Take stock: Q1 is about to be approved for heavy-weight drugs in 2021

1, casimersen - PDUFA effective February 25, 2021 Duchy muscular dystrophy (DMD) is a rare and fatal neuromuscular genetic disease that occurs in one in every 3,500-5,000 men worldwide.
DMD is characterized by aggressive muscle degeneration and muscle weakness, which are caused by genetic mutations that affect the function of dystrophin proteins.
protein is a protein involved in maintaining muscle fiber integrity.
of DMD usually occur in infants and young children, affected children may experience stunting, such as walking, climbing stairs, or standing from a sitting position.
with the development of the disease, lower limb muscle weakness spread to the arms, neck and other parts.
most patients need to use a wheelchair full-time in their teens and then gradually lose the ability to do daily activities independently, such as using the bathroom, bathing and feeding.
end, increased breathing difficulties due to respiratory insfusion require breathing support, and heart failure can lead to heart failure.
the disease is widespread and fatal, and patients usually die of the disease in their 20s.
casimersen, developed by Sarepta Therapeutics, is a phosphate oligopolymer (PMOs) that alters the shearing process of the mRNA pregenitor by binding to the mRNA pregenitor, allowing the resulting mature mRNA to skip the 45 exons carrying the gene mutation.
Usually a genetic mutation on exons 45 causes antimyostrophic proteins to fail to produce, while casimersen therapy restores the production of antimyostrophic proteins, which, although missing amino acids encoded by exons No. 45, still have certain functions and can therefore alleviate symptoms in DMD patients.
2020, Sarepta Therapeutics submitted a new drug application (NDA) to the FDA through the FDA's accelerated approval process.
NDA includes data from a placebo-controlled Phase III clinical study called ESSENCE involving 43 DMD patients with genetic mutations that caused the dystrophin gene to skip the 45 exons, an estimated 8 percent of DMD patients.
an interim analysis after 48 weeks of treatment with casimersen showed a statistically significant (albeit modest) statistically significant increase in the expression of muscular dystrophy protein in the western blot test compared to baseline and placebo.
While it is debatable whether this small change in antimyostrophy protein levels can lead to clinical improvement, the FDA has previously approved Sarepta's PMOs therapies Vyondys 53 (golodirsen) and Exondys 51 (eteplirsen), both of which are based on small changes in myotrophy protein expression levels that promote exon jumps to compensate for different mutations in the muscular malnutrition protein gene.
the NDA of Casimersen was accepted and given priority review, and the prescription drug user charge act (PDUFA) came into effect on February 25, 2021.
Expanded Reading 1, Exondys 51 (eteplirsen) eteplirsen (trade name Exondys 51) is an antonysic RNA drug developed by Sarepta Therapeutics for the treatment of Duching's muscular dystrophy (DMD), which was approved by the FDA in September 2016 and is the first innovative FDA-approved treatment for specific DMD patients.
the cutting process of Exondys 51-targeted antimyostrophy protein mRNA preludes, designed to introduce exon 51 skipping to produce short but functional anti-myotrophy proteins.
statistics, about 13% of DMD patients carry genetic mutations suitable for exon 51 jump therapy.
Exondys 51 was approved for listing because it reached a number of biological endpoints in clinical trials, including the correct completion of RNA production levels for exon jumps, the expression of antimyostrophy proteins, and increased muscle strength.
three trials in the post-market study, Exondys 51 slowed the decline of lung function, regardless of the stage of the patient's development.
Exondys 51 is approved for use at a dose of 30 mg/kg, once a week, intravenously.
a 25kg child costs about $300,000 a year.
Exondys 51 generated $380 million in sales in 2019.
2, Vyondys 53 (golodirsen) golodirsen (trade name Vyondys 53) is an antisythrestic RNA drug developed by Sarepta Therapeutics for the treatment of Duching's muscular dystrophy (DMD), which was accelerated by the FDA in December 2019 and is the second INNOVATIVE treatment approved by the FDA for the treatment of specific DMD patients.
Vyondys 53 is suitable for patients with Duxing's muscular dystrophy (DMD) treated with exon 53 skipping.
Vyondys 53 targets the shearing process of the antimyostrophy protein mRNA prelude, introducing exon 53 jumps designed to produce short but functional antimyostrophy proteins.
, about 8% of DMD patients carry genetic mutations suitable for exon 53 jump therapy.
therapy is eligible for FDA-granted fast-track, orphan drug eligibility and priority review.
Vyondys 53 was evaluated in a two-part clinical study.
the first part of the program included 12 DMD patients, 8 patients treated with Vyondys 53, and 4 patients treated with placebos.
the second part of the open label trial, which included 12 patients in the first part and 13 new DMD patients.
study, patients' average muscular dystrophy protein levels increased from 0.1% (baseline) to 1.02% of normal levels after 48 weeks of treatment.
Exondys 51 is approved for use at a dose of 30 mg/kg, once a week, intravenously.
Vyondys 53 costs the same as Exondys 51.
2, umbralisib - PDUFA effective February 15/ June 15, 2021 Edge Zone Lymphoma (MZL) is a group of slow-growing mature B-cell non-Hodgkin's lymphoma (NHL).
MZL is generally considered a chronic incurable disease, and in the United States, MZL is the third most common B-cell NHL, accounting for about 8% of all NHL cases.
FL is a non-Hodgkin's lymphoma (NHL) that originates in B lymphocytes, and FL is the most common inert lymphoma, accounting for about 20 percent of all NHL cases.
umbralisib, developed by TG Therapeutics, is a new generation of small molecule inhibitors that are orally served once a day.
its specificity to PI3K is superior to other PI3K's inhibitors and does not inhibit PI3's.
and it can improve the drug's tolerance by inhibiting a protein called CK1, which prevents disruption of the function of regulatory T cells.
it has been recognized by the FDA as a breakthrough therapy for patients with lymphoma in marginal areas.
January 2020, TG Therapeutics submitted to the FDA an NDA supported by the unil-NHL clinical trial, a Phase II/III trial involving more than 200 NHL patients who had received at least two types of pre-treatment.
The trial achieved a goal of 40-50% of the main endpoints of total efficiency in two groups of patients, one with relapsed/incurable MZL and the other with third-line or later folytic lymphoma (FL).
the total efficiency of MZL group is 49%, the total efficiency rate is 16%, the total efficiency of FL group is 45%, and the total efficiency rate is 5%.
January 2019, umbralisib was awarded a breakthrough treatment designation for MZL, and in August 2020 umbralisib NDA for MZL patients was given priority review, with the PDUFA target date of February 15, 2021.
FL's NDA was awarded a standard review with a PDUFA target date of 15 June 2021.
2 umbralisib Profile 3, arimoclomol - PDUFA effective March 17, 2021 Niemann-Pick disease (NPC) also known as niephospholipid deposition disease, is a congenital glycolipid metabolic disease, is an endosomal recessive genetic disease.
NPC due to NPC1 or NPC2 gene mutations caused by the timely transfer of phospholipids from within the cells caused by accumulation, and then caused tissue damage, characterized by the total mononucleophageal and nervous system has a large number of foam cells containing neurophospholipids.
, there is no FDA-approved NPC treatment in the United States.
if approved, arimoclomol will be the first drug to treat NPC.
in Europe, Zavesca (miglustat, McGrath) was approved in 2009 and is the only drug to treat NPC.
in China, miglustat was approved for listing in 2017 under the name Zevico (Magsta Capsules) for the treatment of sexual neurosurgery in adult and child NPC patients.
arimoclomol is a small molecular compound of Orphazyme, a small molecule thermal shock stress-inducing agent that induces the expression of enhanced thermal shock proteins (HSPs).
can be quickly dispersed throughout the body after oral use and can pass through the blood-brain barrier and into the brain.
The drug works in stress cells by stimulating the cell's own thermal shock response, helping misfolded proteins to return to normal function, or by using the cell's recovery system, lysosomes, to recover these proteins from toxic accumulations when they are unable to return to normal function, which will help reduce the accumulation of misfolded proteins, which may be the cause of multiple diseases and symptoms.
3 arimoclomol molecular structure from the key Phase II/III randomized placebo-controlled trial (CT-ORZY-NPC-002) showed that arimoclomol played an active role in stabilizing the progression of the NPC nervous system, particularly in the subgroups of ≥-year-old patients and patients receiving miglustat (Magsta) as routine clinical care.
2 years of treatment, arimoclomol showed a continuous improvement in disease progress.
, patients who were initially randomly assigned a placebo had a 90 percent reduction in progress after turning to arimoclomol.
the FDA has set a target date for PDUFA at March 17, 2021.
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