Pipeline News and Updates
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Regulatory Update
The FDA approved vosoritide (Voxzogo, BioMarin) on 11/19/2021, to treat achondroplasia with open epiphyses in children five years of age and older. Note: Our subscribers have access to a vosoritide drug review. Subscribe and get access to 938 drug monographs and 21 drug reviews) The FDA granted a Fast Track Designation to omaveloxolone for the treatment of Friedreich’s ataxia. Announced Research Updates Mesoblast announced that in the 30-month, 565 patient, Phase III, DREAM-HF trial, treatment with a single dose of rexlemestrocel-L added to standard of care did not reduce the cumulative rate of recurrent non-fatal decompensation heart failure events compared to standard of care alone in patients with chronic heart failure with reduced ejection fraction. PhaseBio announced interim results from 150 patients enrolled in the Phase III REVERSE-IT trial, where treatment with bentracimab reduced PRU by 135% within four hours and 98.4% of patients achieved effective hemostasis within 24 hours in ticagrelor patients requiring urgent surgery or an invasive procedure or experiencing uncontrolled major or life-threatening bleeding. UCB announced interim data after from the 16-week, 852 patient, Phase III, BE OPTIMAL trial, where more paints treated with bimekizumab achieved ACR50 compared to placebo in patients with psoriatic arthritis, who have not been treated with a biologic drug. Daiichi Sankyo announced that in the 539 patient, Phase III, QuANTUM-First trial, adding quizartinib to standard induction and consolidation chemotherapy, then continuing quizartinib alone as maintenance therapy improved overall survival compared to standard treatment alone plus placebo maintenance therapy in patients with newly diagnosed FLT3-ITD positive acute myeloid leukemia (AML) Published Research Updates ICER found the evidence of a health benefit for adding mavacamten to optimal treatment of heart failure promising but inconclusive compared to optimal therapy alone or adding the drug to disopyramide. Some concern was expressed for the long-term effects of reduction in left ventricular ejection fraction and myocardial thickness. Some analysts have forecast an annual cost for mavacamten of $75,000, but ICER estimated a health-benefit price benchmark (HBPB) of $12,000-$15,000. Myectomy and septal ablation were found to be more cost effective than mavacamten. In the 14-day, 1,242 patient, Phase II, AXIOMATIC-TKR trial, venous thromboembolism developed in 21% of patients treated with milvexian 25 mg BID, 11% with 50 mg BID, 9% with 100 mg BID, 8% with 200 mg BID, 25% with 25 mg QD, 24% with 50 mg QD and 7% with 200 mg QD compared to 21% who received enoxaparin QD in patients undergoing knee arthroplasty. In a three-year, 18 patient, Phase I/II trial, treatment with SPK-8011 resulted in continued factor VIII expression in 16 of 18 participants and the annualized bleeding rate decreased from 8.5 events per year to 0.3 events per year, a 91.5% decrease, in patients with Hemophilia A. Published in the same issue of Lancet Gastroenterology last week:
Regulatory Update
The FDA approved ropeginterferon alfa-2b (Besremi, PharmaEssentia), on 11/12/2021, for the treatment of polycythemia vera. Ropeginterferon alfa-2b was approved with a Black Box Warning regarding fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. The FDA placed a hold on the giroctocogene fitelparvovec Phase III, AFFINE trial, in hemophilia A patients, to allow time to review changes to the trial’s protocol after high factor VIII levels were found in some treated patients. Announced Research Updates Compass Pathways announced that in a 12-week, 233 patient, Phase IIb clinical trial, treatment with psilocybin 25 mg decreased the MADRS by 6.6 points more than a 1 mg dose, at week three, in patients with treatment-resistant depression. The 10 mg dose was not significantly different from 1 mg. There was no placebo arm in the study. Madrigal announced results from 171 patients enrolled in the 52-week, open-label portion of the 1,200 patient, Phase III, MAESTRO-NAFLD-1 trial, where treatment with resmetirom reduced the MRI-proton density fat fraction (MRI-PDFF) by > 50%, liver volume by > 20% and fibrosis compared to placebo in patients with non-cirrhotic NASH. BMS announced 48-week data from 43 patients enrolled in the Phase II MAVERICK-LTE trial, a long-term extension of the MAVERICK-HCM trial, where treatment with mavacamten resulted in a 67% reduction of NT-proBNP. In a draft analysis of tirzepatide for the treatment of type 2 diabetes, ICER found that treatment with tirzepatide reduced HbA1c and weight more than background therapy. Analyzing data from a direct comparison with semaglutide and a network meta-analysis with empagliflozin, tirzepatide has a greater decrease in HbA1c and weight loss compared to empagliflozin. While semaglutide and empagliflozin have shown improvement in cardiovascular (CV) outcomes, the tirzepatide CV outcomes trial has not been completed. Due to the lack of the CV outcomes data, ICER found tirzepatide to provide comparable or better net health benefits to semaglutide and empagliflozin. Using the same price for tirzepatide as semaglutide, ICER found tirzepatide to have a QALY < $100,000 when compared to empagliflozin and less costly and less effective compared to semaglutide. Published Research Updates In the 52-week, 191 patient, Phase II, SERENITY trial, a 50% reduction in the severity in the Simple Endoscopic Score for Crohn's Disease (SES-CD) was achieved at week 12 by 25.8% of patients treated with mirikizumab 200 mg, 37.5% with 600 mg and 43.8% with 1,000 mg compared to 10.9% with placebo in patients with moderate to severe Crohn's disease. Mirikizumab responders were re-randomized to continue their IV induction dose or receive mirikizumab 300 mg subcutaneously every four weeks. After 52-weeks, 58.5% of IV patients maintained a 50% reduction in SES-CD compared to 58.7% who received the subcutaneous dose. In a six-week, 260 patient, Phase II trial, treatment with ansofaxine decreased the HAMD17 score compared to placebo in major depressive disorder. In the 144 patient, Phase III, E2902 trial, treatment with tipifarnib did not improve disease-free survival compared to observation in patients with acute myeloid leukemia in remission. Regulatory Update
The FDA extended the PDUFA date for ciltacabtagene autoleucel (cilta-cel) to 2/8/2022 to allow time to review newly submitted information describing an updated analytical method. In a review of carbetocin nasal spray, the FDA did not find evidence to support efficacy in the treatment of hyperphagia, anxiety, and distress behaviors associated with Prader-Willi Syndrome. The FDA’s Psychopharmacologic Drugs Advisory Committee agreed with the FDA review and voted 12 to 1 to reject intranasal carbetocin. The FDA accepted the BLA for toripalimab, in combination with gemcitabine and cisplatin, for the treatment of patients with recurrent or metastatic nasopharyngeal carcinoma and set a PDUFA date for 4/1/2022. Amylyx Pharmaceuticals submitted an NDA for AMX0035 to treat amyotrophic lateral sclerosis. In a revised analysis, ICER found tezepelumab to reduce the annualized asthma exacerbation rate compared to non-biologic standard of care in patients with severe, uncontrolled asthma. In patients with eosinophilic and non-eosinophilic asthma, the benefit was smaller than what is considered clinically important. ICER found tezepelumab to be comparable to inferior to dupilumab in patients with steroid-dependent asthma, but insufficient evidence to compare tezepelumab to omalizumab in patients with eosinophilic asthma. ICER has estimated a health-benefit price benchmark (HBPB) range for tezepelumab of $9,000 to $12,100 per year to achieve a QALY between $100,000 and $150,000 per year. Announced Research Updates Cortexyme announced that in the 48-week, 643 patient, Phase II/III, GAIN trial, treatment with atuzaginstat did not slow the decline in cognitive function (ADAS-Cog11 and ADCS-ADL) compared to placebo in patients with mild-to-moderate Alzheimer’s disease. However, in 242 patients with P. gingivalis DNA detectable in saliva, there was a 57% slowing of decline in ADAS-Cog11 with 80 mg and a 42% slowing of decline with 40 mg. There was no change in the decline of ADCS-ADL. Rafael announced that in the 528 patient, Phase III AVENGER 500 trial, adding devimistat to modified FOLFIRINOX did not improve overall survival compared to mFOLFIRINOX alone in patients with metastatic adenocarcinoma of the pancreas. Rafael announced the Phase III ARMADA 2000 trial was discontinued when an interim analysis found that adding devimistat to high dose cytarabine and mitoxantrone did not improve OS compared to high dose cytarabine and mitoxantrone alone in patients with relapsed or refractory acute myeloid leukemia. Devimistat also did not improve OS compared to mitoxantrone, etoposide and cytarabine or fludarabine, cytarabine, and filgrastim. Published Research Updates In the 12-week, 23 patient, Phase IIa ROCKET trial, 60% of patients treated with gaboxadol improved their Clinical Global Impressions-Improvement scale score in patients with Fragile X syndrome. After 16-weeks in the 26-week, 277 patient, Phase III ECZTRA 7 trial, 64.2% of patients treated with tralokinumab plus as needed topical corticosteroids achieved EASI-75 score compared to 50.5% with as needed topical corticosteroids alone in patients with severe atopic dermatitis who were not adequately controlled with or tolerant to cyclosporine. In a three-year long-term extension of the VITAL trial, overall survival was 70% in patients treated with gemogenovatucel-T compared to 40% with placebo. RFS also showed benefit with gemogenovatucel-T. In the 12-month, 97 patient, Phase II, LAICA trial, a 24-hour monthly infusion of levosimendan did not decrease rehospitalization for acute decompensated heart failure compared to placebo in patients with advanced heart failure. In the 52-week, 2,964 patient, open label, Phase III, ASCEND-D trial, patients treated with daprodustat achieved an increase in hemoglobin of 0.28 g/dL compared to a 0.1 g/dL increase with epoetin or daprodustat in CKD patients who were undergoing dialysis. In the 52-week, 3,872 patient, open label, Phase III, ASCEND-ND trial, patients treated with daprodustat achieved an increase in hemoglobin of 0.74 g/dL compared to a 0.66 g/dL increase with epoetin or daprodustat in CKD patients who were undergoing dialysis. DBV Technologies announced that in a 2.5 year extension of the REALISE trial (1,093 total days of exposure to an epicutaneous peanut patch), most children experienced a mild or moderate ADR with the most common being pruritus and application-site erythema. Regulatory Update
The FDA approved asciminib (Scemblix, Novartis ), on 10/29/2021, to treat resistant Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP). Asciminib was also approved for use in patients with Ph+ CML-C with a T315I mutation. Lilly and Pfizer discontinued development of tanezumab in October 2021 after rejections from the FDA and EMA. Lilly initiated a rolling BLA submission for donanemab to slow progression of Alzheimer’s Disease in October 2021. Lilly plans to compare donanemab to aducanumab in brain amyloid plaque clearance in early symptomatic Alzheimer's disease in the Phase III TRAILBLAZER-ALZ 4 trial. Announced Research Updates Cortexyme announced that in the 48-week, 643 patient, Phase II/III, GAIN trial, treatment with atuzaginstat did not slow the decline in cognitive function (ADAS-Cog11 and ADCS-ADL) compared to placebo in patients with mild-to-moderate Alzheimer’s disease. However in 242 patients with P. gingivalis DNA detectable in saliva, there was a 57% slowing of decline in ADAS-Cog11 with 80 mg and a 42% slowing of decline with 40 mg. There was no change in the decline of ADCS-ADL. Rafael announced that in the 528 patient, Phase III AVENGER 500 trial, adding devimistat to modified FOLFIRINOX did not improve overall survival compared to mFOLFIRINOX alone in patients with metastatic adenocarcinoma of the pancreas. Rafael announced the Phase III ARMADA 2000 trial was discontinued when an interim analysis found that adding devimistat to high dose cytarabine and mitoxantrone did not improve OS compared to high dose cytarabine and mitoxantrone alone in patients with relapsed or refractory acute myeloid leukemia. Devimistat also did not improve OS compared to mitoxantrone, etoposide and cytarabine or fludarabine, cytarabine, and filgrastim. Published Research Updates In the 12-week, 23 patient, Phase IIa ROCKET trial, 60% of patients treated with gaboxadol improved their Clinical Global Impressions-Improvement scale score in patients with Fragile X syndrome. After 16-weeks in the 26-week, 277 patient, Phase III ECZTRA 7 trial, 64.2% of patients treated with tralokinumab plus as needed topical corticosteroids achieved EASI-75 score compared to 50.5% with as needed topical corticosteroids alone in patients with severe atopic dermatitis who were not adequately controlled with or tolerant to cyclosporine. In a three-year long-term extension of the VITAL trial, overall survival was 70% in patients treated with gemogenovatucel-T compared to 40% with placebo. RFS also showed benefit with gemogenovatucel-T. In the 12-month, 97 patient, Phase II, LAICA trial, a 24 hour monthly infusion of levosimendan did not decrease rehospitalization for acute decompensated heart failure compared to placebo in patients with advanced heart failure. |
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