Pipeline News and Updates
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Regulatory Update
The FDA approved naxitamab (Danyelza, Y-mAbs Therapeutics), on 11/25/2020, in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), for the treatment of relapsed or refractory high-risk neuroblastoma in bone or bone marrow. The FDA approved setmelanotide (Imcivree, Rhythm Pharmaceuticals), on 11/27/2020, for chronic weight management of obesity due to proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1) or leptin receptor (LEPR) deficiency confirmed by genetic testing. The FDA has delayed approval of Revance’s daxibotulinumtoxinA due to travel restrictions delaying the inspection of the manufacturing plant. A new PDUFA date has not been announced. The FDA rejected the NDA for Reata’s omaveloxolone for the treatment of Friedreich’s ataxia and requested additional data to strengthen data from the MOXIe trial. The EMA accepted the MAA for EMD Serono’s tepotinib for the treatment of metastatic non-small cell lung cancer harboring METex14 skipping alterations. Announced Research Updates Immunocore announced interim data from a 378 patient, Phase III trial, where treatment with tebentafusp resulted in estimated overall survival of 73% compared to 58% with investigator choice (82% pembrolizumab; 12% ipilimumab; 6% dacarbazine) in patients with metastatic uveal melanoma. UniQure announced that in the 26-week, 54 patient, Phase III, HOPE-B trial, a single dose of etranacogene dezaparvovec increased Factor IX activity from less than 2% at baseline to 37%. While 72% of patients reported no bleeding episodes, 15 patients reported 21 bleeding episodes in adult males with severe or moderate-severe Hemophilia B. Urovant announced that in a 12-week, 189 patient, Phase IIa trial, more patients treated with vibegron did not achieve at least a 30% improvement in average worst abdominal pain compared to placebo in women with abdominal pain due to irritable bowel syndrome (IBS) with IBS-D (diarrhea) and IBS-M (mixed IBS). Published Research Updates In a long term extension of the MUSE trial, 218 patients completed a total of 3 years of treatment with anifrolumab and maintained improvements in their SLE Disease Activity Index 2000 (SLEDAI-2K) scores and SLICC Damage Index (SDI) scores. In the 52-week, 455 patient, Phase III, ESAX-DN trial, 22% of patients treated with esaxerenone achieved urinary albumin-to-creatinine ratio remission (< 30 mg/g creatinine and or > 30% reduction) compared to 4% with placebo in Japanese patients with type 2 diabetes and urinary albumin-to-creatinine ratio of 45 to < 300 mg/g creatinine treated with renin-angiotensin system inhibitors. Regulatory Update
The FDA approved lonafarnib (Zokinvy, Eiger BioPharmaceuticals) on 11/20/2020, to reduce the risk of death due to Hutchinson-Gilford progeria syndrome and for the treatment of certain processing-deficient progeroid laminopathies in patients one year of age and older. The FDA approved lumasiran (Oxlumo, Alnylam Pharmaceuticals) on 11/23/2020, for the treatment of primary hyperoxaluria type 1 (PH1). The drug is well tolerated with the most common adverse effects being injection site reaction and abdominal pain. The EMA also approved lumasiran for the treatment of PH1. The FDA accepted the NDA for Apellis’ pegcetacoplan for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) and set a PDUFA date for 5/14/2021. The FDA designated ViiV’s cabotegravir a breakthrough therapy for the prevention of HIV infection. The FDA granted Sanofi’s rilzabrutinib a Fast Track designation for the treatment of immune thrombocytopenia. The FDA accepted the BLA for ADC Therapeutics’ loncastuximab tesirine for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and set a PDUFA date for 5/21/2021. Novartis has licensed the rights to develop and market remestemcel-L for the treatment of acute respiratory distress syndrome (ARDS). Amgen ended it collaboration with Cytokinetics for the development and commercialization of omecamtiv mecarbil. Announced Research Updates Eiger announced in the 24-week, 26 patient, Phase IIa, open-label, LIFT trial, 17 of 22 patients (77%) that completed 24 weeks of treatment with the combination of lonafarnib, ritonavir and pegylated interferon lambda achieved a > 2 log IU/mL decline in HDV RNA with a median decline of 3 log IU/mL in patients with a chronic infection of the hepatitis D virus. At Week 48 (24 weeks after completing treatment), 5/22 patients (23%) had HDV RNA below detection and 11 of 20 patients (55%) demonstrated improvement in Histology Activity Index (HAI). UniQure announced that in the 26-week, 54 patient, Phase HOPE-B trial, treatment with etranacogene dezaparvovec resulted in an increase in FIX activity from < 2% to 37.2% and 72% patients reporting no bleeding events in patients with hemophilia B. Elevar Therapeutics announced that in a 30 patient, Phase I/II trial, treatment with apatinib plus nivolumab resulted in an overall response rate of 13.3% in patients with locally advanced unresectable or metastatic solid tumors. Published Research Updates In a 16-week, 558 patient, Phase II/III trial, fasinumab 9 mg every four weeks and every eight weeks reduced the daily low back pain intensity numeric rating score compared to placebo in patients with moderate-to-severe, chronic low back pain. The 6 mg dose was no better than placebo. In the 24-month, 292 patient, Phase III, trial, patients treated with odanacatib increased lumbar bone mineral density by 5.6% more than placebo in men with osteoporosis. In the 76 patient Phase Ib/II ENCORE 601 trial, treatment with entinostat and pembrolizumab lead to an objective response rate (ORR) of 9.2%, which did not meet the prespecified ORR endpoint for positivity, in patients with non-small cell lung cancer In a 183 patient, Phase I, open-label, dose-ranging trial, treatment with loncastuximab tesirine resulted in an ORR of 45.6% in patients with relapsed or refractory B-cell non-Hodgkin lymphoma. Regulatory Update
The FDA rejected the BLA for Sanofi’s sutimlimab for the treatment of hemolysis in adult patients with cold agglutinin disease due to problems in a contracted manufacturing facility. The FDA rejected the BLA for Alkermes’ ALKS 3831 a combination of olanzapine and samidorphan) to treat schizophrenia due to tablet coating problems during manufacturing. The FDA has delayed approval of Bristol Myers Squibb’s lisocabtagene maraleucel due to travel restrictions delaying the inspection of the manufacturing plant. A new PDUFA date has not been announced. Announced Research Updates Pfizer announced that in the 52-week, 1,233 patient, Phase III, JADE REGIMEN trial, abrocitinib prevented an acute dermatitis flare (loss of at least 50% of the Eczema Area and Severity Index or EASI response seen at week 12 and an IGA score of two or higher) in 81.1% of patients treated with 200 mg and 57.4% of patients treated with 100 mg compared to 19.1% that received placebo in patients with moderate to severe atopic dermatitis. OncoSec Medical announced interim data from 54 patients enrolled in the Phase IIb, open -label, PISCES/KEYNOTE-695 trial, where treatment with tavokinogene telseplasmid plus pembrolizumab resulted in a 30% overall response rate in patients with unresectable stage III or IV metastatic melanoma. Amgen and AstraZeneca announced that in the 1,061 patient, 52-week, Phase III NAVIGATOR trial, treatment with tezepelumab reduced the annualized asthma exacerbation rate 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. Acceleron announced interim data from 10 patients enrolled in the 24-week, 25 patient, Phase II, open-label, SPECTRA trial, where treatment with sotatercept peak resulted in improvements in multiple hemodynamic measures as well as exercise tolerance and exercise capacity in patients with pulmonary arterial hypertension. MeiraGTx, announced 12-month interim data from a 10 patient, open-label, dose-escalation, Phase I/II trial, where treatment with AAV- RPGR resulted in an improvement in mean retinal sensitivity and low light visual mobility in patients with X-linked retinitis pigmentosa (XLRP). 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 achieved the ALSFRS-R improvement target compared to 27.7% with placebo. The study may have been underpowered due to more placebo patients achieving the ALSFRS-R improvement than anticipated. CymaBay announced that in the 3-month, 110 patient, Phase III, ENHANCE trial, 78.2% of patients treated with seladelpar 10 mg achieved a composite of a decrease in alkaline phosphatase and total bilirubin compared to 12.5% on placebo in patients with primary biliary cholangitis and an inadequate response or intolerance to ursodeoxycholic acid. CymaBay is evaluating seladelpar as a treatment for primary biliary cholangitis in the 52-week, 180 patient, Phase III RESPONSE trial (NCT04620733). BeyondSpring announced that in the 221 patient, Phase III PROTECTIVE 2 trial, grade 4 neutropenia was prevented in 31.5% of patients treated with plinabulin plus pegfilgrastim compared to 13.6% with pegfilgrastim alone in patients with breast cancer treated with docetaxel, doxorubicin, and cyclophosphamide. Published Research Updates In a 26-week, 243 patient extension of the Phase III trial, 43.5% of patients that continued ravulizumab and 40.3% of patients that switched from eculizumab to ravulizumab achieved LDH normalization. Transfusion was avoided in 73.6% of patients that continued ravulizumab and 67.2% of patients that switched from eculizumab to ravulizumab. In the 22-week, 8,256 patient, Phase III, GALACTIC-HF trial, 37% of patients treated with omecamtiv mecarbil experienced a composite endpoint of cardiovascular death or heart failure worsening compared to 39.1% with placebo in patients with symptomatic chronic heart failure and an ejection fraction of 35% or less. In the 516 patient, Phase III, SANDPIPER trial, patients treated with taselisib plus fulvestrant achieved progression-free survival of 7.4 months compared to 5.4 months with fulvestrant alone in patients with estrogen receptor-positive, HER-2-negative, PIK3CA-mutant locally advanced or metastatic breast cancer. In a 16-week, 272 patient, Phase II trial, the percentage points reduction in LDL over placebo with evinacumab was -56.0 with 450 mg weekly, -52.9 with 300 mg weekly, and -38.5 with 300 mg every two weeks in patients with refractory hypercholesterolemia. In the 9-month, 1,222 patient, Phase III, SOLOIST-WHF trial, 51% of patients treated with sotagliflozin experienced the composite endpoint of death from cardiovascular causes or hospitalization/urgent visits for heart failure compared to 76.3% with placebo in patients with diabetes and recent worsening heart failure. In the 16-month, 10,584 patient, Phase III, SCORED trial, patients treated with sotagliflozin experienced 5.6 events per 100 patient-years of the composite endpoint of total number of deaths from cardiovascular causes, hospitalizations for heart failure, and urgent visits for heart failure compared to 7.5 events per 100 patient-years with placebo in patients with diabetes and recent worsening heart failure. Both the 22-month SOLOIST-WHF trial and the 33-month SCORED trial were terminated early due to the COVID-19 pandemic and discontinuation of funding from Lexicon and Sanofi. Thank-you to active and veteran armed forces service men and women for your sacrifice.
Regulatory Update The FDA rejected SPN-812 (Viloxazine, Supernus Pharmaceuticals) for the treatment of ADHD, in November 2020, due to questions regarding analytical testing. The FDA Peripheral and Central Nervous System Drugs Advisory Committee voted 0 yes, 10 no and 1 uncertain on whether there was enough evidence to recommend approval of Biogen/Eisai’s aducanumab for the treatment of Alzheimer’s disease. The FDA accepted the NDA for BioMarin’s vosoritide for the treatment of achondroplasia and set a PDUFA date for 8/20/2021. The FDA will not have an advisory committee review the drug, but reminded BioMarin that it requested a two-year study in 2018. BioMarin feels that due to the positive outcome in a 121 patient, Phase III study and five-year data from Phase II trials, it has submitted enough data to warrant approval. The FDA requested additional information on Bluebird Bio’s beta beglogene darolentivec manufacturing, to prove analytical comparability between clinical-grade and commercial-grade manufacturing, therefore Bluebird has delayed submission of a BLA to late 2022. In September 2020, 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. In November 2020, Sarepta announced they would delay the Phase III trial and instead run a 10 patient, open-label trial to evaluate the safety and validate the commercial manufacturing process. The FDA has not indicated if the open-label trial would satisfy the requirements for approval or if the Phase III trial will be needed. Orphazyme submitted an MAA to the EMA for arimoclomol for the treatment of Niemann-Pick disease Type C (NPC). Announced Research Updates Aurinia announced that in the 12-week, 508 patient, Phase II/III, AUDREY trial, patients treated with voclosporin ophthalmic drops did not achieve an improvement in the Schirmer Tear Test at 4 weeks compared to placebo in patients with dry eye syndrome. Aurinia ceased development of voclosporin to treat dry eye syndrome after failure of the AUDREY trial. BMS announced that in the 16-week, 666 patient, Phase III, POETYK PSO-1 trial, more patients treated with deucravacitinib achieved PASI 75 and a Physician's Global Assessment (sPGA) score of 0 to 1 compared to apremilast in patients with moderate to severe psoriasis. BMS announced that in the 16-week, 180 patient, Phase II trial, 52.9% of patients treated with deucravacitinib 6 mg and 62.7% of patients treated with 12 mg achieved ACR-20 compared to 31.8% who received placebo in patients with psoriatic arthritis. Sanofi paused dosing in clinical trials for fitusiran, for treating Hemophilia and Hemophilia B, to investigate new adverse effects. Arena announced that in the 12-week, 140 patient, Phase IIb, ADVISE trial, treatment with etrasimod did not improve the Eczema Area and Severity Index (EASI) compared to placebo in patients with moderate-to-severe atopic dermatitis. ViiV announced the early discontinuation of the 3,223 patient, Phase III, HPTN 084 study, when an interim analysis demonstrated that treatment with cabotegravir injected every two months reduced the incidence of acquiring HIV compared to daily oral emtricitabine/tenofovir disoproxil fumarate (0.21% incidence compared to 1.79%) in patients at increased risk of HIV acquisition. Published Research Updates In an 8-week, 27 patient, Phase II trial, two day-long psilocybin sessions plus 11 hours of psychotherapy reduced the GRID-HAMD score from 22.8 to 8 (from moderate to mild depression) by week four, which was maintained through week eight, in patients with moderate-to-severe major depressive disorder. In a 2.5-year, 5,113 patient, open-label, long-term cardiovascular safety trial, treatment with LG Life Sciences/Sanofi’s gemigliptin resulted in a low incidence of cardiovascular ADR. The estimated incidence from Cox proportional hazard model was 1.35%. Regulatory Update
The FDA accepted the NDA for Pfizer’s abrocitinib for the treatment of moderate to severe atopic dermatitis in patients 12 and older. An April PDUFA date is expected. The EMA has also accepted the MAA for abrocitinib and a decision is anticipated in the second half of 2021. The EMA accepted the MAA for Biogen’s aducanumab for the treatment of Alzheimer’s disease. Announced Research Updates Kiniksa announced that in a 26-week, 70 patient, Phase II trial, 19% of patients treated with mavrilimumab experienced a giant cell arteritis flare compared to 46.4% with placebo in patients with giant cell arteritis. Galapagos and Gilead halted enrollment in filgotinib trials for the treatment of psoriatic arthritis, ankylosing spondylitis and uveitis until after they meet with the FDA to discuss FDA concerns regarding toxicity with the higher dose (200 mg). ChemoCentryx announced that in the 12-week, 398 patient, Phase II, AURORA trial, patients treated with neither avacopan 10 mg nor 30 mg achieved a Hidradenitis Suppurativa Clinical Response (HiSCR) compared to placebo in patients with moderate to severe Hidradenitis Suppurativa. Patients with severe disease, who were treated with avacopan 30 mg twice a day achieved a higher response than placebo. Amryt announced that in the 3-month, 218 patient, Phase III, EASE trial, 41.3% of patients treated with oleogel-S10 had complete closure of their target wound within 45 days compared to 28.9% with placebo in patients with Epidermolysis Bullosa. UCB announced that 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. Leo Pharma announced that in a 16-week, 258 patient, Phase IIb dose-ranging trial, patients treated with topical application of delgocitinib cream achieved an IGA score of clear or almost clear and a two point or greater improvement from baseline compared to placebo in patients with chronic hand eczema. Regeneron announced that the Independent Data Monitoring Committee paused the open-label portion of the 28-week, 44 patient, Phase II LUMINA-1 trial in October 2020, due to fatal serious adverse events with garetosmab in the trial. Published Research Updates In a 48-week, 82 patient, Phase II trial, patients treated with omaveloxolone had a 1.55 point reduction in their modified Friedreich's Ataxia Rating Scale (mFARS) scores compared to a 0.85 point increase with placebo in patients with Friedreich's ataxia. In a 61 patient, Phase II trial, administering trilaciclib before topotecan reduced the duration of severe neutropenia by five days compared to topotecan alone in patients with small cell lung cancer. In the 12-week, 42 patient, Phase II, CLASSIC trial, avacopan added to high dose prednisone and either cyclophosphamide or rituximab did not improve the Birmingham Vasculitis Activity Score (BVAS) by at least 50% compared to placebo in patients with ANCA-associated vasculitis (AAV). In a 12-month, 10 patient, Phase III, open-label trial, 80% of patients treated with setmelanotide achieved at least a 10% weight loss in patients with pro-opiomelanocortin deficiency obesity. In a 12-month, 11 patient, Phase III, open-label trial, 45% of patients treated with setmelanotide achieved at least a 10% weight loss in patients with leptin receptor deficiency obesity. Patients in both trials took the drug for 12 weeks and if they lost at least 5kg they went through an 8-week withdrawal period, followed by 32-weeks of open label treatment. |
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