 82.4% of mirikizumab patients achieved a 90% or > improvement in Psoriasis Area and Severity Index (PASI 90) compared to 69.4% with secukinumab. Amplyx announced that in a 20 patient, Phase II trial, 80% of patients treated with fosmanogepix achieved clearance of Candida from blood cultures with no additional antifungal treatment, and survival at the end of study treatment, in patients with candidemia. Published Research Updates In a 3-month, 8 patient, Phase III, open-label trial, treatment with setmelanotide resulted in a 5.5% decrease in weight in patients with Bardet-Biedl syndrome. Seven of the patients completed a 9-month extension and achieved a 16.3% weight loss at 12 total months. In a 4-week, 152 patient, Phase II trial, patients treated with tradipitant had a 1.2 decrease in their patient reported nausea score compared to a 0.7 decrease with placebo in patients with idiopathic and diabetic gastroparesis. Patients who were experiencing nausea and vomiting at enrollment achieved a 1.4 point decrease. Regulatory Update
The FDA approved the oral combination of decitabine and cedazuridine (Inqovi, Astex Pharmaceuticals), on 7/7/2020, for treatment of myelodysplastic syndrome or chronic myelomonocytic leukemia. The EU approved J&J’s Ad26.ZEBOV (Zabdeno) and MVA-BN-Filo (Mvabea), a two dose vaccine regimen for the prevention of Ebola virus infection. The FDA designated Concert Pharmaceuticals’ CTP-543 a Breakthrough Therapy for the treatment of moderate-to-severe alopecia areata. The FDA accepted the BLA for AstraZeneca/Leo Pharma’s tralokinumab for treatment of moderate-to-severe atopic dermatitis. Biogen filed a BLA for aducanumab for the treatment of Alzheimer’s Disease. ChemoCentryx submitted an NDA for avacopan for the treatment of patients with ANCA-associated vasculitis. Announced Research Updates Idorsia announced that in a 3-month, 924 patient, Phase III trial, treatment with daridorexant 25 mg improved sleep maintenance and total sleep time compared to placebo in patients with insomnia. The 25 mg dose did not improve sleep onset and daytime functioning compared to placebo and the 10 mg dose did not improve any of the four measures. Bayer announced that in the 48-month, 5,734 patient, Phase III, FIDELIO-DKD trial, patients treated with finerenone had a lower incidence of kidney failure and renal death compare to placebo in patients with chronic kidney disease and type 2 diabetes. Kidney failure was defined as a sustained decrease of estimated glomerular filtration rate (eGFR) greater than or equal to 40 percent from baseline over a period of at least four weeks. Atox Bio announced that in the 28-day, Phase III, ACCUTE trial, involving 290 patients with severe necrotizing soft tissue infection, treatment with reltecimod did not improve a composite of morbidity, no more than three debridements, no further amputations, and resolution of organ dysfunction compared to placebo (48.6% vs 39.9%) in a modified Intent-to-Treat responder analysis (primary endpoint), but demonstrated a benefit in a per protocol analysis (54.3% vs 40.3%) after 17 patients were excluded. Published Research Updates In a 15-month, 891 patient, Phase III trial, treatment with hydromethylthionine did not improve the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) or the Alzheimer's Disease Co-operative Study-Activities of Daily Living Inventory (ADCS-ADL) scores compared to placebo in patients with mild to moderate Alzheimer's disease. Most patients were receiving acetylcholinesterase inhibitors, memantine or both. A separate sub-group analysis of hydromethylthionine monotherapy suggested a benefit on cognitive scores. In a 16-week, 143 patient, Phase III trial, treatment with topical agents plus nemolizumab decreased the pruritus VAS score by 42.8% compared to a 21.4% decrease with only topical agents in Japanese patients with atopic dermatitis and moderate-to-severe pruritus and an inadequate response to topical agents. In a 12-month, 50 patient, open-label, Phase II trial, treatment with axalimogene resulted in overall survival of 38% in patients with persistent or recurrent metastatic carcinoma of the cervix. In a 95 patient, Phase II trial, treatment with margetuximab plus pembrolizumab resulted in an overall response rate of 18.48% in patients with metastatic HER2-positive gastroesophageal adenocarcinoma previously treated with trastuzumab and chemotherapy. In the 48-week, 374 patient, Phase II ARPEGGIO trial, treatment with laquinimod did not differ from placebo in the percentage brain volume change compared to placebo in primary progressive MS patients. Regulatory Update
The FDA approved triheptanoin (Dojolvi, Ultragenyx) on 6/30/2020 as a source of calories and fatty acids for the treatment of pediatric and adult patients with molecularly confirmed long-chain fatty acid oxidation disorders (LC-FAOD). Ultragenyx set WAC for triheptanoin at $4,875 per 500 ml vial, which indicates an average annual cost of $138,000. The FDA has approved remimazolam (Byfavo, Acacia) on 7/2/2020 for the induction and maintenance of procedural sedation in adults undergoing surgical procedures lasting 30 minutes or less. The FDA approved fostemsavir (Rukobia, ViiV Healthcare), on 7/3/2020, in combination with other antiretrovirals, for the of treatment heavily treated adults with multidrug-resistant HIV-1 infection failing their current antiretroviral regimen due to resistance, intolerance, or safety considerations. The FDA rejected Heron Therapeutics Bupivacaine, Meloxicam (HTX-011) for a second time and requested additional data regarding exposure of excipients in preclinical reproductive toxicology studies and a process change for the allowable level of an impurity during manufacturing. Mezzion submitted an NDA for udenafil to improve the physiology of patients 12 years of age and older with single ventricle heart disease (SVHD) who have undergone a Fontan operation. The FDA designated Nodic Nanovector Lutetium (177lu) lilotomab satetraxetan, a Fast Track therapy for treatment of adults with relapsed or refractory marginal zone lymphoma who received at least two prior systemic therapies. Announced Research Updates Iterum Therapeutics announced that in the 1,670 patient, Phase III SURE 1 trial, oral sulopenem/probenecid for five days did not meet non-inferiority for test of cure compared to oral ciprofloxacin for three days (66.8% vs 78.6%) in the treatment of uncomplicated urinary tract infections in patients infected with quinolone-susceptible bacteria. However, in patients infected with quinolone-resistant organisms, sulopenem/probenecid was superior to ciprofloxacin at the test of cure visit (62.6% vs 36%). Hua announced that in a 24-week, 766 patient, Phase III trial, dorzagliatin added to metformin lowered HbA1c 0.66% compared to metformin monotherapy (a decrease of 1.02% vs 0.36%) in Chinese patients with type 2 diabetes. Helsinn and MEI Pharma discontinued a Phase III trial evaluating pracinostat in combination with azacitidine in the treatment of acute myeloid leukemia patients who are unfit to receive standard intensive chemotherapy, when a futility analysis revealed little chance of treatment success. ObsEva announced that in the 24-week, 526 patient, Phase III PRIMROSE 2 trial, heavy menstrual bleeding was reduced to 80/ml or less with the reduction being at least 50% from baseline in 75.5% of patients treated with linzagolix 200 mg and hormone add-back therapy and 56.4% with linzagolix 100 mg monotherapy compared to placebo in patients with uterine fibroids and heavy menstrual bleeding. Published Research Updates An analysis of post-marketing data from Japan found that 12.6% of 6,451 patients that took tofogliflozin experienced an ADR, with the most commonly reported events being hypoglycemia, polyuria/pollakiuria, volume depletion-related disorders, urinary tract infections, genital infections and skin diseases. In a 52-week, 62 patient, Phase III trial, treatment with weekly somapacitan was similar to daily growth hormone in the reduction of visceral, subcutaneous and total adipose tissue in Japanese adults with growth hormone deficiency Remdesivir – Update on Pricing and availability
Additional information became available on Monday, 29 June, 2020, so we have provided an update regarding pricing and availability. The FDA approved an emergency use authorization (EUA) for remdesivir to treat hospitalized patients with severe COVID-19. HHS signed an Agreement with Gilead for 500,000 treatment courses of remdesivir on 6/29/2020. This represents 100% of July production, 90% of August production and 90% of September production. The U.S. The Department of Health and Human Services will control distribution through AmerisourceBergen and hospitals will pay no more than WAC for the drug. The government will tell AmerisourceBergen how many vials can be shipped to a state. The department of health in each state will direct the wholesaler to deliver doses to the hospitals with the highest number of inpatient COVID-19 cases. The initial supply from the Federal Stockpile of 5 million doses were exhausted at the end of June 2020. HHS will stop managing distribution of remdesivir at the end of September, when supplies are expected to stabilize. Gilead has set AWP for remdesivir (Veklury) at $520 per vial or $3,120 for five days of treatment. This is the price for private insurance patients in the U.S. The U.S. government price for Medicaid and military hospitals is $390 per vial or $2,340 for a five-day course of treatment. This is also the price for developed countries. Pricing for remdesivir is more aligned with estimates from ICER that take into account the potential effect of dexamethasone. Gilead has entered into agreements with generic manufacturers to make the drug available at a substantially lower cost to developing countries, where healthcare resources, infrastructure and economics are lower. Regulatory Update The FDA rejected the BLA for abicipar pegol in June 2020 due to an unfavorable benefit-risk ratio in the treatment of neovascular (wet) age-related macular degeneration. CSL Behring licensed worldwide marketing rights for hemophilia B gene therapy etranacogene dezaparvovec from uniQure. Sarepta submitted an NDA for casimersen for the treatment of Duchenne muscular dystrophy with genetic mutations that are amenable to skipping exon 45 of the Duchenne gene. Ascendis submitted a BLA for lonapegsomatropin for the treatment for pediatric growth hormone deficiency. The FDA granted seviprotimut-L a Fast Track designation as an adjuvantive treatment of stage IIB/IIC melanoma patients, post-resection to improve recurrence-free survival. Announced Research Updates Orphazyme announced that in the 6-month, 37 patient, Phase II, dose-ranging, ORARIGAU-01 trial, treatment with arimoclomol 100mg, 200mg, or 400mg did not reduce serum chitotriosidase activity compared to placebo in patients with Gaucher disease. Acceleron announced that in the 24-week, 106 patient, Phase II, PULSAR trial, treatment with sotatercept reduced pulmonary vascular resistance by 20.5% with 0.3 mg/kg (n = 32) and 33.9% with 0.7 mg/kg (n=42) compared to a 2.1% reduction with placebo in patients with pulmonary arterial hypertension. Rhythm Pharmaceuticals announced 12-week interim results from 75 patients enrolled in a Phase II trial, where a weekly setmelanotide formulation achieved similar weight loss to a daily formulation in healthy obese patients. Published Research Updates In the 87 patient, Phase II MAJA trial, maintenance therapy with vinflunine plus best supportive care resulted in a mortality rate of 59.1% compared to 74.4% mortality with only best supportive care in parents with advanced urothelial carcinoma. In the 527 patient, Phase III FALUCA trial, treatment with fruquintinib did not improve overall survival compared to placebo (8.9 months vs 10.4 months) in patients with locally advanced/metastatic nonsquamous non-small-cell lung cancer. Regulatory Update
The FDA approved lurbinectedin (Zepzelca, Jazz Pharma/PharmaMar) on 6/16/2020 for the treatment of metastatic small cell lung cancer that has progressed during or after treatment with platinum-based chemotherapy. The FDA rejected Nabriva Therapeutics/Zavante Therapeutics’ injectable fosfomycin a second time in June 2020 due to the same manufacturing deficiencies found in 2019. The FDA has accepted the NDA for Myovant’s relugolix for the treatment of advanced prostate cancer, and set a PDUFA date of 12/20/2020. The FDA designated Insmed’s brensocatib as a Breakthrough Therapy for the treatment of non-cystic fibrosis bronchiectasis. TG Therapeutics submitted an NDA for umbralisib for the treatment of marginal zone lymphoma and follicular lymphoma. The FDA requested additional information on the efficacy analysis for Clovis Oncology’s rociletinib. The FDA has granted Ovid Therapeutics’ gaboxadol a Rare Pediatric Disease designation for the treatment of Angelman syndrome. The FDA has designated Chi-Med/Lilly’s fruquintinib Fast Track status for the treatment of patients with metastatic colorectal cancer. Announced Research Updates Brickell announced that in a 42-day, 281 patient, Phase III trial, 53.9% of patients treated with sofpironium improved their Hyperhidrosis Disease Severity Scale to two or less and had a 50% or more reduction in gravimetric sweat production compared to 36.4% that received placebo in Japanese patients with axillary hyperhidrosis. Global Data announced that a pooled analysis of six Phase II trials found that two months after midomafetamine treatment, 56% of patients did not meet PTSS diagnostic criteria and after 12 months, 67% did not qualify for a PTSD diagnosis. BeyondSpring announced interim data from 120 patients enrolled in the Phase III PROTECTIVE 2 trial, where treatment with plinabulin plus pegfilgrastim reduced grade 4 or severe neutropenia, compared to pegfilgrastim monotherapy, in patients with breast cancer treated with docetaxel, doxorubicin, and cyclophosphamide. Hua Medicine announced that in a 24-week, 463 patient, Phase III SEED trial, treatment with dorzagliatin 0.75 mg reduced HbA1c 1.15% compared to a 0.58% decrease with placebo, in Chinese patients with type 2 diabetes. In a 28-week, open-label extension of the SEED trial, patients treated with dorzagliatin continued on the drug and maintained a 1.11% HbA1c reduction, while patients switched from placebo achieved a 1.27% reduction. Roche announced that in the 1,101 patient, Phase II, IPATential150 trial, ipatasertib, added to abiraterone and prednisone or prednisolone, improved radiographic progression-free survival compared to abiraterone plus prednisone/prednisolone in patients with metastatic castration-resistant prostate cancer (mCRPC) with PTEN loss, but not in all mCRPC patients regardless of PTEN status. Provention Bio announced extended follow-up data showing that the time to develop type 1 diabetes after treatment with teplizumab increased to five years compared to two years with placebo. Sanofi announced that in a 2.4 year, 34-patient follow-up to a Phase II trial, treatment with fitusiran lowered the annualized bleed rates to 0.84 in the non-inhibitor subgroup and to 0.44 in the inhibitor subgroup. Published Research Updates In the 12-week, 155 patient, Phase IIb ASTEROID 2 trial, 62.9% of patients treated with vilaprisan had a complete absence of bleeding or spotting compared to 55.4% with ulipristal and none with placebo in patients with uterine fibroids and heavy menstrual bleeding. In an 8-week, 9 patient, open-label pilot study, treatment with ganaxolone decreased the Montgomery-Asberg Depression Rating Scale [MADRS] score from 24.4 to 12.8, and 44% achieved remission (MADRS < 10) in postmenopausal women with persistent depression despite adequate antidepressant therapy. Regulatory Update
The FDA approved inebilizumab-cdon (Uplizna, Viela Bio) on 6/11/2020 for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive. The FDA designated Insmed’s brensocatib a Breakthrough Therapy for the treatment of non-cystic fibrosis bronchiectasis. Leo Pharma announced the EU accepted the MAA for AstraZeneca/Leo Pharma’s tralokinumab as a treatment for moderate-to-severe atopic dermatitis. Announced Research Updates AbbVie announced that in the 12-week, 612 patient, Phase III, SELECT-CHOICE trial, patients treated with upadacitinib had a 2.52 reduction in their DAS28CRP score compared to a 2 point reduction with abatacept in patients with rheumatoid arthritis previously treated with a biologic. GSK announced interim data from 18 patients enrolled in the Phase I/II, open-label, DREAMM-6 trial, where treatment with belantamab mafodotin plus bortezomib and dexamethasone resulted in an overall response rate of 78% in patients with relapsed/refractory multiple myeloma. Pfizer announced that in a 12-week, 387 patient, Phase III, JADE MONO-TEEN trial, more patients treated with abrocitinib 200 mg achieved an IGA score of clear or almost clear skin and had a 2 point or > improvement in their IGA score compared to placebo in patients 12 to < 18 years of age with moderate to severe atopic dermatitis (AD) who were also on background topical therapy. Treatment with the 200 mg dose also resulted in more patients achieving at least a 75% or greater improvement in their Eczema Area and Severity Index (EASI) score compared to placebo. The 100 mg dose did not differ from placebo for IGA or EASI scores. Opthea announced that in a 12-week, 155 patient Phase IIa trial, treatment with OPT-302 plus aflibercept did not improve the number of patients that achieved a 5 letter or > gain in Best Corrected Visual Acuity compared to aflibercept monotherapy (52% vs 60%) in patients with persistent diabetic macula edema despite regular intravitreal administration of prior anti-VEGF-A monotherapy. Bluebird announced 6-month interim results for 16 patients enrolled in the Phase I/II, HGB-206 trial, where treatment with beta beglogene darolentivec resulted in total hemoglobin from 9.6 to 16.2 g/dL, HbAT87Q levels from 2.7 to 9.4 g/dL and a 99.5% mean reduction in annualized rate of vaso-occlusive crises and acute chest syndrome in patients with sickle cell disease. ADC announced that in the 145 patient, Phase II, open-label, LOTIS 2 trial, treatment with loncastuximab tesirine resulted in an ORR of 48.3% and a complete response rate (CRR) of 24.1% in patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL). ADC announced interim results from 18 patients enrolled in the Phase I/II, open-label, LOTIS 3 trial, where treatment with loncastuximab tesirine plus ibrutinib resulted in an ORR of 66.7% and a CRR of 33% in patients with relapsed or refractory DLBCL or mantle cell lymphoma (MCL). Published Research Updates In the 12-month, 81 patient, Phase II, open-label, L-MIND trial, treatment with tafasitamab plus lenalidomide resulted in an overall response rate of 60% in patients with diffuse large B cell lymphoma. In a 92 patient, Phase II, open-label trial, treatment with tafasitamab resulted in an overall response rate of 26% in diffuse large B cell lymphoma patients, 29% in follicular lymphoma patients and 27% in indolent non-Hodgkin's lymphoma patients. Regulatory Update
The FDA placed a hold on the AAVance trial, due to abnormalities in MRI imaging. Since the trial is fully enrolled and LYS-SAF302 is a single treatment, gene therapy for Sanfilippo syndrome, Lysogene stated the forecast completion in January 2022 is not expected to be delayed. The FDA designated MacroGenics’ margetuximab an Orphan Drug for the treatment of gastric and gastroesophageal junction cancer. Announced Research Updates Tenax announced that in the 6-week, 37 patient, Phase II, HELP trial, levosimendan did not reduce pulmonary capillary wedge pressure (PCWP) during exercise compared to placebo, but did reduce PCWP at rest in patients with pulmonary hypertension and heart failure with preserved ejection fraction. Gilead and Galapagos announced that in the 52-week, 1,759 patient, Phase III, FINCH 1 trial, the percentage of patients that achieved ACR20/50/70 with filgotinib 200 mg was 78%/62%/44%, filgotinib 100 mg was 76%/59%/38%, compared to adalimumab with 74%/59%/39% in patients with moderate-to-severe rheumatoid arthritis with an inadequate response to MTX. Gilead and Galapagos announced that in the 52-week, 975 patient, Phase III, FINCH 3 trial, the percentage of patients that achieved ACR20/50/70 with filgotinib 200 mg/MTX was 75%/62.3%/47.8%, filgotinib 100 mg/MTX was 73.4%/59.4%/40.1%, compared to filgotinib 200 mg monotherapy with 74.8%/61.4%/45.2%, and methotrexate monotherapy was 61.8%/48.3%/29.8% in patients with moderate-to-severe rheumatoid arthritis naive to methotrexate. Alnylam announced that in the 6-month, 39 patient, Phase III, ILLUMINATE-A trial, treatment with lumasiran decreased 24-hour urinary oxalate excretion by 53.5% compared to placebo in patients with primary hyperoxaluria type 1. Sarepta announced 1-year interim results from 3 patients enrolled in a Phase I/IIa, open-label trial, treatment with a low dose of SRP-9003 improved the North Star Assessment for Dysferlinopathy (NSAD), time to rise, four-stair climb, 100-m walk test and 10-meter walk test in patients with limb-girdle muscular dystrophy. In the same trial, 3 patients that received a high dose of SRP-9003 demonstrated a higher mean expression of transduced beta-SG in the muscle sarcolemma at 60-days compared to that seen with the lower dose. Published Research Updates In a 12-week, 391 patient, Phase III, JADE MONO-2 trial, an Investigator Global Assessment (IGA) response of clear [0] or almost clear [1], with improvement of 2 or more grades, was achieved by 38.1% of patients treated with abrocitinib 200 mg and 28.4% of those treated with 100 mg compared to 9.1% with placebo in patients with moderate to severe atopic dermatitis. A 75% improvement in the Eczema Area and Severity Index score (EASI-75) was achieved in 61% of patients treated with abrocitinib 200 mg and 44.5% of those treated with 100 mg compared to 10.4% with placebo. In a 24-week, 303 patient, Phase III trial, roxadustat, given orally three times per week, was non-inferior to darbepoetin, injected once per week, in maintaining hemoglobin between 10 to 12 g/dL (95.2% vs 91.3%) in Japanese hemodialysis patients. In a 27 patient, Phase II, open-label trial, treatment with camrelizumab added to gemcitabine, vinorelbine and pegylated liposomal doxorubicin followed by camrelizumab maintenance resulted in an overall response in 74% of patients with relapsed or refractory primary mediastinal B-cell lymphoma. Regulatory Update
Chi-Med plans to initiate a rolling NDA at the end of 2020 for surufatinib as a treatment of advanced neuroendocrine tumors. CHMP recommended that the EMA approve Ad26.ZEBOV and MVA-BN-Filo to prevent Ebola virus infection. The J&J Ebola vaccine is a two injection series. Zabdeno (Ad26.ZEBOV) is given first and followed two months later by Mvabea (MVA-BN-Filo). Announced Research Updates BioMarin announced that in a 4-year, 15 patient, Phase I/II, open-label extension trial, treatment with valoctocogene roxaparvovec resulted in a cumulative annualized bleeding rate of < 1, but Factor VIII levels declined while remaining in a range to provide hemostatic efficacy. Valoctocogene roxaparvovec is undergoing a priority review of its BLA due to being designated a Breakthrough Therapy. The drug has a PDUFA date of 8/21/2020. Immutep announced interim data from the 109-patient, Phase II, open-label TACTI-002 trial evaluating eftilagimod alpha plus pembrolizumab in the treatment of patients with non-small cell lung cancer (NSCLC) or head and neck squamous cell carcinoma (HNSCC). The data suggested an overall response rate (ORR) of 53% in 17 NSCLC patients and 39% in 18 patients with HNSCC. Iterum Therapeutics announced that in the 1,395 patient, Phase III SURE 2 trial, IV sulopenem followed by oral sulopenem/probenecid did not meet non-inferiority compared to IV ertapenem followed by oral ciprofloxacin/metronidazole or amoxicillin-clavulanate in the treatment of complicated urinary tract infections. Aveo announced that in the 38-month, 350 patient, Phase III, TIVO-3 trial, of patients treated with tivozanib, progression-free survival (PFS) was not significantly different from sorafenib (16.4 vs 19.2 months) in patients with highly refractory advanced or metastatic renal cell carcinoma that had failed at least two prior therapies, including a vascular EGFR TKI. (Note: results after 19-months have been published and suggested a PFS of 5.6 months with tivozanib compared to 3.9 months with sorafenib. Blueprint announced results from the 116 patient, Phase I/II, open label, ARROW trial. In the RET fusion–positive non-small cell lung cancer cohort, treatment with pralsetinib resulted in a 73% objective response rate (ORR) in treatment-naïve patients and 61% in patients that were previously treated with platinum-based chemotherapy. In the cohort of patients with RET-mutant medullary thyroid cancer, treatment-naïve patients had an ORR of 74% and previously treated patients had an ORR of 60%. The FDA accepted the NDA for pralsetinib for the treatment of RET fusion–positive non-small cell lung cancer and set a PDUFA date of 11/23/2020. Published Research Updates In the 1-year, 291 patient, Phase II, HER2CLIMB trial, treatment with tucatinib in combination with trastuzumab and capecitabine resulted in time to intracranial progression or death (CNS-PFS) of 9.9 months and overall survival of 18.1 months compared to 4.2 months CNS-PFS and 12 months OS with trastuzumab and capecitabine alone in patients with HER2-positive breast cancer with brain metastases. In the 48-week, 217 patient, Phase IIb BE ABLE 2 trial (a long-term follow-up to the Phase IIb BE ABLE 1 trial), 80 to 100% of bimekizumab responders maintained PASI90, 69-83% maintained PASI100 and 78-100% had an Investigator’s Global Assessment of 0/1. In the 406 patient, Phase III ADVANCE study, 16% of patients treated with eflapegrastim developed severe neutropenia compared to 24% with pegfilgrastim in patients with early-stage breast cancer. In the 55 patient, Phase II, open-label, INSIGHT trial, treatment with tepotinib did not improve progression free survival compared to standard platinum doublet chemotherapy (4.9 vs 4.4 months) in patients with epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) with MET overexpression (immunohistochemistry [IHC]2+ or IHC3+) or MET amplification having acquired resistance to EGFR inhibition. However the trial was terminated early due to poor recruitment, so all analyses are considered to be exploratory. |
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