Pipeline News and Updates
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Regulatory Update
The FDA accepted a resubmitted BLA for Bluebird Bio’s and Bristol-Myers Squibb’s idecabtagene vicleucel for the treatment of multiple myeloma and set a PDUFA date for 3/27/2021. The FDA accepted the BLA and the EMA accepted the MAA for UCB’s bimekizumab for the treatment of moderate to severe plaque psoriasis. ADC Therapeutics submitted a BLA for loncastuximab tesirine for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The EMA approved Galapagos’ and Gilead’s filgotinib to treat moderate to severe active rheumatoid arthritis. Announced Research Updates Sarepta announced 24-month interim results from four patients in a Phase I/II trial, where microdystrophin gene therapy (SRP-9001) improved their North Star Ambulatory Assessment (NSAA) compared to baseline in four ambulatory Duchenne muscular dystrophy participants between the ages of 4 and 7. SRP-9001 increased micro-dystrophin protein levels at 12-weeks, but Sarepta has not reported levels since that time. Agenus announced that in a 143 patient, Phase II trial, treatment with balstilimab and zalifrelimab resulted in a 22% objective response rate (ORR) in patients with advanced cervical cancer. Agenus announced that in a 160 patient, Phase II trial, treatment with balstilimab resulted in a 14% ORR in patients with advanced cervical cancer. Published Research Updates In a 6-week, 45 patient, Phase II trial, reproxalap ophthalmic solution was non-inferior to prednisone acetate ophthalmic solution with or without reproxalap ophthalmic solution in reducing anterior chamber inflammatory cell count in noninfectious uveitis patients. During the first 12-months of a 24-month extension of the Phase II trial, 23 patients continued to improve velocity to stand from supine, to run/walk 10 meters and to climb 4 stairs after 18 total months of treatment. When the outcomes in 46 vamorolone-treated DMD patients were compared to a group of 68 patients in the CINRG Duchenne Natural History Study (corticosteroid-naive, n = 19; corticosteroid-treated, n = 68) over a similar 18-month period, there was no difference in time to stand, but an improvement in the time to run/walk 10 meters and to climb 4 stairs. In a 55 patient, Phase II trial, plinabulin was non-inferior to pegfilgrastim in reducing neutropenia in patients receiving docetaxel chemotherapy. In the 1,032 patient, Phase III, open-label, DANUBE trial, neither durvalumab plus tremelimumab or durvalumab monotherapy improved overall survival compared to standard-of-care chemotherapy in patients with metastatic urothelial carcinoma. Regulatory Update
The FDA accepted the NDA for Orphazyme’s arimoclomol for the treatment of Niemann-Pick disease Type C and set a PDUFA date for 3/17/2021. The FDA accepted the NDA for ChemoCentryx’s avacopan for the treatment of ANCA-associated vasculitis and set a PDUFA date for 7/7/2021. The FDA granted Gilead’s magrolimab a Breakthrough Therapy designation for the treatment of myelodysplastic syndrome. The FDA designated MedImmune’s mavrilimumab an Orphan Drug for the treatment of giant cell arteritis. Apellis submitted an NDA and MAA for pegcetacoplan for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). Agenus began a rolling BLA for balstilimab for the treatment of recurrent/metastatic cervical cancer. Announced Research Updates Myovant announced that in a 28-week, 477 patient, open-label, long-term extension trial for LIBERTY 1 and 2, 87.7% of patients treated with relugolix, estradiol and norethindrone acetate achieved a menstrual blood loss volume of less than 80 mL and an 89.9% reduction in menstrual blood loss. Marinus announced that in the 10-week, 101 patient, Phase III, Marigold trial, treatment with ganaxolone resulted in a 32.2% reduction in 28-day major motor seizure frequency compared to a 4% decrease with placebo in children and young adults with CDKL5 deficiency disorder (CDD). Marinus plans to submit an NDA for ganaxolone for the treatment of CDD in mid-2021 and an MAA by the end of 3Q21. BeiGene announced results from the 334 patient, open-label, Phase III, Chinese RATIONALE 304 trial, where treatment with tislelizumab added to standard chemotherapy (pemetrexed plus carboplatin or cisplatin) resulted in progression-free survival (PFS) of 9.7 months compared to a PFS of 7.6 months in patients treated with standard chemotherapy alone in patients with non-squamous non-small cell lung cancer. Mirati announced interim results from 30 patients enrolled in a 330 patient, Phase II, open-label trial, where treatment with sitravatinib and nivolumab resulted in a 37% objective response rate in patients with advanced or metastatic urothelial carcinoma. Clementia and Ipsen announced interim data after 18-months from 97 patients enrolled in the 48-month, 110 patient, Phase III, MOVE trial, where treatment with palovarotene reduced heterotopic ossification volume by 62% compared to a natural history group of patients with fibrodysplasia ossificans progressiva (FOP). Published Research Updates In a 12-week, 483 patient, Phase II, dose-ranging trial, treatment with relugolix reduced pelvic pain 6.2 points with 10 mg, 8.1 points with 20 mg and 10.4 points with 40 mg compared to a 10.6 point decrease with leuprorelin and 3.8 point decrease with placebo in patients with pain associated with endometriosis. In a 12-week, 315 patient Phase II/III trial, adults treated with dasotraline 4-8 mg decreased binge days by one day compared to placebo in adults ages 18–55 years with moderate to severe binge eating disorder. In a 24-week, 242 patient, Phase II trial, patients treated with oligomannate had a decrease in their ADAS-Cog12 Score of 1.39 points with 600 mg and 2.58 points with 900 mg compared to 1.45 points with placebo in Chinese patients with mild to moderate Alzheimer’s disease. In a 66 patient, Phase II, open label, dose ranging trial, treatment with rozanolixizumab improved platelet count to 50x109/L or > in all dosing groups in patients with primary immune thrombocytopenia (ITP). In a 164 patient, Phase I trial, Ad26.ZEBOV and MVA-BN-Filo vaccines were well tolerated and elicited strong, durable humoral and cellular immune responses for the Ebola virus in healthy patients. The 172 patient, Phase III, open-label, SANET-p trial was stopped early when an interim analysis found that treatment with surufatinib resulted in progression-free survival (PFS) of 10.9 months compared to 3.7 months with placebo in Chinese patients with progressive, advanced pancreatic neuroendocrine tumors. The 198 patient, Phase III, open-label, SANET-ep trial was stopped early when an interim analysis found that treatment with surufatinib resulted in PFS of 9.2 months compared to 3.8 months with placebo in Chinese patients with with unresectable or metastatic, well differentiated, extrapancreatic neuroendocrine tumor. In the 129 patient, Phase I/II, CodeBreak 100 trial, treatment with sotorasib resulted in progression-free survival of 6.3 months in patients with non–small-cell lung cancer and four months in colorectal cancer in patients with advanced solid tumors harboring the KRAS p.G12C mutation. In an extension of a Phase II induction trial, 15% of induction non-responders that received mirikizumab 600 mg and 43.8% of non-responders that received mirikizumab 1000 mg achieved clinical remission after an additional 12-weeks of treatment (24-weeks total). Among initial non-responders 26.3% that achieved clinical remission maintained it at 52-weeks. Regulatory Update
An FDA review of Mallinckrodt’s terlipressin questioned whether clinical data on hepatorenal syndrome type 1 reversal, as demonstrated by a decrease in serum creatinine, demonstrated decreased mortality, need for dialysis or intensive care days. However, the FDA Cardiovascular and Renal Drugs Advisory Committee voted 8-7 to recommend approval in July 2020. The FDA was not convinced and rejected the NDA for terlipressin and requested data to support a positive risk-benefit profile for terlipressin for HRS-1 patients in September 2020. The FDA granted BeyondSpring’s plinabulin a Breakthrough Therapy Designation for the prevention of chemotherapy-induced neutropenia. The FDA requested that Sarepta use a different potency assay when manufacturing its microdystrophin gene therapy, before using the drug in a Phase III trial. The EMA requested 52-week data for 134 patients enrolled in a Phase III trial of BioMarin’s valoctocogene roxaparvovec for the treatment of Hemophilia A. Announced Research Updates Merck announced that gefapixant 45 mg BID reduced the 24-hour coughs per hour average 18.45% more than placebo in the 12-week, 730 patient, Phase III, COUGH-1 trial and by 14.64% more than placebo in the 24-week, 1,314 patient, Phase III, COUGH-2 trial in patients with refractory or unexplained chronic cough. Treatment with gefapixant 15 mg BID did not differ from placebo in neither the COUGH-1 nor COUGH-2 trials. Taste-related adverse effects were frequent with the 45 mg dose with an incidence of 58% in COUGH-1 and 68.6% in COUGH-2. Corbus announced that in the 52-week, 365 patient, Phase III, RESOLVE-1 trial, treatment with lenabasum did not improve the American College of Rheumatology Combined Response Index for Systemic Sclerosis (ACR CRISS) scores compared to placebo in patients with diffuse cutaneous systemic sclerosis. Gilead and Galapagos announced that in the 156-week, 739 patient, Phase II, DARWIN 3 trial (extension trial for Darwin I and II), there was an increase in infections with filgotinib, but no other safety issues. Published Research Updates In a 52-week, 121 patient, Phase III trial, treatment with vosoritide increased annualized growth velocity by 1.57 cm/year more than placebo in children (ages 5 to 18) with achondroplasia. In the 24-week, 256 patient, Phase II, WILLOW trial, treatment with brensocatib resulted in the time to the first exacerbation of 134 days with 10 mg and 96 days with 25 mg compared to 67 days with placebo in patients with non-cystic fibrosis bronchiectasis In the 266 patient, Phase III FRESCO trial, the most common adverse events with fruquintinib were hypertension, palmar-plantar erythrodysesthesia syndrome and proteinuria. In the 679 patient, Phase III TARGET trial, 91.3% of patients treated with ceftobiprole achieved a 20% or more reduction from baseline in lesion size at 48 to 72 hours compared to 88.1% of patients treated with vancomycin plus aztreonam in patients with acute bacterial skin and skin structure infection. Regulatory Update
The FDA approved a bioresorbable collagen implant that contains bupivacaine (Xaracoll, Innocoll), on 8/31/2020, for acute postsurgical pain relief following open inguinal hernia repair. The FDA approved somapacitan (Sogroya, Novo Nordisk), on 9/2/2020, for adults with growth hormone deficiency. The FDA approved pralsetinib (Gavreto, Roche), on 9/4/2020, for the treatment of metastatic RET fusion–positive non–small cell lung cancer (NSCLC), as detected by an FDA-approved test. The FDA rejected Mezzion’s udenafil, in August 2020, as a treatment of single ventricle heart disease and requested additional details and documentation. The FDA accepted the NDA for CorMedix’s taurolidine as a catheter lock solution in hemodialysis patients for the prevention of catheter related blood stream infections and set a PDUFA date for 2/28/2021. The FDA accepted the NDA for Aurinia Pharmaceuticals’ voclosporin, for the treatment of lupus nephritis, and set a PDUFA date for 1/22/2021. The FDA accepted the NDA for Ascendis Pharma’s lonapegsomatropin, for the treatment of pediatric growth hormone deficiency, and set a PDUFA date for 6/25/2021. The FDA designated Mustang Bio’s MB-107 an Orphan Drug for the treatment of X-linked severe combined immunodeficiency (bubble boy disease). Announced Research Updates J&J discontinued development of pimodivir, for the treatment for influenza A infection, after an interim analysis of a Phase III trial in hospitalized patients with influenza, did not find a benefit compared to placebo. J&J also discontinued a Phase III trial evaluating pimodivir in the treatment of influenza A in non-hospitalized patients. Akebia announced that in the 36-week, 1,751 patient, Phase III, PRO2TECT Correction trial, vadadustat was non-inferior to darbepoetin in the change in hemoglobin (0.05 g/dL difference) and hemoglobin level (10.35 vs 10.39 g/dL) in CKD patients with anemia not on dialysis, who had not received previous ESA treatment. In the 36-week, 1,725 patient, Phase III, PRO2TECT Conversion trial, vadadustat was non-inferior to darbepoetin in the change in hemoglobin (0.01 g/dL difference) and hemoglobin level (10.77 vs 10.77 g/dL) in CKD patients with anemia not on dialysis, who had been receiving an ESA. The PRO2TECT Correction and Conversion trials included 3,471 CKD patients with anemia not on dialysis and found that vadadustat caused more major adverse cardiovascular events than darbepoetin (HR 1.17). Published Research Updates In the 509 patient, Phase III, BROCADE3 trial, veliparib added to carboplatin and paclitaxel improved progression-free survival at 2-years to 14.5 months compared to 12.6 months without veliparib in patients with HER2-negative advanced breast cancer and a germline BRCA1 or BRCA2 mutation. In a 12-month, 286 patient, Phase IIb, open-label, dose-ranging trial, treatment with avacincaptad pegol reduced geographic atrophy growth by 27.4% with 2 mg and 27.8% with 4 mg compared to placebo in patients with geographic atrophy secondary to dry age-related macular degeneration. In a 6-month, 105 patient, Phase II trial, treatment with vupanorsen lowered triglyceride 47% with weekly 20 mg, 36% with 40 mg every four weeks, and 53% with 80 mg every four weeks compared to a 15% decrease with placebo in patients with hypertriglyceridemia, type 2 diabetes and non-alcoholic fatty liver disease. In the 24-week, 177 patient, Phase II/III, CENTAUR trial, treatment with AMX0035 (a combination of sodium phenylbutyrate and taurursodiol) resulted in a 1.24 point decrease per month in functional status (Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised - ALSFRS-R) compared to a 1.66 month decrease with placebo. Most patients in the trial were receiving riluzole, edaravone, or both. Regulatory Update
The FDA approved clascoterone cream (Winlevi, Cassiopea), on 8/27/2020, for the treatment of acne in patients 12 years and older. Clascoterone cream is not expected to be available until early 2021. The FDA accepted the NDA for tepotinib for the treatment of metastatic non-small cell lung cancer harboring METex14 skipping alterations. The FDA notified Tricida that additional clinical data would be required to demonstrate the durability and effect of veverimer on serum bicarbonate and the applicability to patient care. NewAmsterdam Pharma (NAP) acquired the rights to develop and market obicetrapib (AMG 899) from Amgen in August 2020. NAP plans to evaluate obicetrapib in a Phase III cardiovascular outcome trial in 2021. The EU granted conditional approval for imlifidase as a desensitization treatment in highly sensitized kidney transplants patients. Announced Research Updates Novartis announced that in the 24-week, Phase III, ASCEMBL trial, treatment with asciminib produced a superior major molecular response (MMR) rate compared to bosutinib in patients with Philadelphia chromosome-positive chronic myeloid leukemia. Dermavant announced that in the 12-week, 510 patient, Phase III, PSOARING 1 trial, 35.4% of patients treated with tapinarof 1% daily resulted in achievement of the Physician Assessment (PGA) scores of clear or almost clear and at least a 2-point improvement in the PGA score in 35.4% of patients compared to 6% with placebo in patients with plaque psoriasis. Dermavant also announced that in the 12-week, 515 patient, Phase III, PSOARING 2 trial, 40.2% of patients treated with tapinarof 1% daily resulted in achievement of the Physician Assessment (PGA) scores of clear or almost clear and at least a 2-point improvement in the PGA score in 35.4% of patients compared to 6.3% with placebo in patients with plaque psoriasis. Akcea announced that in a 6-month, 114 patient, Phase II, dose-ranging trial, treatment with AKCEA-APOCIII-LRX lowered triglycerides up to 62% and apoC-III up to 74%, while increasing HDL by up to 42% in patients with hypertriglyceridemia who have established cardiovascular disease (CVD) or are at risk for CVD. Published Research Updates In an 84-day, 18 patient, Phase II trial, treatment with emixustat did not improve IL-1beta, IL-6, IL-8, TGFbeta-1, and VEGF in the aqueous humor compared to placebo in patients with proliferative diabetic retinopathy. Only 17.4% of patients completed a 52-week, 161 patient, Phase III, trial evaluating sirukumab in the treatment of giant cell arteritis. Limited data suggested that fewer patients treated with sirukumab developed a flare compared to placebo. In a 128 patient, Phase II trial, veliparib added to cisplatin and etoposide did not differ from only cisplatin and etoposide in patient reported neurotoxicity. |
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