Update for January 5, 2022

Regulatory Update
 
The FDA approved inclisiran (Leqvio, Novartis), on 12/22/2021, as an adjunct to diet and maximally tolerated statin therapy for the treatment of atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH) in patients who require additional lowering of LDL-C. 

• Inclusiran is administered as a subcutaneous injection. A second dose of inclusiran is administered 3 months after the first dose, then the drug is given every six months. 
• Inclusiran lowers LDL by interfering with the RNA that leads to production of proprotein convertase subtilisin–kexin type 9 (PCSK9). 
• Alirocumab (Praluent) and evolocumab (Repatha) are monoclonal antibodies that bind to PCSK9 inhibiting it action and lowering LDL. The PCSK9 antibodies are given every 2-4 weeks depending on dosing. 
• The 54% reduction with inclisiran is similar to the 58% reduction alirocumab in the ODYSSEY trial and the 63% reduction with evolocumab in the FOURIER trial. 
• ICER estimated the annual cost for inclisiran to be $3,600 to $6,000 a year to be cost-effective. The range is similar to the price for the two PCSK9 monoclonal antibodies, evolocumab at $5,400 and alirocumab at $5,850.
• Novartis set WAC for inclusiran at $3,250 per dose so the initial year will cost $9,750 and subsequent years $6,500, which is high than ICER’s estimates and the annual cost for the two PCSK9 monoclonal antibodies.​

The FDA approved tralokinumab (Adbry, Leo Pharma ), on 12/28/2021, for the treatment of moderate-to-severe atopic dermatitis that is not adequately controlled with topical prescription therapies or when those therapies are not advisable. Tralokinumab can be used with or without topical corticosteroids.
 
The FDA approved levoketoconazole (Recorlev, Xeris Biopharma), on 12/30/2021, for the treatment of endogenous hypercortisolemia in patients with Cushing’s syndrome for whom surgery is not an option or has not been curative. Levoketoconazole was approved with a Black Box Warning regarding hepatotoxicity and QT prolongation.
 
The FDA placed a hold on HIV trials using Gilead’s injectable lenacapavir due to concerns regarding the compatibility of vials made of borosilicate glass with lenacapavir solution, which could potentially lead to the formation of sub-visible glass particles. The hold does not affect trials using the oral formulations of lenacapavir. 
 
The FDA accepted the NDA for Amylyx Pharmaceuticals’ AMX0035 for the treatment of amyotrophic lateral sclerosis(ALS) and set a PDUFA date for 6/29/2022.
 
Lexicon submitted an NDA for sotagliflozin to reduce the risk of cardiovascular complications in heart failure patients with type 2 diabetes. 
 
The FDA granted Biogen and Eisai’s lecanemab a fast-track designation as a treatment of early Alzheimer's disease.
 
Published Research Updates
 
In a 155 patient, Phase II trial, treatment with balstilimab and zalifrelimab resulted in a 25.6% objective response rate (ORR) in patients with recurrent and/or metastatic cervical cancer, who had relapsed after prior platinum-based chemotherapy. 
 
In the 28-day, 439 patient, Phase III, GRAVITAS-301 trial, adding itacitinib to corticosteroids did not improve the overall response rate compared to corticosteroids alone in patients with treatment-naive acute graft-versus-host disease.
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In a 28-week, 189 patient, Phase III trial, treatment with MSC-NTF did not improve the number of patients that achieved a 1.25 point improvement or > per month in their Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score compared to placebo (33% vs 28%) in patients with amyotrophic lateral sclerosis (ALS). 
 
In the 16-week, 332 patient, Phase III, BE MOBILE 2 trial, more patients treated with bimekizumab achieved ASA40 compared to placebo in patients with Ankylosing Spondylitis who had an inadequate response to an NSAID or TNF-inhibitor.
 
In the 92 patient, Phase III, REALITY trial, treatment with apatinib resulted in a PFS of 22.2 months compared to 4.5 months with placebo in patients with radioactive iodine-refractory differentiated thyroid cancer.
 
In the 127 patient, Phase III TreeTopp trial, adding varlitinib to capecitabine did not improve progression-free survival or overall response rate compared to capecitabine alone in patients with biliary tract cancer.