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Regulatory Update
The FDA approved artesunate (Amivas LLC), on 5/26/2020, for the treatment of severe malaria in adult and pediatric patients. Until Amivas transitions artesunate's distribution through wholesalers, healthcare providers treating patients with severe malaria should call CDC to obtain IV artesunate. The CDC Malaria Hotline (770-488-7788) is available Monday–Friday, 9 am–5 pm EST. Outside these hours, providers should call 770-488-7100 and ask to speak with a CDC Malaria Branch clinician. The FDA accepted the NDA for Eiger BioPharmaceuticals/Merck’s lonafarnib for treatment of Progeria and Progeroid Laminopathies and set a PDUFA date of 11/20/20. The EMA accepted the MAA for AstraZeneca/FibroGen’s roxadustat for the treatment of anemia in adult patients with chronic kidney disease. The EMA accepted the MAA for Incyte/MorphoSys’ tafasitamab for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma. The EMA accepted the MAA for bluebird bio/Celgene/Bristol-Myers Squibb’s idecabtagene vicleucel for the treatment of adult patients with multiple myeloma who have received at least three prior therapies. Announced Research Updates Viiv announced data from an interim analysis of a 4,600 patient, Phase IIb/III, HIV prophylaxis trial, where 0.38% of patients that received long-acting, injectable cabotegravir every eight weeks developed HIV compared to 1.21% with daily oral emtricitabine/tenofovir disoproxil fumarate in men who have sex with men and transgender women who have sex with men. Kadmon announced that in the 6-month, 126 patient, Phase II, open-label, ROCKstar trial, treatment with belumosudil resulted in an overall response rate of 73% with 200 mg QD and 74% with 200 mg BID in patients with chronic graft-versus-host disease who have received at least two prior lines of systemic therapy. Gilead and Galapagos announced results from the 58-week, 1,348 patient, Phase IIb/III, SELECTION trial. During the first 10 weeks of the trial patients received filgotinib 100 mg, 200 mg or placebo. Patients treated with filgotinib 100 mg did not achieve remission more than placebo, while the 200 mg dose did provide an improvement in the number of patients achieving remission. The 558 patients that achieved remission were re-randomized to filgotinib or placebo for an additional 48 weeks. In the maintenance part of the trial, 37.2% of patients treated with filgotinib 200 mg achieved clinical remission compared to 11.2% with placebo and 23.8% treated with filgotinib 100 mg achieved clinical remission compared to 13.5% with placebo in patients with ulcerative colitis. Syndax announced that in a 608 patient, Phase III trial, entinostat plus exemestane did not improve overall survival in patients with advanced hormone receptor positive, human epidermal growth factor receptor 2 negative (HR+, HER2-) breast cancer that had progressed on a non-steroidal aromatase inhibitor. Due to the lack of efficacy in the Phase III metastatic cancer trial, Syndax will not file an NDA for that indication. Published Research Updates In a 180 patient, Phase II trial, treatment with tremelimumab plus durvalumab resulted in overall survival of 6.6 months compared to 4.1 months with best supportive care in patients with urothelial cancer (note this trial defined statistical significance as a 2-sided p < 0.10 and the achieved difference was a p = 0.7). In an 8-week, 204 patient, Phase II trial, 33.3% of patients treated with serlopitant reduced their Worst Itch Numeric Rating Scale (WI-NRS) score by at least 4 points compared to 21.1% with placebo in patients with mild to moderate psoriasis. In a 50-patient, Phase II trial, treatment with camrelizumab plus apatinib resulted in an overall response rate of 43.3% of 40 patients that received continuously dosed apatinib, but 0% in 10 patients that received intermittent apatinib in patients with triple-negative breast cancer. In a 48 patient, Phase II study, P2Y12 reaction units < 100 was achieved by 91% of patients that received a single 8 mg subcutaneous dose of selatogrel and 96% that received a 16 mg dose in patients that were experiencing an acute myocardial infarction. In the 34-patient, Phase II, open-label, EVOLVE trial, treatment with cediranib plus olaparib resulted in objective responses and PFS of 0%/55% in platinum-sensitive patients, 20%/50% in platinum-resistant patients, and 8%/39% in highly resistant disease in patients with PARP inhibitor resistance ovarian cancer. Regulatory Update
The FDA approved ripretinib (Qinlock, Deciphera Pharmaceuticals), on 5/18/2020, for the treatment of advanced gastrointestinal stromal tumors (GISTs). The FDA accepted the BLA for Sanofi’s sutimlimab for the treatment of hemolysis in adult patients with cold agglutinin disease (CAD) and set a PDUFA date for 11/13/2020. The FDA accepted the NDA for Rhythm Pharmaceuticals’ setmelanotide for the treatment of pro-opiomelanocortin deficiency obesity and leptin receptor deficiency obesity and set a PDUFA date of 11/27/2020. Sunovion discontinued development of dasotraline and withdrew the NDAs for the treatment of moderate-to-severe binge eating disorder and attention deficit hyperactivity disorder on 5/13/2020. The drug had a PDUFA date of 5/14/2020. Cytodyn completed a rolling BLA for use of leronlimab in combination therapy with HAART for treatment of HIV. Announced Research Updates MyoKardia announced that in the 30-week, 251 patient, Phase III EXPLORER-HCM trial, 37% of patients treated with mavacamten reached the composite endpoint of achievement of a 1.5 mL/kg/min or > improvement in peak VO2 accompanied by an improvement of at least a 1 NYHA functional class or achievement of a 3.0 mL/kg/min or > improvement of peak VO2 with no worsening in NYHA functional class compared to 17% reaching the endpoint with placebo in patients with NYHA Class II or III obstructive hypertrophic cardiomyopathy. Soligenix announced that in cycle 1 of the 8-week, 166 patient, Phase III FLASH trial, 16% of patients treated with 6-weeks of SGX301 had at least a 50% reduction in lesions compared to 4% with placebo in patients with early-stage cutaneous T-cell lymphoma. In the open-label, 12-week, 155 patient, cycle 2 of the FLASH trial, 40% of patients treated with 12-weeks of SGX301 had at least a 50% reductions in lesions. Genfit announced that in the 72-week, 1,070 patient, Phase III, RESOLVE-IT trial, treatment with elafibranor did not result in resolution of non-alcoholic steatohepatitis (NASH) without worsening of fibrosis compared to placebo (19.2% vs 14.7%) in patients with biopsy proven NASH with stage 2 or stage 3 fibrosis. Protalix announced that in the 12-month, Phase III, open-label, BRIDGE trial, 22 patients with Fabry disease stabilized on agalsidase alfa were switched to pegunigalsidase alfa and improved their annualized change in eGFR from ‑5.90 mL/min/1.73m2/year to -1.19 mL/min/1.73m2/year. BMS announced that 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. The FDA rejected the BLA for ide-cel in May 2020 and requested additional information on the manufacturing processes. BMS hopes to provide the new documentation and refile the BLA before the end of July. Blueprint announced that in the 116 patient, Phase I/II, open label, ARROW trial, treatment with pralsetinib resulted in a 65% ORR in patients with RET fusion-positive non-small cell lung cancer and 61% in 80 patients that were previously treated with platinum-based chemotherapy. J&J announced data after 11.5-months in the 29 patient, Phase Ib/II CARTITUDE-1 trial, where JNJ-4528 demonstrated an overall response rate of 100% and complete response of 86% in patients with relapsed multiple myeloma. Amgen announced data from 42 advanced colorectal cancer patients with a KRAS p.G12C mutation enrolled in the Phase I, open-label, dose ranging, CodeBreak 100 trial, where treatment with AMG 510 led to an overall response rate in 3/42 of all patients and 3/25 that received the highest dose (960 mg). Amgen announced data from 22 patients with 10 cancers other than non-small cell lung cancer or colorectal cancer but with a KRAS p.G12C mutation enrolled in the Phase I, open-label, dose ranging, CodeBreak 100 trial, where treatment with AMG 510 led to a partial response rate in 3/22 patients (10 patients had pancreatic cancer). Amgen plans to file a BLA for AMG 510 by the end of 2020. Helsinn and MEI Pharma announced that in a 64 patient, Phase II, open-label trial, 33% of patients treated with pracinostat 45 mg and azacitidine achieved a complete response rate in patients with high-risk myelodysplastic syndromes. AB Science SA announced that in a 36-week, 355 patient, Phase III trial, treatment with masitinib reduced the severe asthma exacerbation rate by 35% compared to placebo in patients with severe asthma uncontrolled by oral corticosteroids. Urovant announced that in a 40-week, 505 patient, blinded extension of the EMPWUR trial, patients treated with vibegron had a larger decrease in micturitions (-2.2 vs -1.7 per 24 hours), urgency (-3.4 vs -3.2 per 24 hours), and total urinary incontinence episodes (-2.5 vs -1.9 per 24 hours) compared to tolterodine. ImmunoGen announced that in the 60 patient, Phase Ib/II, open-label, FORWARD II trial, treatment with mirvetuximab soravtansine plus bevacizumab resulted in an overall response rate of 43% in patients with folate receptor alpha-positive, resistant ovarian cancer. ReGenTree announced that in the 18 neurotrophic keratopathy patient, Phase III, SEER-1 trial there was no difference between RGN-259 and placebo in corneal wounds healed, but there were more patients with complete corneal healing (6/10 vs 1/8). Published Research Updates In a 22 patient, Phase II trial, treatment with tavokinogene telseplasmid plus pembrolizumab resulted in a 41% objective response rate in patients with advanced melanoma with low frequencies of checkpoint positive cytotoxic lymphocytes. In a 56 patient, Japanese trial, prophylactic landiolol after surgery did not reduce the incidence of postoperative atrial fibrillation compared to placebo in post-esophagectomy patients. In the 448 patient, Phase III, ESCORT trial, overall survival for patients treated with camrelizumab was 8.3 months compared to 6.2 months with docetaxel or irinotecan in patients with metastatic esophageal squamous cell carcinoma. In a 6-month 90 patient, Phase II trial, followed by a 12-month, 77 patient extension, treatment with atabacestat did not improve MMSE scores, and RBANS were worse, compared to placebo in patients with early Alzheimer’s disease. In a 375 patient, Phase IIb/III trial, remimazolam was non-inferior to propofol as a sedative hypnotic for general anesthesia. Regulatory Update
The FDA approved selpercatinib (Retevmo, Lilly) on 5/8/2020, for the treatment of non-small cell lung cancer, advanced medullary thyroid cancer and advanced RET fusion-positive thyroid cancer. The FDA requires identification of a RET gene alteration must be determined before initiating treatment. Selpercatinib is taken twice a day until the disease progresses or there is unacceptable toxicity. Lilly set WAC for a 30-day supply of selpercatinib at $20,600. Selpercatinib is the first drug approved to treat cancers with mutation or fusion in the RET gene, but the drug will eventually have competition from pralsetinib, a second RET fusion mutation therapy from Blueprint Medicines. Blueprint filed an NDA for pralsetinib in 1Q2020, so a competitor for selpercatinib may be available in late 2020 or early 2021. The FDA approved capmatinib (Tabrecta, Novartis) on 5/6/2020, for the treatment of metastatic non-small cell lung cancer (NSCLC) whose tumors have a mutation that leads to mesenchymal-epithelial transition (MET) exon 14 skipping as detected by an FDA-approved test. Novartis has set WAC for a 28-day supply of capmatinib at $17,950. Capmatinib is the first drug approved to treat cancers with MET exon 14 skipping alterations. The drug will eventually have competition from tepotinib, a MET inhibitor being developed by EMD Serono. The FDA accepted the NDA for Bristol-Myers Squibb/Juno/Therapeutics Celgene’s lisocabtagene maraleucel for the treatment of large B-cell lymphoma and set a PDUFA date for August 2020. The PDUFA date was then delayed by three months in May 2020 to allow the FDA time to review new requested data for the drug. The new PDUFA date is 11/16/2020. The FDA granted Amgen/Cytokinetics’ omecamtiv mecarbil, Fast Track designation as a treatment of chronic heart failure with reduced ejection fraction (HFrEF). The EMA granted Acceleron Pharma’s sotatercept a Priority Medicines (PRIME) designation for the treatment of patients with pulmonary arterial hypertension (PAH). Announced Research Updates TG Therapeutics announced interim data from the 420 patient, Phase III UNITY-CLL trial, where patients treated with ublituximab plus umbralisib had an improved progression free survival compared to obinutuzumab plus chlorambucil in patients with previously untreated and relapsed/refractory chronic lymphocytic leukemia (CLL). Due to the results, the trial was ended early. Akebia announced that in the 36-week, 369 patient, Phase III, INNO2VATE Correction/Conversion trial, vadadustat was non-inferior to darbepoetin in the change in hemoglobin (0.17 g/dL difference) and hemoglobin level (10.36 vs 10.53 g/dL) in patients with chronic dialysis for end-stage renal disease. Akebia announced that in the 36-week, 3,554 patient, Phase III, INNO2VATE Conversion trial, vadadustat was non-inferior to darbepoetin in the change in hemoglobin (0.31 g/dL difference) and hemoglobin level (10.36 vs 10.61 g/dL) in patients with chronic dialysis for end-stage renal disease. In the two INNO2VATE Correction/Conversion and Conversion trials, vadadustat was non-inferior to darbepoetin in the incidence of MACE (composite endpoint of all-cause mortality, non-fatal myocardial infarction, or non-fatal stroke). Ovid announced that in the 12-week, 23 patient, Phase II ROCKET trial, treatment with gaboxadol resulted in a 26.2% improvement in the Aberrant Behavior Checklist-Community for Fragile X syndrome (ABC-CFXS) score and a 21.6% mean improvement in the Anxiety, Depression and Mood Scale (ADAMS) total score in patients with Fragile X syndrome. Published Research Updates In a 65 patient, Phase II trial, patients treated with voxtalisib plus pimasertib, the objective response rate (ORR) was 9.4% compared to 12.1% with pimasertib monotherapy in patients with recurrent unresectable borderline/low malignant potential or low-grade serous ovarian carcinoma. The trial was terminated early because over half of the patients in both arms discontinued treatment and the ORR was considered too low. In the 150 patient, Japanese PELTA trial, prophylactic landiolol for four days after surgery did not reduce the incidence of postoperative atrial fibrillation in post-cardiac surgery patients who were 70 years or older. In a 12-week, 257 patient, Phase II trial, treatment with estetrol 15 mg decreased the severity of hot flushes (HFs) compared to placebo (-1.04 vs -0.66) in postmenopausal women with seven or more moderate to severe HFs per day or 50 or more moderate to severe HFs weekly. Between now and the end of the year there are twenty-six drugs in line for FDA approval. Four of them are due prior to the end of this quarter:
Regulatory Update
The FDA approved opicapone (Ongentys, Neurocrine Bioscience) on 4/27/2020, as add-on therapy to levodopa/carbidopa in patients with Parkinson's disease experiencing "off" episodes. The FDA accepted the NDA for terlipressin (Lucassin, Mallinckrodt, Biovie) to treat hepatorenal syndrome type 1 (HRS-1) and set a PDUFA date of 9/12/2020. The EMA accepted the Marketing Authorization Application (MAA) for lonafarnib (Sarasar, Eiger BioPharmaceuticals, Merck) for the treatment of Hutchinson-Gilford Progeria Syndrome (HGPS or Progeria) and Progeroid Laminopathies. Chimerix began a rolling NDA for brincidofovir as a treatment for smallpox and expects to complete it by mid-2020. Announced Research Updates Roche announced that in the 12-month, 41 patient, Phase III, open-label FIREFISH trial, 29.3% (12/41) of infants treated with risdiplam were able to sit without support for at least five seconds, assessed by the Gross Motor Scale of the Bayley Scales of Infant and Toddler Development Third Edition (BSID-III) compared to none in a historical control cohort of infants with Type 1 spinal muscular atrophy. Novartis announced that in the 97 patient, Phase II, Geometry mono-1 trial, treatment with capmatinib resulted in an overall response of 40.6% in the pre-treated group and 67.9% in the treatment-naive group in patients with metastatic MET exon 14 skipping non-small cell lung cancer. In 13 patients with brain metastases, 7/13 (54%) had an intracranial response with four patients having a complete resolution of all brain lesions. Published Research Updates In a 4-week, 1,432 patient, open label trial, 70.5% of patients treated with nabiximols had a decrease in at least one spasticity-related symptom in patients with multiple sclerosis drug-resistant spasticity. This observational study was performed in Italy, where the drug is already approved. In a 48-week, 48 patient, phase II trial, treatment with ublituximab resulted in median B cell depletion of > 99%, a decrease in mean T2 lesion volume of 10%, and an annualized relapse rate of 0.07, with 93% of patients with relapsing multiple sclerosis being relapse free. In the 25 patient, Phase II, open-label, PIKTAM trial, treatment with buparlisib plus tamoxifen resulted in a progression-free survival rate at 6-months of 33.3% in patients with hormone receptor-positive, HER2-negative advanced breast cancer previously treated with hormone therapy. The PIKTAM trial was originally designed to enroll 99 patients, but was terminated early due to liver toxicity observed in the BELLE-2 trial. |
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