Monthly News Roundup – September 2020

Genentech’s Gavreto Cleared for RET Fusion-Positive NSCLC

Gavreto (pralsetinib) is a RET kinase inhibitor used for the treatment of adults with metastatic rearranged during transfection (RET) fusion positive non-small cell lung cancer (NSCLC), as detected by an FDA approved test. Patients with RET gene alterations have limited treatment options.

  • FDA approved Gavreto under accelerated approval. In the Phase I/II ARROW study, Gavreto demonstrated an overall response rate (ORR) of 57% in the group with NSCLC previously treated with platinum-based chemotherapy and 70% in a treatment-naïve group.
  • The Gavreto dose is 400 mg orally once daily on an empty stomach.
  • Commonly reported side effects (≥25%) were fatigue, constipation, musculoskeletal pain and increased blood pressure (hypertension).

Bristol Myers Squibb’s Onureg Approved for Acute Myeloid Leukemia 

Onureg (azacitidine) is a nucleoside metabolic inhibitor indicated for the continued treatment of adult patients with acute myeloid leukemia (AML). AML, a cancer of white blood cells, starts inside the bone marrow. AML leads to frequent infections, anemia, bruising and bleeding.

  • Onureg is used in patients who had a first complete remission following intensive induction chemotherapy with or without recovery of blood cell counts; and in those who are not able to complete intensive curative therapy.
  • Approval is based on data from the Phase III QUAZAR AML-001 study. Median overall survival, the primary endpoint, was greater than two years (24.7 months) in the Onureg arm compared to 14.8 months for the placebo group, a statistically significant result.
  • The most common side effects with Onureg were nausea, vomiting, diarrhea, fatigue/asthenia, and constipation, among others.

FDA Approves Qdolo Oral Solution for Severe Pain

Qdolo (tramadol hydrochloride) from Athena Bioscience is a C-IV opioid agonist oral solution approved for adults to manage pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.

  • Qdolo is available as a 5 mg/mL oral solution to allow flexible dosing and titration as directed in labeling. Do not administer Qdolo at a dose exceeding 400 mg (80 mL) per day.
  • Qdolo contains a Boxed Warning, the FDA’s most stringent warning, advising on multiple opioid safety concerns, including addiction, abuse, ultra-rapid metabolism, overdose, respiratory depression and death.
  • Do not use Qdolo in children younger than 12 years of age. In addition, do not use Qdolo in children younger than 18 years of age for postoperative management after a tonsillectomy and/or adenoidectomy.
  • Common side effects are dizziness/vertigo, nausea, constipation, headache, somnolence, vomiting and pruritus (itching).

Trulicity: Two Higher Doses OK’d for Type 2 Diabetes

Eli Lilly’s Trulicity (dulaglutide) is an injectable glucagon-like peptide-1 (GLP-1) receptor agonist used for the treatment of type 2 diabetes. Diabetes is a long-term disease that occurs when the body does not properly produce or use insulin.

  • The approval expands the label of once-weekly Trulicity single-dose pens to include 3 mg and 4.5 mg doses based on data from the 36 week AWARD-11 study. The new doses are expected to be available by the end of September.
  • Significant reductions in A1C and body weight occurred when compared to Trulicity 1.5 mg, in patients also on metformin: 4.5 mg dose (A1C: -1.9%, weight: -10.4 lb); 3 mg dose (A1C: -1.7%; weight: -8.8 lb). 1.5 mg dose (A1C: -1.5%; weight: -6.8 lb).
  • Common side effects with Trulicity include: nausea, diarrhea, vomiting, abdominal pain, and decreased appetite.

GSK’s Trelegy Ellipta Inhaler Gains New Use for Asthma Maintenance 

In September, Trelegy Ellipta (fluticasone furoate, umeclidinium and vilanterol) gained a new indication for the once-daily treatment of asthma in adults. Trelegy Ellipta was also previously approved for chronic obstructive pulmonary disease (COPD).

  • Trelegy Ellipta combines an inhaled corticosteroid (ICS), a long-acting beta-agonist (LABA), and an inhaled anticholinergic in a single inhaler, and can boost bronchodilation compared to a ICS/LABA used alone.
  • Approval was based on the Phase III CAPTAIN study which compared Trelegy Ellipta to Breo (fluticasone furoate and vilanterol), both given once daily. A significant improvement in trough FEV1 from baseline (the primary endpoint) was demonstrated at week 24 for Trelegy.
  • Common side effects included common cold symptoms, headache, upper respiratory tract infection, and bronchitis.

Pfizer’s Oral Xeljanz Cleared for Juvenile Idiopathic Arthritis

This past month, the FDA approved Xeljanz (tofacitinib), an oral Janus kinase (JAK) inhibitor for polyarticular course juvenile idiopathic arthritis (pcJIA) in children 2 years and older. This approval makes Xeljanz the only JAK approved in the US for the treatment of pcJIA.

  • Two formulations were approved in children, a tablet and an oral solution (1 mg/mL), with both dosed on weight. Oral formulations may enhance pediatric acceptance over injections.
  • Study results show that disease flare in patients treated with tofacitinib (31%) was significantly lower than patients treated with placebo (55%) at week 44. Side effects were similar to those seen in adult rheumatoid arthritis.
  • In adults, Xeljanz is also approved for the treatment of rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis.

FDA Approves Nucala as the First Biologic for Hypereosinophilic Syndrome (HES)

This past month, the FDA approved GSK’s Nucala (mepolizumab) for the treatment of patients aged 12 years and older with Hypereosinophilic Syndrome (HES) for at least six months without an identifiable non-hematologic secondary cause. Nucala is classified as an IL-5 antagonist.

  • HES is a rare, life-threatening disease marked by overproduction of eosinophils, a type of white blood cell. Patients may exhibit fever, discomfort, and breathing and heart problems.
  • When compared to placebo, 50% fewer patients (28% vs 56%) experienced a flare when treated with Nucala added to standard of care over the 32-week study period, a significant effect.
  • For HES, the recommended Nucala dose is 300 mg as 3 separate 100-mg injections administered subcutaneously once every 4 weeks. 
  • Common side effects include: headache, injection site reaction, back pain, and fatigue.

Haegarda Use Expanded for Hereditary Angioedema Prevention in Younger Age Group

CSL Behring announced approval for Haegarda (C1 esterase inhibitor [human]) as routine prophylaxis to prevent hereditary angioedema (HAE) attacks in patients 6 years of age and older. Patients or caregivers can be taught to self-inject the subcutaneous formulation.

  • Previously, Haegarda was approved for patients 12 years of age and older and is now the only subcutaneous option for patients 6 years and older.
  •   HAE is a rare, genetic condition leading to painful episodes of swelling throughout the body. HAE is caused by deficient or altered C1-INH, a protein that controls swelling. 
  • In COMPACT OLE (n=126), patients received 40 IU/kg or 60 IU/kg C1-INH(SC) twice per week (with dose adjustments if needed). All 9 pediatric patients (3 patients aged <12 y) experienced greater than 50% reduction in number of attacks per month. All patients had less than one attack per 4-week period and 4 patients had less than one attack per year.
  • The most commonly reported side effect in COMPACT OLE was mild injection-site reactions.

Posted: September 2020

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