New Drug

Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease associated with several known genetic abnormalities, including 17p deletion (del[17p]), 11q deletion (del[11q]), and TP53 gene mutations, which are adverse prognostic markers among patients treated with chemoimmunotherapy.

The Bruton tyrosine kinase (BTK) inhibitor ibrutinib is approved for patients with untreated, relapsed, or refractory disease, including those with del(17p). Clinicians will soon have the chance to pair it with ublituximab, a next-generation, glycoengineered, type I, anti-CD20 monoclonal antibody that binds to a unique epitope on CD20, differentiating it from rituximab, ofatumumab, and obinutuzumab. Results from the phase 3 GENUINE trial, which were recently published in The Lancet Haematology, showed that ublituximab plus ibrutinib was superior to ibrutinib alone for patients with relapsed or refractory high-risk CLL.

Source: Medscape

Quadruple therapy with an angiotensin receptor–neprilsyin inhibitor (ARNI), evidence-based β-blocker, mineralocorticoid receptor antagonist (MRA), and sodium glucose cotransporter 2 inhibitor (SGLT2i) may reduce risk of death by 73% over 2 years in patients with heart failure (HF) with reduced ejection fraction (HFrEF).

Simultaneous or Rapid Sequence Initiation of Comprehensive Disease-Modifying Medical Therapy (CDMMT) for Heart Failure:

Source: JAMA

European Union approval has been recommended for duvelisib (Copiktra) for patients with relapsed/refractory chronic lymphocytic leukemia (CLL) or refractory follicular lymphoma (FL) who have received at least two prior lines of therapy.

Duvelisib is an inhibitor of phosphoinositide 3–kinase (PI3K) and is the first drug to act as a dual inhibitor of PI3K-delta and PI3K-gamma. These enzymes are involved in the proliferation and survival of malignant B-cell lines and primary CLL tumor cells and are involved in immunologic pathways in the tumor microenvironment of malignant B cells.

Duvelisib is already on the market in the United States; it was approved in 2018 for the same two indications and also for use in the treatment of small lymphocytic lymphoma (CLL/SLL).

The US FDA has approved dasiglucagon (Zegalogue 0.6 mg/0.6 mL, Zealand Pharma) autoinjector and prefilled syringe for the treatment of severe hypoglycemia in people with diabetes aged 6 and older.

The product has a shelf-life of 36 months at refrigerated temperatures and is stable for up to 12 months at room temperature.

Dasiglucagon is currently in phase 3 trials as a SC infusion for treating congenital hyperinsulinemia, and in phase 2 trials as part of a bihormonal artificial pancreas pump system.

The FDA approval was based on results from three randomized, double-blind, placebo-controlled phase 3 studies of dasiglucagon in children age 6 to 17 years and adults with type 1 diabetes.

The primary endpoint was time to achieving an increase in blood glucose of 20 mg/dL or greater from time of administration without additional intervention within 45 minutes. That endpoint was achieved in all three studies, with a median time to blood glucose recovery of 10 minutes overall, with 99% of adults recovering within 15 minutes.

The most common adverse events reported in 2% or more of study participants were nausea, vomiting, headache, and injection site pain in both children and adults. Diarrhea was also reported in adults.

Full launch is expected in late June 2021.

Source: FDA

The US FDA has approved a new, once-daily oral stimulant medication for the treatment of attention deficit hyperactivity disorder (ADHD) in people aged 6 years and older.

Azstarys (KemPharm, Inc) combines serdexmethylphenidate (SDX) + dexmethylphenidate (d-MPH), coformulated with immediate-release d-MPH.

Dosage: Azstarys will be available in three once-daily dosage strengths of SDX/d-MPH: 26.1 / 5.2 mg, 39.2 / 7.8 mg, and 52.3 / 10.4 mg.

Adverse effects: headache, upper abdominal pain, insomnia and pharyngitis.

Pharmacology: Following absorption in the gastrointestinal tract, SDX is converted to d-MPH, which is gradually released throughout the day, providing symptom control both rapidly with the d-MPH and for an extended duration with SDX.

Study: The study included 150 children aged 6 to 12 years with ADHD. Compared with placebo, treatment with Azstarys led to significant improvement in ADHD symptoms, as measured by the primary endpoint, the change from baseline in Swanson, Kotkin, Agler, M-Flynn, and Pelham Rating Scale – Combined (SKAMP-C) scores averaged over 13 hours.

The FDA has recommended a schedule II controlled substance classification for Azstarys.

Source: FDA

The U.S. Food and Drug Administration granted approval for Amondys 45 (casimersen) injection for the treatment of Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 45 skipping (Exons are pieces of DNA that provide information for making proteins in a person’s genome). The agency approved Amondys 45 based on an increase in dystrophin (a protein that helps keep muscle cells intact) production in skeletal muscle observed in patients treated with the therapy. This is the first FDA-approved targeted treatment for patients with this type of mutation. Approximately 8% of patients with DMD have a mutation that is amenable to exon 45 skipping.

Dose: 30 mg/kg IV

Side effects:  Upper respiratory tract infections, cough, fever, headache, joint pain and throat pain.

Source: FDA

The US FDA has approved the fully human monoclonal antibody evinacumab-dgnb (Evkeeza, Regeneron Pharmaceuticals) for use on top of other cholesterol-modifying meds in patients aged 12 and older with homozygous familial hypercholesterolemia (HoFH).

Mechanism: Evinacumab-dgnb is a fully-human monoclonal antibody that binds to and blocks the function of ANGPTL3.

Dose: 15 mg/kg) once a month via intravenous infusion.

Adverse Effects: Nasopharyngitis, influenza-like illness, dizziness, rhinorrhea, nausea, pain in extremity and asthenia.

Cost: $450,000 per year

Extra notes: Reductions in LDL-C seen were observed as early as week 2 and maintained throughout the double-blind treatment period (week 24) and open-label trial period (through week 48).

FDA approves Sogroya (somapacitan-beco) a 0nce-weekly treatment for Adult Growth Hormone Deficiency.

Sogroya (somapacitan-beco) injection 10 mg/1.5 mL (6.7 mg/mL) is a human growth hormone analog taken once a week by subcutaneous injection. The FDA’s decision is based on a comprehensive clinical program, including the REAL 1 study, a 35-week, double-blind, placebo-controlled study, in treatment-naïve adult patients with GHD.

Sogroya may cause serious side effects, including:

• High risk of death in people who have critical illnesses because of heart or stomach surgery, trauma or serious breathing problems
• Increased risk of growth of cancer or a tumor that is already present and increased risk of the return of cancer
• New or worsening high blood sugar or diabetes
• Odema
• Decrease in a hormone called cortisol
• Decrease in thyroid hormone levels.
• Severe and constant abdominal pain. This could be a sign of pancreatitis
• Loss of fat and tissue weakness in the area of skin you inject.
• Increase in phosphorus, alkaline phosphatase and parathyroid hormone levels in your blood

The most common side effects of Sogroya may include back pain, joint pain, indigestion, sleep problems, dizziness, swelling of the tonsils, vomiting, high blood  pressure, increase creatine phosphokinase, weight gain, and low red blood cells

Source: FDA

The FDA has approved collagenase clostridium histolyticum for the treatment of moderate to severe cellulite in the buttocks of adult women. The drug is the first injectable treatment for cellulite to receive regulatory approval.

Dose: 0.9mg Solution, Injection

MOA: When injected into the treatment area, It is thought to release the fibrous septae enzymatically by specifically targeting types 1 and 3 collagen, which may result in the smoothing of the skin and an improved appearance of cellulite.

Common side effects: Injection site bruising, pain, areas of hardness, itching, redness, discoloration, swelling, and warmth in the treatment area.

In cellulite, fibrous septae are a primary contributing factor. The septae make up the fibrous connective tissue that connects the skin perpendicularly to the fascia below and tether the skin, drawing it downward and leading to a mattress-like appearance, commonly referred to as “dimpling.”

The US Food and Drug Administration (FDA) has approved Tecentriq® (atezolizumab) in combination with Avastin® (bevacizumab) for the treatment of people with unresectable or metastatic hepatocellular carcinoma (HCC) who have not received prior systemic therapy.

Atezolizumab is a monoclonal antibody designed to bind with a protein called PD-L1, which is expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, it may enable the activation of T-cells.

Bevacizumab is a biologic antibody designed to specifically bind to a protein called VEGF that plays an important role throughout the lifecycle of the tumour to develop and maintain blood vessels, a process known as angiogenesis. It is designed to interfere with the tumour blood supply by directly binding to the VEGF protein to prevent interactions with receptors on blood vessel cells. The tumour blood supply is thought to be critical to a tumour’s ability to grow and spread in the body (metastasis).

Source: Roche, fda.gov