Regulatory Update
FDA approved sparsentan (Filspari, Travere Therapeutics), on 2/17/2023, to reduce proteinuria in adults with primary IgAN at risk of rapid disease progression. Sparsentan was approved under an accelerated approval pathway and further efficacy evidence is required for full approval. Sparsentan was approved with a boxed warning for hepatotoxicity and birth defects. The FDA approved efanesoctocog alfa (Altuviiio, Sanofi & Sobi), on 2/23/2023, for routine prophylaxis, on-demand treatment and control of bleeding episodes, and perioperative management of bleeding in patients with hemophilia A. The FDA rejected omecamtiv mecarbil for the treatment of heart failure with reduced ejection fraction (HFrEF) and requested an additional heart failure trial. Cytokinetics has decided not to conduct a second trial and will instead focus on development of aficamten a next generation cardiac myosin inhibitor being evaluated for obstructive hypertrophic cardiomyopathy (HCM). The FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) voted 7 to 4 on effectiveness and 7 to 4 on safety, , with 1 abstention in each vote, to recommend approval of Pfizer’s respiratory syncytial virus vaccine in patients 60 years and older. The VRBPAC expressed concern regarding the low number of high risk patients, patients over 80 and co-administration with influenza vaccines. They also wanted to see additional long-term data. Both VRBAC and the FDA expressed concerns for a potential risk of Guillain-Barre syndrome. The FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) voted unanimously 12-0 on effectiveness and 10-2 on safety for GSK’s respiratory syncytial virus vaccine in patients 60 years and older. The committee noted the vaccine had been studied in immunocompromised patients and co-administered with influenza vaccinations. They would like to see more long-term data and use in patients over 80. The FDA accepted the BLA and the EMA accepted the MAA for elranatamab for the treatment of relapsed or refractory multiple myeloma. A decision is expected before the end of 2023. The FDA accepted the NDA for avacincaptad pegol to treat geographic atrophy secondary to dry age-related macular degeneration and set a PDUFA date for 8/19/2023. The FDA accepted the BLA for pozelimab for the treatment of CHAPLE disease and set a PDUFA date for 8/20/2023. The FDA accepted the BLA for cosibelimab for the treatment for metastatic cutaneous squamous cell carcinoma and set a PDUFA date for 1/3/2024. The FDA accepted the BLA for Valneva’s chikungunya vaccine, VLA1553 and set a PDUFA date for late August 2023. The FDA is extending the PDUFA date by three months for fezolinetant to allow more time to complete the review. The new date is 5/22/2023. The FDA accepted the NDA for nirogacestat for the treatment of adults with desmoid tumors and set a PDUFA date for 8/27/2023. The FDA designated mRNA-4157/V940 in combination with pembrolizumab a Breakthrough Therapy for the adjuvant treatment of high-risk melanoma following complete resection. CHMP has recommended approval of pegunigalsidase alfa for the treatment of Fabry disease. Announced Research Updates Three gene therapies to treat sickle cell disease were recently discontinued.
Inovio announced that in the 36-week, 203 patient, Phase III REVEAL 2 trial, treatment with VGX-3100 did not improve lesion regression or viral clearance compared to placebo in a biomarker identified subset of 25 patients with HPV-16/18-associated cervical HSIL. The biomarker population was supposed to identify patients more likely to respond to VGX-3100. However, there was a significant improvement with VGX-3100 in the overall population (27.6% vs 8.7%). Amicus announced data from 118 patients for up to 104 weeks from an open-label extension of the PROPEL trial, where improvements in 6MWD and lung function were maintained with cipaglucosidase alfa/miglustat treatment. EMD Serono announced that after 228 weeks in an open-label extension of a Phase II trial, the ARR was 0.13 in patients with relapsing multiple sclerosis. Patients who switched from 75mg QD to BID had a reduction in their ARR from 0.19 to 0.10. Immunic announced that in the 24-week, 268 patient, Phase II EMPhASIS trial, 1.6% of patients treated with vidofludimus experienced 12-week Confirmed Disability Worsening (12wCDW) compared to 3.7% of patients who received placebo in patients with relapsing-remitting multiple sclerosis. Data from up to 180-weeks was available from 209 patients enrolled in a long-term, open-label extension of the EMPhASIS trial, where treatment with vidofludimus resulted in 97.6% of patents to be free of 12wCDW at 48-weeks and 94.5% were free of 12wCDW at 96 weeks. Similar results were seen for 24-week CDW at both time periods. Published Research Updates A draft review by ICER found a high likelihood that resmetirom is at least comparable with the current standard of care with some evidence to support a health benefit. The data was found to be limited given the short duration of the trials compared to the slow long-term progression of the disease. It was also noted that many patients do not develop symptomatic disease. Using an annual placeholder cost of $19,000, resmetirom was found to be cost effective. In the 41 patient, Phase II CALYPSO trial, savolitinib plus durvalumab resulted in a confirmed response rate (cRR) of 29%, which missed the target of at least 50% in patients with metastatic papillary renal cell carcinoma. The cRR was 53% in a subset of MET-driven patients (n/N = 9/27) and 33% in a subset of PD-L1-positive patients (n/N = 9/27). After 104 weeks in the Phase III, open-label, GENEr8-1 trial, valoctocogene roxaparvove lowered the annualized bleeding rate by 84.5% in men with severe hemophilia A. In the 15-day, 581 patient, Phase III, MOUNTAIN trial, treatment with zuranolone did not improve the HDRS-17 score compared to placebo (12.5 vs 11.1) in patients with major depressive disorder. In the six-month, 64 patient, Phase III, VANGUARD trial, patients treated with garadacimab experienced 0.27 HAE attacks per month compared to 2.01 with placebo in patients with hereditary angioedema. New Drugs Added to Knowledgebase
We recently added six new drugs to the knowledgebase:
Regulatory Update The FDA rejected the NDA for SGX301 for the treatment of early-stage cutaneous T-cell lymphoma and requested additional information. The FDA designated rexlemestrocel-L, a Regenerative Medicine Advanced Therapy (RMAT) for in the treatment of chronic low back pain associated with disc degeneration, in combination with hyaluronic acid (HA) as delivery agent for injection into the lumbar disc. Announced Research Updates Galapagos announced that in the 58-week, 1,374 patient, Phase III, DIVERSITY trial, treatment with filgotinib did not induce remission at 10-weeks compared to placebo in patients with moderate to severe Crohn's disease. In the maintenance phase, remission at 58 weeks was achieved by 43.8% of patients treated with filgotinib 200 mg and 26.4% with placebo. 30.4% of filgotinib 200 mg patients had an endoscopic response compared to 9.4% with placebo during the maintenance phase. G1 Therapeutics announced that in the 326 patient, Phase III, PRESERVE 1 trial, adding trilaciclib to FOLFOXIRI plus bevacizumab decreased the occurrence of severe neutropenia (1% vs 20%) and duration of severe neutropenia (0.1 day vs 1.3 days) compared to placebo in patients with metastatic colorectal cancer. However the overall response rate (ORR) was higher with placebo (61% and 50%). GI Therapeutics discontinued the PRESERVE 1 trial after the overall response rate was found to be higher with trilaciclib compared to placebo. AlloVir announced that in a 24-week, 52 patient, Phase II trial, treatment with posoleucel resulted in greater BK viral load reduction than placebo in kidney transplant patients with BK viremia. Applied Therapeutics announced 90-day interim data from the 50 patient, Phase III, INSPIRE trial, where treatment with gavorestat reduced sorbitol levels 52% compared to placebo in patients with Sorbitol Dehydrogenase (SORD) Deficiency. Published Research Updates In a 12-week, 229 patient, Phase II trial, the increase in left ventricular ejection fraction (LVEF) was similar for firibastat 100 mg (5.3%), firibastat 200 mg (5.3%) and ramipril 5 mg (5.7%) in post anterior myocardial infarction patients. In the 24-week, 263 patient, open-label, Phase III, ECOSPOR IV trial, 8.7% of patients treated with SER-109 experienced a recurrence of C. difficile infection at eight weeks in patients with recurrent C. difficile infection. After 24 weeks 86.3% of patients treated maintained a sustained clinical response. In a 24-week, 366-patient Phase IIb trial, adding OPT-302 2 mg to ranibizumab resulted in a 14.2 letter improvement in Best Corrected Visual Acuity (BCVA) compared to an 10.8 letter improvement with ranibizumab monotherapy in patients with wet age-related macular degeneration (AMD). There was no improvement in BCVA with the 0.5 mg dose. In the 5,782 patient, Phase IIb, CYPRESS trial, J&J’s RSV vaccine achieved vaccine efficacy of 80% to prevent three or more symptoms of lower respiratory tract infection, 75% to prevent two or more symptoms of lower respiratory tract infection and 69.8% to prevent either two or more symptoms of lower respiratory tract infection or one or more symptoms of lower respiratory tract infection plus at least one systemic symptom in patients 65 years and older. COVID-19 Update In the 28-day, 1,951 patient, Phase III TOGETHER trial (NCT04727424), 2.7% of patients treated with peginterferon lambda were hospitalized or had an ER visit compared to 5.6% with placebo in non-hospitalized adult Brazilian patients with COVID-19. 83% of the patients had received at least one COVID-19 vaccination. Regulatory Update
The FDA approved daprodustat (Jesduvroq, GSK), on 2/1/2023, to treat anemia in chronic kidney disease patients on dialysis. Daprodustat was approved with a boxed warning of the increased risk of increased risk of death, myocardial infarction, stroke, venous thromboembolism, and thrombosis of vascular access. The FDA accepted the NDA for zuranolone for the treatment of major depressive disorder and postpartum depression and set a PDUFA date for 8/5/2023. Mesoblast resubmitted a BLA for remestemcel-L to treat pediatric steroid-refractory acute graft versus host disease. Roche discontinued development of ipatasertib and gantenerumab due to lack of efficacy. In February 2023, Vistagen proposed changes to the PALISADE-2 study protocol to the FDA. Vistagen is also designing a new Phase III trial that would include multiple doses of PH94B and use the the Liebowitz Social Anxiety Scale (LSAS) as the primary endpoint. The outcome of a meeting with the FDA will determine when the PALISADE-2 trial would be restarted. Announced Research Updates Roche announced that in the 25-week, 200 patient, open-label, Phase III COMMODORE 2 trial, treatment with crovalimab was non-inferior to eculizumab in achievement of an LDH of 1.5 or less of the upper limit of normal and being RBC transfusion free in non-U.S. patients with PNH who have not been previously treated with complement inhibitors. Published Research Updates In a 96-week, 453 patient, Phase II trial, treatment with tilavonemab did not improve the Clinical Dementia Rating-Sum of Boxes score compared to placebo in patients with early Alzheimer's disease. Regulatory Update
The FDA approved elacestrant (Orserdu, Stemline Therapeutics), on 1/27/2023, for the treatment of estrogen receptor–positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy. The FDA approved pirtobrutinib (Jaypirca, Lilly), on 1/27/2023, for the treatment of relapsed or refractory mantle cell lymphoma after at least two lines of systemic therapy, including a Bruton's tyrosine kinase inhibitor. The FDA’s Antimicrobial Drugs Advisory Committee voted 14 to 1 to recommend approval of rezafungin for the treatment of candidemia and invasive candidiasis. The FDA accepted the NDA for gepirone or the treatment of major depressive disorder and set a PDUFA date of 6/23/2023. The FDA granted Moderna’s mRNA vaccine, mRNA-1345, a Breakthrough Therapy Designation for the prevention of RSV-associated lower respiratory tract disease in adults aged 60 years or older. The EMA validated the MAA for exagamglogene autotemcel, initiating a full review by CHMP. CHMP recommended that palovarotene to treat fibrodysplasia ossificans progressiva not be approved by the EMA. Announced Research Updates Deciphera announced that in a 453 patient, open-label, Phase III, INTRIGUE trial, treatment with ripretinib did not improve PFS compared to sunitinib in patients with GIST previously treated with imatinib. Peregrine announced that in a 28 patient, Phase II trial, treatment with bavituximab plus pembrolizumab resulted in an ORR of 32.1% in patients with previously untreated advanced hepatocellular carcinoma. Published Research Updates In the 52-week, 159 patient, Phase III, XTEND-1 trial, once weekly treatment with efanesoctocog alfa resulted in an annualized bleeding rate of 0.71 in 133 patients with severe hemophilia A. 26 patents in XTEND-1 received on-demand efanesoctocog alfa and 97% of bleeding episodes resolved after one injection of efanesoctocog alfa. 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. In the 24-week, 195 patient, Phase III, MOMENTUM trial, 25% of patients treated with momelotinib achieved a reduction of at least 50% in their Myelofibrosis Symptom Assessment Form (MFSAF) TSS compared to 9% with danazol in patients with myelofibrosis who were symptomatic and anemic and had been previously treated with an FDA-approved JAK inhibitor. We recently added 3 new drugs to the knowledgebase:
The Prescribe Right Pharmaceutical Pipeline Tracker now allows you to track 1,113 pipeline and recently approved drugs supported by 2,952 announced and published study results. Regulatory Update
The FDA approved bexagliflozin (Brenzavvy, TheracosBio), on 1/20/2023, to improve glycemic control in adults with type 2 diabetes mellitus as an adjunct to diet and exercise. The FDA granted granted tecarfarin a Fast Track designation for the prevention of systemic thromboembolism in patients with end-stage renal disease and atrial fibrillation. Finch discontinued the Phase III PRISM4 trial in January 2023, while the company examines the value of its intellectual property estate and other assets. The PRISM4 trial was evaluating CP101 in the prevention of recurrent C. difficile infection. Regulatory Update
Medexus and Medac estimate it will take up to a year to collect and submit all data requested by the FDA for the resubmitted NDA for treosulfan. Announced Research Updates Oramed announced that in the 26-week, 710 patient, Phase III, ORA-D-013-1 trial, oral insulin did not improve HbA1c or fasting plasma glucose compared to placebo in patients with type 2 diabetes that was not controlled by at least one antihyperglycemic agent. Published Research Updates In the 12-week, 153-patient, Phase IIb, D1AMOND trial, treatment with ecopipam reduced the YGTSS-TTS by 3.44 points compared to placebo in patients aged 6 to 17 years with Tourette syndrome. Subscribers received a total of EIGHT study results this week. Contact us today for a subscription. We recently added 25 new drugs to the knowledgebase:
The Prescribe Right Pharmaceutical Pipeline Tracker now allows you to track 1,111 pipeline and recently approved drugs supported by 2,934 announced and published study results Regulatory Update
The FDA approved lecanemab (Leqembi, Eisai & Biogen), on 1/6/2023, too slow the reduction in cognition in Alzheimer’s patients with mild cognitive impairment or mild dementia. Eisai & Biogen set WAC for at lecanemab $26,500 per year. The FDA accepted the BLA for nirsevimab for the prevention of respiratory syncytial virus (RSV) in newborns and infants with an approval decision anticipated in 3Q23. The FDA accepted the BLA for rozanolixizumab for the treatment of generalized myasthenia gravis in patients who are anti-acetycholine receptor or anti-muscle-specific tyrosine kinase antibody positive with an approval decision expected by the end of 2Q23 The FDA accepted the BLA for glofitamab for the treatment of relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy and set a PDUFA date for 7/1/2023. The FDA accepted the NDA for vamorolone for the treatment of Duchenne muscular dystrophy (DMD) and set a PDUFA date for 10/26/2023. The FDA has placed a hold on the launch of vonoprazan until acceptable levels of nitrosamine and met and maintained throughout the shelf-life of the product. Checkpoint Therapeutics submitted a BLA for cosibelimab for the treatment of metastatic cutaneous squamous cell carcinoma. Novan submitted an NDA for berdazimer gel for the treatment of molluscum contagiosum. The FDA granted an Orphan Drug Designation to azeliragon for the treatment of glioblastoma. Regulatory Update
The FDA approved lenacapavir (Sunlenca, Gilead Sciences), on 12/22/2022, for the treatment of HIV-1 infection in heavily treatment-experienced adults with multi-drug resistant HIV-1 infection. Lenacapavir is initiated as a combination of oral tablets with the first subcutaneous injection. After the loading dose, a subcutaneous injection of lenacapavir is given every six months. According to Endpoints News WAC for the first year of lenacapavir will be $42,250 with subsequent years costing $39,000. The FDA approved mosunetuzumab (Lunsumio, Genentech, Roche), on 12/22/2022, for the treatment of relapsed or refractory follicular lymphoma in patients who have received at least two previous systemic therapies. The FDA approved ublituximab (Briumvi, TG Therapeutics), on 12/28/2022, for the treatment of relapsing forms of multiple sclerosis in adults. The FDA delayed a decision on toripalimab, until a site inspection of the manufacturing facility can be completed. Due to COVID-19 related restrictions on travel in China, an inspection had not been competed in December 2022. The FDA rejected palovarotene and requested additional details on clinical trials in December 2022. The FDA accepted the resubmitted BLA for bimekizumab for the treatment of moderate to severe plaque psoriasis with approval expected in 2Q23. The FDA has placed a hold on the Phase III VITESSE trial, evaluating Viaskin Peanut, until DBV makes changes to the study protocol regarding statistical analysis and total number of patients. DBV modified the VITESSE protocol, and the FDA lifted the hold in December 2022. SpringWorks submitted an NDA for nirogacestat for the treatment of adults with desmoid tumors. Published Research Updates In a review of fezolinetant, ICER found evidence to support a health benefit for fezolinetant in the treatment of vasomotor symptoms to be insufficient compared to menopausal hormone therapy. Longer-term safety and efficacy data are needed to determine the place in therapy for fezolinetant. ICER estimated a Health Benefit Price Benchmark for fezolinetant to be $2,000 to $2,500 per year. ICER found evidence to support use of lecanemab to slow the development of mild cognitive impairment in early Alzheimer's disease to be promising but inconclusive with the possibility for harm due to ARIA. ICER estimated a range to meet cost-effectiveness criteria to be $8,500 to $20,600 per year. ICER found evidence to support use of donanemab to slow the development of mild cognitive impairment in early Alzheimer's disease to be insufficient, with only data from a Phase II trial available. There is also the with the possibility for harm due to ARIA. ICER assumed the drug would be as effective as lecanemab to estimate a range to meet cost-effectiveness criteria to be $14,500 and $46,900 per year. An ICER review concluded there was a moderate certainty of a comparable, small, or substantial health benefit with etranacogene dezaparvovec compared to factor IX therapy for the treatment of severe hemophilia B. While etranacogene dezaparvovec offers a clinical benefit, ICER was concerned about the duration of the benefit with long-term data only available through 18 months for 54 patients. There was also concern about potential long-term harms to liver function and hepatocellular carcinoma. ICER estimated a Health Benefit Price Benchmark (HBPB) of $2.93 million to $2.96 million for a single dose of etranacogene dezaparvovec. An ICER review concluded there was a moderate certainty of a comparable, small, or substantial health benefit with valoctocogene roxaparvovec compared to factor VIII prophylaxis for the treatment of severe hemophilia A without inhibitors. When comparing valoctocogene roxaparvovec to emicizumab, ICER found limitations due to the small amount of data available to compare the drugs. They concluded there was low certainty for a net health benefit with valoctocogene roxaparvovec compared to emicizumab. While valoctocogene roxaparvovec offers a clinical benefit, ICER was concerned about the duration of the benefit and potential long-term harms to liver function and hepatocellular carcinoma. ICER estimated a Health Benefit Price Benchmark (HBPB) of $1.96 million for a single dose of valoctocogene roxaparvovec. |
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