Pipeline News and Updates
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Regulatory Update
The FDA approved loncastuximab tesirine (Zynlonta, ADC Therapeutics), on 4/21/2021, for the treatment of relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy. The FDA approved dostarlimab (Jemperli, GlaxoSmithKline), on 4/22/2021, for the treatment of recurrent or advanced endometrial cancer with deficient mismatch repair. WAC for dostarlimab has been set at $10,000 per 500 mg vial for an estimated monthly cost of $15,000. Agenus submitted a BLA for balstilimab for the treatment of recurrent/metastatic cervical cancer. The FDA lifted the hold on uniQure’s hemophilia B gene therapy, etranacogene dezaparvovec, clinical trials after extensive tissue analysis found it unlikely the gene therapy vector contributed to the development of hepatocellular carcinoma. Announced Research Updates Sunovion announced that in a six-week, 39 patient, Phase II trial, treatment with SEP-363856 did not differ from placebo in the decrease of the Scale for Assessment of Positive Symptoms–Parkinson’s Disease (SAPS-PD), with a nonsignificant decrease (2.5 points vs 1.4 point decrease), in patients with Parkinson’s psychosis. Coherus BioSciences and Junshi Biosciences announced interim results from the 514 patient, Phase III JUPITER-06 trial, where treatment with toripalimab in combination with paclitaxel/cisplatin achieved the progression free survival (PFS) and overall survival (OS) primary endpoints in patients with advanced esophageal squamous cell carcinoma. LEO Pharma announced 56-week results from 513 patients participating in the 268-week, Phase III ECZTEND trial, a long term extension of patients with moderate-to-severe atopic dermatitis that completed the ECZTRA 1 to 8 trials, where continued treatment with tralokinumab resulted in 49.7% achieving IGA 0/1 and 82.8% achieved EASI-75. Sanofi announced that in a 24-week, Phase II trial, treatment with rilzabrutinib reduced the severity of lesions and corticosteroid use in patients with pemphigus vulgaris. BMS announced that in the 16-week, 666 patient, Phase III, POETYK PSO-1 trial, 58.7% of patients treated with deucravacitinib achieved PASI 75 and 53.6% achieved a Physician's Global Assessment (sPGA) score of 0 to 1 compared to 35.1% and 32.1% with apremilast and 12.7% and 7.2% with placebo in patients with moderate to severe psoriasis. BMS announced that in the 16-week, 1,020 patient, Phase III, POETYK PSO-2 trial, 53.6% of patients treated with deucravacitinib achieved PASI 75 and 50.3% achieved an sPGA score of 0 to 1 compared to 40.2% and 34.3% with apremilast and 9.4% and 8.6% with placebo in patients with moderate to severe psoriasis. Sanofi announced that in the 150 day, 1,500 patient, Phase III, MEDLEY trial, treatment with nirsevimab reduced the development of RSV-associated lower respiratory tract infection compared to placebo in healthy late preterm and term infants of 35 weeks or greater gestational age. Published Research Updates In a 54 patient, open-label, dose-ranging, Phase IIa trial, the overall response rate was 65% with belumosudil 200 mg once daily, 69% with 200 mg twice daily and 62% with 400 mg once daily in patients with chronic graft-versus-host disease. In the 52-week, 20 patient, open-label, Phase II, ASCEND-Peds trial, treatment with olipudase resulted in a 40% improvement in splenomegaly and hepatomegaly, 32.9% improvement in predicted DLco, 0.56 point improvement in Z-scores and normalization of lipid profiles and liver transaminase in pediatric patients with acid sphingomyelinase deficiency. In the 59 patient, Phase II, PASSION trial, 47 patients received treatment daily with camrelizumab plus apatinib, which resulted in an objective response rate of 34% in patients with small cell lung cancer. In the 16-week, 743 patient, Phase IIIB, BE RADIANT trial, 61.7% of patients treated with bimekizumab achieved 100% reduction from baseline in their PASI score compared to 48.9% that received secukinumab in patients with moderate-to-severe chronic plaque psoriasis. In the 16-week, 478 patient, Phase III, BE SURE trial, 86.2% of patients treated with bimekizumab achieved PASI 90 and 85.3% achieved an IGA score of clear or almost clear compared to 47.2% and 57.2% with adalimumab in patients with moderate-to-severe chronic plaque psoriasis. Regulatory Update
The FDA approved estetrol in combination with drospirenone (Nextstellis, Mayne Pharma), on 4/16/2021 for the prevention of pregnancy. The FDA has granted TTP399 Breakthrough Therapy status as an adjunctive therapy to insulin for the treatment of type 1 diabetes The FDA designated CYNK-001 an Orphan Drug for the treatment of malignant gliomas. Amylyx plans to initiate a Phase III, ALS trial for AMX0035 in 3Q21 to satisfy an FDA request for an additional trial before an NDA could be accepted. The FDA granted FibroGen’s pamrevlumab a Rare Pediatric Disease Designation for the treatment of Duchenne muscular dystrophy (DMD). Ovid discontinued development of gaboxadol (OV101), in April 2021, for the treatment of Angelman and Fragile X syndrome, due to a lack of efficacy in both diseases. Announced Research Updates BeiGene announced interim data from 805 patients enrolled in the Phase III, RATIONALE 303 trial, where overall survival in patients treated with tislelizumab was 17.2 months compared to 11.9 months with docetaxel in patients with locally advanced or metastatic non-small cell lung cancer who had progressed on prior platinum-based chemotherapy. In patients with high PD-L1 expression, overall survival was 19.1 months with tislelizumab compared to 11.9 months with docetaxel. Lilly announced that in 61 MCL patients from the Phase I, BRUIN trial, treatment with pirtobrutinib resulted in an overall response of 52%. Immunic announced that in the 59 patient, cohort 2 of the 24-week, Phase II, EMPHASIS trial, compared to placebo, treatment with vidofludimus 10mg resulted in a 40% decrease in MRI detected lesions in the brain and spinal cord. TG Therapeutics announced that in the 96-week, 673 patient, Phase III ULTIMATE I trial, treatment with an intravenous infusion of ublituximab every six months resulted in a 60% relative reduction in the annualized relapse rate compared to daily oral teriflunomide in patients with relapsing forms of multiple sclerosis. And in the 96-week, 660 patient, Phase III ULTIMATE II trial, treatment with an intravenous infusion of ublituximab every six months resulted in a 49% relative reduction in the annualized relapse rate compared to daily oral teriflunomide in patients with relapsing forms of multiple sclerosis. Published Research Updates In the 1-year, 501 patient, Phase III, HELIOS trial, treatment with ASP0113 did not reduce a composite endpoint of all-cause mortality and adjudicated CMV end-organ disease compared to placebo in CMV seropositive subjects who underwent hematopoietic stem cell transplantation. In a 6-week, 59 patient, Phase II trial, treatment with psilocybin did not improve the 16-item Quick Inventory of Depressive Symptomatology–Self-Report (QIDS-SR-16) compared to escitalopram in patients with long-standing, moderate-to-severe major depressive disorder. While psilocybin demonstrated a benefit in secondary outcomes, the analyses of these endpoints lacked correction for multiple comparisons In the 4-week, 152 patient, open-label Phase II, MIROP trial, switching patients from pregabalin to mirogabalin reduced the visual analog scale by 15.7 mm in Japanese patients with peripheral neuropathic pain. In a 36-week, 31 patient, open-label extension of a Phase II trial, treatment with resmetirom had an 11.1% reduction in MRI-PDFF in NASH patients with persistently mild to markedly elevated liver enzymes at the end of the primary study. An 18-month, 854 patient, Phase II trial, found that at 12 months there was a 64% probability that treatment with lecanemab would result in a 25% or more reduction in the decline of the Alzheimer's Disease Composite Score (ADCOMS) compared to placebo, which missed the 80% threshold for the primary outcome. At 18 months biweekly lecanemab decreased brain amyloid and showed a reduction in the ADCOMS compared to placebo. Regulatory Update
The FDA extended the review period for Pfizer’s abrocitinib by three months and moved the PDUFA date to the end of July. The FDA granted eftilagimod alpha a Fast Track designation for the treatment of recurrent or metastatic head and neck squamous cell carcinoma. Announced Research Updates Fibrogen announced that safety data for roxadustat had inadvertently been miscalculated using post-hoc stratification factors. When the calculations were done using the pre-specified stratification factors approved by the FDA, the hazard ratios for MACE (all-cause mortality, stroke, and myocardial infarction), MACE+ (hospitalization due to heart failure and unstable angina added to MACE) and all-cause mortality were slightly higher for dialysis and non-dialysis patients. The FDA requested additional information from Provention Bio regarding how the pharmacokinetic and pharmacodynamic (PK/PD) properties compare between templizumab manufactured by Lilly and AGC Biologics. Prevention Bio has used teplizumab manufactured by Lilly for its clinical trials. The company plans to have AGC Biologics manufacturer the drug for commercial use. The FDA did not find a PK/PD bridging study to support AGC Biologics manufactured templizumab to be comparable to the Lilly manufactured drug, so additional data would be required. While Prevention Bio believes this requirement will lead to a delay in approval of templizumab, there has not been a change in the PDUFA date or advisory committee meeting. Published Research Updates ICER estimated the cost of treatment with ciltacabtagene autoleucel as $317,000 to be cost effective at $100,000 per quality adjusted life year (QALY) and $427,000 to be cost effective at $150,000 per QALY. ICER found the clinical evidence to support at least a small or substantial health benefit with a high likelihood of at least a net health benefit. The 748 patient, Phase III, MERU trial was terminated after an interim analysis did not find a survival benefit with rovalpituzumab as first-line maintenance therapy after platinum-based chemotherapy compared to placebo in patients with extensive-stage small cell lung cancer (SCLC) compared to placebo. In the 26-week, 24 patient, Phase III, open-label CARDINAL trial, 13/24 (54.2%) patients treated with sutimlimab achieved an increase in hemoglobin of at least 2 g/dL or an average hemoglobin level of at least 12 g/dL and did not require a transfusion or pharmacotherapy between weeks 5 to 26 in patients with cold agglutinin disease. In a 91 patient, Chinese, Phase II study anlotinib demonstrated an average progression free survival of 20.7 months compared to 11.1 months in patients with relapsed medullary thyroid carcinoma. In the 6-week, 37 patient, Phase II, HELP trial, levosimendan did not reduce pulmonary capillary wedge pressure (PCWP) during exercise compared to placebo in patients with pulmonary hypertension and heart failure with preserved ejection fraction. Regulatory Update
The FDA approved viloxazine (Qelbree, Supernus Pharmaceuticals), on 4/2/2021, for the treatment of attention-deficit hyperactivity disorder in patients 6 to 17. Three members of the FDA Peripheral and Central Nervous System Drugs Advisory Committee, which reviewed and rejected aducanumab, published an editorial in JAMA to explain why the drug should not be approved. The authors felt that post hoc analysis should not discredit the negative study, since no other trial based on reduction of beta-amyloid has shown a benefit. They also questioned whether the FDA worked too closely with the study sponsor in a reanalysis of the trials. In conclusion, the authors did not feel that a single positive study justified the approval of aducanumab. Mezzion re-submitted an NDA for udenafil as a treatment to improve exercise capacity in patients with single ventricle heart disease who have undergone a Fontan operation. AbbVie announced that the FDA accepted the NDA for atogepant as prophylaxis of episodic migraine. AbbVie expects a PDUFA date in late 3Q21. Akebia submitted an NDA for vadadustat for the treatment of anemia due to chronic kidney disease in both dialysis dependent and non-dependent patients. Amryt submitted an NDA for oleogel-S10 for the treatment of the cutaneous manifestations of Junctional and Dystrophic Epidermolysis Bullosa. BeyondSpring submitted an NDA for plinabulin plus granulocyte colony-stimulating factor for the prevention of chemotherapy-induced neutropenia. Johnson & Johnson and Legend Biotech have completed a rolling NDA for ciltacabtagene autoleucel as a treatment for relapsed and/or refractory multiple myeloma. CTI BioPharma has submitted an NDA for pacritinib for the treatment of patients with myelofibrosis with severe thrombocytopenia. Announced Research Updates Revance announced that in a 36-week, 301 patient, Phase III trial, daxibotulinumtoxinA improved the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) at six-weeks by 12.7 points with 125 units and 10.9 points with 250 units compared to a 4.3 point improvement with placebo in patients with moderate to severe cervical dystonia. There was no statistical difference between doses in the TWSTRS score. The median duration of effect (loss of 80% of improvement) with 250 units. Published Research Updates In the 24-week, 106 patient, Phase II, PULSAR trial, treatment with sotatercept reduced pulmonary vascular resistance more than placebo by 145.8 dyn·sec·cm(−5) with 0.3 mg/kg and 239.5 dyn·sec·cm(−5) with 0.7 mg/kg in patients with pulmonary arterial hypertension. In a 355 patient, open-label, Phase III, Chinese trial, progression-free survival (PFS) was 7.6 months with tislelizumab added to paclitaxel and carboplatin and 7.6 months with tislelizumab plus nab-paclitaxel and carboplatin compared to 5.5 months with paclitaxel and carboplatin alone in patients with squamous non-small cell lung cancer. In the three-month, 114 patient, Phase III COMPASS trial, patients treated with volanesorsen had a 71.2% decrease in triglycerides compared to a 0.9% decrease with placebo in patients with multifactorial severe hypertriglyceridaemia or familial chylomicronaemia syndrome, who had a BMI of 45 kg/m2 or less and fasting plasma triglyceride of 500 mg/dL or higher. In a seven-day, 34 patient, cross-over, Phase II trial, 52% of patients treated with velusetrag achieved at least a 20% reduction in the gastric emptying half-time compared to 5% with placebo in patients with diabetic or idiopathic gastroparesis. |
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