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Regulatory Update
The FDA approved dasiglucagon (Zegalogue, Zealand Pharma), on 3/23/2021, for the treatment of severe hypoglycemia in people with diabetes aged 6 and older. Dasiglucagon will be available as an autoinjector and prefilled syringe. The FDA approved idecabtagene vicleucel (Abecma, Bristol Myers Squibb and bluebird bio), on 3/27/2021, for the treatment of adult patients with multiple myeloma who have received at least four prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody). Idecabtagene vicleucel was approved with a black box warning for cytokine release syndrome, neurotoxic events, and prolonged cytopenias as well as hemophagocytic lymphohistiocytosis/macrophage activation syndrome. The FDA’s Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee voted 19-1 against recommending approval for tanezumab, due to concerns over safety and the proposed drug safety strategy to prevent neuropathy and destructive joint disease. The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) recommended ponesimod and estetrol/drospirenone for approval. Announced Research Updates Roche licensed tominersen from Ionis. Roche suspended the Phase I, GEN-PEAK trial in 2020 due to the occurrence of two intrathecal catheter related infections, but later restarted the trial. GEN-PEAK is evaluating tominersen’s pharmacokinetic and pharmacodynamic profile. Roche discontinued dosing in the Phase III GENERATION HD1 and GEN-EXTEND trials, in March 2021, at the recommendation of the independent data monitoring committee when an interim analysis questioned the drug’s potential benefit/risk profile. The trials are evaluating tominersen as a treatment for Huntington’s disease. The GEN-PEAK trial is continuing and Roche will continue to monitor safety and efficacy in patients from the GENERATION HD1 and GEN-EXTEND trials. Novartis announced that in the 200 patient, open-label, Phase III, VISION trial, treatment with Lu-PSMA-617 improved overall survival and radiographic progression-free survival compared to standard of care in patients with progressive PSMA-positive metastatic castration-resistant prostate cancer. AZ announced that in a 109 patient, open-label, Phase II trial, treatment with cediranib plus olaparib did not improve progression-free survival compared to cediranib alone in patients with recurrent, metastatic or persistent endometrial cancer. BrainStorm announced that in a 28-week, 16 patient, open-label, Phase II trial, treatment with mesenchymal stem cells neurotrophic growth factors (MSC-NTF) resulted in 14% of patents having at least a 25% improvement in the timed 25-foot walk (T25FW) test and 13% had at least a 25% improvement in the 9-hole peg test (9-HPT) compared to none in a historical registry of patients with progressive multiple sclerosis. LSK BioPharma announced that in the 152 patient, Phase II APPROVE trial, treatment with apatinib plus pegylated liposomal doxorubicin resulted in an objective response rate of 43.1% compared to 10.9% with pegylated liposomal doxorubicin alone in patients with platinum-resistant or refractory ovarian cancer. Orphazyme announced that in a 20-week, 150 patient, Phase II/III trial, treatment with arimoclomol did not improve the body myositis functional rating scale compared to placebo in patients with inclusion body myositis. UniQure announced that an investigation by an independent lab found that it was highly unlikely that etranacogene dezaparvovec caused hepatocellular carcinoma in a patient enrolled in the HOPE-B trial. The patient had several risk factors for developing liver cancer including hepatitis C, hepatitis B, non-alcoholic fatty liver disease and history of smoking. Published Research Updates In an 8-week, 301 patient, Phase III trial, treatment with viloxazine decreased the ADHD-RS-5 total score by 17.6 points with 200 mg and 17.5 points with 400 mg compared to an 11.7 point decrease with placebo in children 6 to 11 years of age with attention deficit hyperactivity disorder. In a four-week, 69 patient, Japanese, open-label, Phase II trial, treatment with a single subcutaneous dose of nemolizumab did not reduce pruritus compared to daily oral nalfurafine hydrochloride in hemodialysis patients with uremic pruritus. In the 16-week, 838 patient, Phase III, JADE COMPARE trial, an IGA score of clear or almost clear skin, with a 2 point or > improvement in the IGA score was achieved by 48.4% of patients treated with abrocitinib 200-mg, 36.6% with 100-mg abrocitinib group and 36.5% with dupilumab compared to 14.0% with placebo in patients with moderate to severe atopic dermatitis receiving topical therapy. A 75% or greater improvement in the Eczema Area and Severity Index (EASI-75) score was achieved by 70.3% of patients treated with abrocitinib 200-mg, 58.7% with 100-mg abrocitinib group and 58.1% with dupilumab compared to 27.1% with placebo In a 24-month, 5,404 HIV-negative patient, Phase IIb/III trial, 138/2,404 patients who received five immunizations of the Sanofi Pasteur HIV vaccine with the GSK immunity-boosting adjuvant became infected with HIV compared to 133/2,700 patients that received placebo. The trial was terminated when an interim analysis determined a lack of efficacy compared to placebo. Regulatory Update
The FDA approved ponesimod (Ponvory, Johnson & Johnson), on 1/19/2021, for the treatment of relapsing forms of multiple sclerosis. The FDA accepted the NDA for Merck’s belzutifan for the treatment of von Hippel-Lindau disease-associated renal cell carcinoma, not requiring immediate surgery. A PDUFA date was set for 9/15/2021. The FDA accepted the NDA for mavacamten for the treatment of symptomatic obstructive hypertrophic cardiomyopathy and set a PDUFA date for 1/28/2022. Announced Research Updates Lilly announced that in the 12-week, 1,160 patient, Phase III, LUCENT-1 trial, more patients treated with mirikizumab 200 mg achieved remission compared to placebo in patients with moderate-to-severe active ulcerative colitis (UC). Solid Biosciences announced preliminary results from six patients at 12-24 months in the Phase I/II, IGNITE-DMD trial, where treatment with SGT-001 microdystrophin gene therapy resulted in an improvement of 1 point in the North Star Ambulatory Assessment (NSAA) score with a low dose of SGT-100 and 0.3 points with a high dose compared to a 4 point decline with placebo in children with Duchenne muscular dystrophy. In the 6-Minute Walk Test (6MWT) treatment with SGT-100 improved the distance walked by 49.7 meters with the high dose and 37 meters with the low dose compared to placebo. Forced vital capacity (% predicted FVC) at one year improved 3.9% and 16.7% with the low-dose and high-dose groups compared to a 10.7% decline with placebo. Sarepta announced two-year interim results from three patients enrolled in a Phase I/IIa, open-label trial, where that treatment with a low dose of SRP-9003 improved the North Star Assessment for Dysferlinopathy (NSAD) by 5.7 points in patients with limb-girdle muscular dystrophy. Patients also saw an improvement in time to rise, four-stair climb, 100-meter walk test and 10-meter walk test. Sarepta also announced one-year results from the same trial, where three patients received a high dose of SRP-9003 and demonstrated a four point improvement in their NSAD, time-to-rise, four-stair climb, 100-meter walk test and 10-meter walk test. Both doses of SRP-9003 increased beta-sarcoglycan protein levels in skeletal and cardiac muscle. Sage Therapeutics announced that in the 12-month 725 patient, open-label, Phase III, SHORELINE trial, a 14-day treatment with zuranolone 30 mg resulted in 489 patients responding to initial treatment. Among responders, 42.9% maintained remission at 1-year, while 25.6% required a second 14-day course of therapy, 11.9% required 3 courses, 10.8% used 4 courses, and 8.8% needed 5 courses. Repeat courses of zuranolone were given 56 days after completion of the 14-day course of treatment. Strongbridge Biopharma announced that in the 8-week, 44 patient, Phase III, LOGICS endogenous Cushing’s syndrome trial, 54.5% of patients that were stabilized on levoketoconazole, but had their therapy withdrawn, had a loss of mean urinary free cortisol response compared with to patients that remained on levoketoconazole. Published Research Updates The incidence of fractures with odanacatib over five years was examined in data from the LOFT trial and its long-term extension. The incidence of subtrochanteric, femoral shaft or hip fractures was 1.93% with odanacatib compared to 3.11% with placebo. The incidence of hip fracture only was 1.53% with odanacatib compared to 3.03% with placebo. Though rare, patients treated with odanacatib had more low-energy fractures and atypical fractures. In the 16-week, 80 patient, open-label, Phase III, PEGASUS trial, patients treated with pegcetacoplan increased their hemoglobin by 3.84 g/dL more than patients treated with eculizumab in patients with paroxysmal nocturnal hemoglobinuria with hemoglobin levels lower than 10.5 g per deciliter despite eculizumab therapy. In a 50 patient, Phase II trial, inhaled levosimendan was non-inferior to intravenous levosimendan in lowering systolic pulmonary artery pressure (PAP) in children ages one to five scheduled for cardiac surgery. In a 36-week, 818 patient, Phase III trial, patients treated with oligomannate had a decrease in their ADAS-Cog12 Score of 2.15 points less than placebo in Chinese patients with mild to moderate Alzheimer's disease. In the 16-week, 215 patient, Phase II, ECZTRA 5 trial, tralokinumab was non-inferior to placebo for positive anti-tetanus (91.9% vs 96.1%) and anti-meningococcal (86.0% vs 84.2%) responses in patients with moderate-to-severe atopic dermatitis. Regulatory Update
The FDA approved tivozanib (Fotivda, AVEO Oncology), on 3/10/2021, for the treatment of relapsed or refractory renal cell carcinoma following two or more prior lines of therapy. The FDA accepted the NDA for Cara Therapeutics’ and Vifor Pharma’s difelikefalin for the treatment of moderate-to-severe pruritus in hemodialysis patients and set a PDUFA date for 8/23/2021. The FDA extended the PDUFA date for belumosudil by three months to allow additional time to review new data submitted by Kadmon. The new PDUFA date is 8/30/2021. The FDA designated Steba Biotech’s padeliporfin, an Orphan Drug, for the treatment of upper tract urothelial cancer. Announced Research Updates Gilead announced that patients who completed the 14-day blinded portion of the CAPELLA trial were enrolled in an open-label extension where they received lenacapavir subcutaneously every six months and an optimized background regimen. After 26 weeks, 73% (19/26) achieved an undetectable viral load (< 50 copies/mL). Published Research Updates In a 34 patient, Phase II, open-label trial, treatment with adavosertib resulted in an objective response rate of 29.4% in patients with recurrent uterine serous carcinoma. Regulatory Update
The FDA approved the combination of serdexmethylphenidate plus methylphenidate (Azstarys, KemPharm), on 3/2/2021 for the treatment of attention deficit hyperactivity disorder (ADHD) in patients age six years and older. The FDA accepted the BLA for efgartigimod for the treatment of generalized myasthenia gravis and set a PDUFA date for 12/17/2021. Strongbridge submitted an NDA for levoketoconazole, for the treatment of endogenous Cushing’s syndrome. Reata submitted an NDA for bardoxolone methyl for the treatment of chronic kidney disease caused by Alport syndrome. Shanghai Junshi Biosciences initiated a rolling BLA for toripalimab for the treatment of patients with recurrent or metastatic nasopharyngeal carcinoma. Announced Research Updates BrainStorm announced that in a 28-week, 189 patient, Phase III trial, treatment with MSC-NTF did not improve the number of patients that achieved at least a 1.25 point improvement per month in their Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score compared to placebo in patients with amyotrophic lateral sclerosis (ALS). In the trial 34.7% of MSC-NTF patients had a non-significant improvement in their ALSFRS-R score compared to 27.7% with placebo. The FDA calculated a slightly different non-significant difference between the two groups (32.6% vs 27.9%). The FDA also found a modest excess in mortality in patients treated with MSC-NTF. Inovio announced that in the 36-week, 201 patient, Phase III REVEAL 1 trial, treatment with VGX-3100 did not result in a significant reduction in histopathological regression of high-grade squamous intraepithelial lesions (HSIL) compared to placebo (22.5 vs 11.1%) in patients with HPV-16/18-associated cervical HSIL. However, there was a significant difference in the 193 patient modified intention to treat group (23.7 vs 11.3%). Lilly announced that in the 40-week, 1,879 patient, Phase III, SURPASS-2 trial, treatment with subcutaneous tirzepatide reduced HbA1c and weight by 2.09% and 7.8 Kg with 5 mg, 2.37% and 10.3 kg with 10 mg and 2.46% and 12.4 kg with 15 mg compared to a 1.86% and 6.2 kg reduction with subcutaneous semaglutide in patients with type 2 diabetes receiving metformin. Galapagos announced interim results after 13 weeks from 240 patients enrolled in the Phase III MANTA and MANTA-RAy safety trials, where a similar number of men had a 50% or greater decline in sperm concentration with filgotinib (8.3%) or placebo (6.7%). Pfizer announced that in a 12-week, 285 patient, Phase III, JADE TEEN trial, an IGA score of clear or almost clear skin with at least a 2 point improvement in the IGA score was achieved by 46.2% of patients treated with abrocitinib 200 mg and 41.6% with 100 mg compared to 24.5% with placebo in patients 12 to 17 years of age with moderate to severe atopic dermatitis (AD) who were also on background topical therapy. EASI-75 was achieved by 72% of patients who received abrocitinib 200 mg and 68.5% with 100 mg compared to 41.5% with placebo Published Research Updates In a 43 patient, phase I/II trial, patients treated with rovalpituzumab tesirine plus nivolumab with or without ipilimumab demonstrated an overall response rate of 30% in patients with previously treated extensive-stage small cell lung cancer. In a 52-week, 323 Japanese patient, Phase III, trial, vadadustat was non-inferior to darbepoetin alfa in mean Hb at weeks 20 and 24 (10.61 g/dL vs 10.65 g/dL) in patients with hemodialysis-dependent CKD. In the 15-day, 300 patient, Phase III CONFIRM trial, 32% of patients treated with terlipressin plus albumin achieved reversal of hepatorenal syndrome (HRS) compared to 17% with albumin alone in patients with Type 1 HRS (HRS-1). In the CONFIRM trial, HRS reversal was defined as two consecutive serum creatinine measurements of 1.5 mg per deciliter or less at least 2 hours apart and survival without renal-replacement therapy for at least 10 days after the completion of treatment. A 32-month long-term extension, open-label Phase III trial, included 843 patients from three previous trials. Treatment with peficitinib resulted in ACR20/50/70 being maintained in 78.%/63.3%/44.1% of Asian patients with rheumatoid arthritis. Adverse events were experienced in 94.4% of patients. Most ADR were mild with the most common were nasopharyngitis and herpes zoster. In a 923-day long-term extension of the Phase II, diabetes prevention trial, the mean time to develop type 1 diabetes was 59.6 months in teplizumab patients compared to 27.1 months with placebo Interim results from 60 patients enrolled in the 400 patient, Phase III OVAL trial, suggested that treatment with ofranergene obadenovec plus paclitaxel demonstrated a 58% CA-125 response in patients with platinum-resistant ovarian cancer. In the 323 patient, Phase I/II, open-label, dose-ranging, BRUIN trial, 121 patients had efficacy data available for analysis. Treatment with pirtobrutinib resulted in an overall response of 62% in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma previously treated with a covalent BTK inhibitor. In the 366 patient, Phase III, FORWARD I trial, treatment with mirvetuximab soravtansine did not improve progression-free survival compared to standard chemotherapy (paclitaxel, pegylated liposomal doxorubicin, or topotecan) in patients with folate receptor alpha-positive, platinum-resistant epithelial ovarian cancer, who had received up to three prior lines of therapy. In a 51 patient, open-label, Phase II trial, treatment with camrelizumab plus decitabine resulted in progression-free survival of 20 to 21.6 months in patients with relapsed/refractory classical Hodgkin lymphoma who failed PD-1 inhibitors. Regulatory Update
The FDA approved casimersen (Amondys 45, Sarepta), on 2/25/2021, for the treatment of Duchenne muscular dystrophy in patients with a confirmed mutation amenable to exon 45 skipping. WAC to treat a 20 Kg patient is $300,000 per year. The FDA approved melflufen (Pepaxto, Oncopeptides) in combination with dexamethasone, on 2/26/2021, as a fourth line treatment for relapsed or refractory multiple myeloma. The FDA approved fosdenopterin (Nulibry, BridgeBio Pharma and Origin Bioscience) to reduce the risk of death due to Molybdenum Cofactor Deficiency Type A. The FDA accepted the NDA for gefapixant for the treatment of chronic cough and set a PDUFA date for 12/21/2021. The FDA designated tipifarnib a Breakthrough Therapy for the treatment of recurrent or metastatic HRAS mutant head and neck squamous cell carcinoma (HNSCC) with variant allele frequency of 20% or > after disease progression on platinum-based chemotherapy. The FDA designated Immunocore’s tebentafusp a Breakthrough Therapy for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma. The European Medicines Agency’s (EMA) approved retifanlimab for the treatment of locally advanced or metastatic squamous cell anal carcinoma. Announced Research Updates The FDA has put a hold on trials for bluebird bio’s gene therapy beta beglogene darolentivec due to the development of acute myeloid leukemia and myelodysplastic syndrome in two trial patients. Italfarmaco announced seven-year data from a long-term extension of a Phase II trial, where adding givinostat to corticosteroids resulted in a delay in loss of ambulation to 16 years compared to 13.4 years in a historical group that received corticosteroids only in patients with Duchenne Muscular Dystrophy. Respiratory function also declined at a slower rate. AstraZeneca announced that in the 823 patent, Phase III, KESTREL trial, adding tremelimumab to durvalumab did not improve overall survival compare to cetuximab with cisplatin or carboplatin plus 5-fluorouracil in patients with recurrent or metastatic head and neck squamous cell carcinoma with tumors that expressed high levels of PD-L1. Immunicum announced that in the 88 patient, Phase II, open-label, MERECA trial, treatment with ilixadencel plus sunitinib resulted in overall survival of 35.6 months compared to 25.3 months with sunitinib monotherapy in patients with renal cell carcinoma. Amgen and AstraZeneca announced that in the 52-week, 1,061 patient, Phase III NAVIGATOR trial, treatment with tezepelumab reduced the annualized asthma exacerbation rate by 56% compared to placebo in patients with severe asthma who were receiving medium to high-dose inhaled corticosteroids plus at least one additional controller medication with or without oral corticosteroids. Published Research Updates In the 128 patient, Phase II, dose-ranging, open-label, KarMMa trial, treatment with idecabtagene vicleucel resulted in an overall response rate of 73% in patients with resistant multiple myeloma. In a five-week, 182 patient, Phase II trial, treatment with xanomeline and trospium decreased the total Positive and Negative Syndrome Scale (PANSS) score by 11.6 points compared to placebo in patients with schizophrenia who were experiencing acute psychosis. In the 12-week, Phase I/II, Simplici-T1 trial, compared to placebo, TTP399 lowered HbA1c 0.7% in the 20 patient, Part 1 of the study and 0.21% in the 85 patient, Part 2 of the study in patients with type 1 diabetes receiving insulin. In the 126 patient, Phase III GENUINE trial, ublituximab in combination with ibrutinib had an overall response rate of 83% compared to 65% with ibrutinib alone in patients with relapsed or refractory chronic lymphocytic leukemia with at least one f 17p deletion, 11q deletion, or TP53 mutation. In the 52-week, 594 patient, Phase III, ALPS trial, treatment with roxadustat improved hemoglobin by 1.692 g/dL compared to placebo in chronic kidney disease (CKD) patients with anemia. In a 52-week, 1,043 patient, open-label, Phase III, trial, roxadustat was non-inferior to epoetin alfa in changes in hemoglobin (2.57 vs 2.36 g/dL) and hemoglobin response (88.2% vs 84.4%) in CKD patients with anemia and new to dialysis. In a 52-week, 387 Parkinson’s Disease patient extension of the Japanese COMFORT-PD trial, treatment with opicapone reduced OFF time in patients originally randomized to opicapone and those who originally received placebo but were changed to opicapone. In a 144 patient, Phase IIb trial, treatment with TLPLDC vaccine did not improve disease-free survival in the intention-to-treat analysis, but an improvement in the vaccine group was found in the per protocol analysis (62.9% vs. 34.8%) in patients with resected stage III/IV melanoma. |
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