ACCRUFER™ (ferric maltol)
Shield Therapeutics received FDA approval for their lead product Accrufer™ (ferric maltol) for the treatment of iron deficiency in adults with or without anemia, allowing use for as long as necessary to restore iron levels. Unlike other iron supplements, Accrufer™ is not an iron salt, which allows it to be absorbed from the ferric maltol molecule allowing long-term use in patients with chronic disease. Accrufer™ 30 mg is supplied in bottles of 56 capsules.
AirDuo Digihaler™ (fluticasone propionate and salmeterol) Inhalation Powder
Expected to be available in 2020, AirDuo Digihaler™ (Teva Pharmaceuticals) is a combination of fluticasone propionate, a corticosteroid, and salmeterol, a long-acting beta2-adrenergic agonist (LABA) and is indicated for the treatment of asthma in patients aged 12 years and older. AirDuo Digihaler™ has a built-in electronic module which detects, records, and stores data on inhaler events for transmission to a mobile application (using Bluetooth Wireless technology).
BAQSIMI™ (glucagon) nasal powder
Eli Lilly’s Baqsimi™ is the first and only nasally administered glucagon to treat severe hypoglycemia in adults and children with diabetes ages four years and older. Baqsimi™ is compact, portable and ready to use (no priming required) and available in a single, fixed, 3 mg dose. Side effects are similar to the injectable glucagon, with the addition of nasal and eye-related symptoms because of the way the drug is administered.
Descovy – FDA approves second drug to prevent HIV infection as part of ongoing efforts to end the HIV epidemic
The FDA approved Descovy® (emtricitabine 200 mg and tenofovir alafenamide 25 mg) in at-risk adults and adolescents weighing at least 35kg for HIV-1 pre-exposure prophylaxis (PrEP) to reduce the risk of HIV-1 infection from sex, excluding those who have receptive vaginal sex. Descovy® is not indicated in individuals at risk of HIV-1 infection from receptive vaginal sex because the effectiveness in this population has not been evaluated. This makes Descovy® the second drug approved by the FDA to be used as PrEP, following the approval of Truvada (also manufactured by Gilead) in 2012. Previously, Descovy® was approved in combination with other antiretroviral drugs to treat HIV-1 infection in adults and pediatric patients.
The approval was based on data from the phase 3 DISCOVER trial that found Descovy® to be noninferior to Truvada® for PrEP in reducing the risk of HIV-1 infection in at-risk men and transgender women. In addition, the study showed statistically significant improvements in renal and bone laboratory parameters in patients receiving Descovy® compared with those on Truvada®. The approval of Descovy® for PrEP may drive some current utilizers of Truvada® to Descovy®. In addition, Truvada® is expected to become available as generic in September 2020. The release of generic Truvada® may again impact the utilization for PrEP.
Ga 68 Dotatoc Injection
The FDA approved Ga 68 Dotatoc Injection as a radioactive diagnostic agent indicated for use with positron emission tomography (PET) for localization of somatostatin receptor positive neuroendocrine tumors (NETs) in adult and pediatric patients. Ga 68 Dotatoc Injection is supplied in a multiple-dose glass vial containing 18.5 MBq/mL to 148 MBq/mL (0.5 mCi/mL to 4 mCi/mL).
The FDA approved Ibsrela® (tenapanor) 50 mg, twice daily orally tablet for the treatment of irritable bowel syndrome with constipation (IBS-C) in adults. Ibsrela® is a minimally-absorbed small molecule that acts locally in the gastrointestinal (GI) tract to inhibit the sodium-hydrogen exchanger NHE3 resulting in an increase in bowel movements and a decrease in abdominal pain for IBS-C patients.
The FDA approved Inrebic® (fedratinib) capsules to treat adult patients with intermediate-2 or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis. The recommended dosage is 400 mg orally once daily with or without food for patients with a baseline platelet count of greater than or equal to 50 x 109/L. Inrebic® carries a box warning about the risk of serious and fatal encephalopathy (brain damage or malfunction).
Jynneos™ Smallpox and Monkeypox Vaccine
The FDA approved Jynneos™ Smallpox and Monkeypox Vaccine, Live, Non-Replicating, for the prevention of smallpox and monkeypox disease in adults 18 years of age and older determined to be at high risk for smallpox or monkeypox infection. This is the only currently FDA-approved vaccine for the prevention of monkeypox disease. The vaccine will be made available for clinically determined high-risk patients, and will also be included in the Strategic National Stockpile, the US’ greatest surplus of pharmaceuticals and medical supplies for us in potentially severe public health emergencies. Jynneos™ is a suspension for subcutaneous injection (0.5 mL) based on a live, attenuated vaccinia virus (Modified Vaccinia Ankara, MVA-BN).
MYXREDLIN™ (insulin human in sodium chloride) injection
Baxter International announced the FDA approval of Myxredlin™, the first and only ready-to-use insulin for IV infusion. Myxredlin™ is a short-acting human insulin to improve glycemic control in adults and pediatric patients with diabetes mellitus and is intended for use only in acute care settings under medical supervision. It is available in a single-dose container of 100 units insulin human in 100 mL of 0.9% sodium chloride (1 unit/mL) with a shelf life of 30 days at room temperature or 24 months refrigerated in original container.
The FDA approved Nourianz™ (istradefylline) tablets as an add-on treatment to levodopa/carbidopa in adult patients with Parkinson’s disease (PD) experiencing “off” episodes. Nourianz is an oral selective adenosine A2A receptor antagonist and non-dopaminergic pharmacologic option. Nourianz™ is supplied in 20 mg, and 40 mg tablets.
The FDA approved Nubeqa® (darolutamide), an androgen receptor inhibitor, for the treatment of patients with nonmetastatic castration resistant prostate cancer (nmCRPC). The recommended dose for Nubeqa is 600mg (two tablets) twice a day. A gonadotropin-releasing hormone (GnRH) analog, such as leuprolide, also should be used for patients who have not had a bilateral orchiectomy (surgical castration). Bayer has not yet announced a launch date.
The FDA approved of pretomanid tablets in combination with bedaquiline and linezolid for the treatment of adults with pulmonary extensively drug resistant (XDR), treatment-intolerant or nonresponsive multidrug-resistant (MDR) tuberculosis (TB). Pretomanid is an oral nitroimidazooxazine antimycobacterial that works by killing actively replicating M. tuberculosis by inhibiting mycolic acid biosynthesis, thereby blocking cell wall production. Pretomanid is the second drug to be approved under the Limited Population Pathway for Antibacterial and Antifungal Drugs, or LPAD pathway. Pretomanid is expected to be available in the US by the end of this year.
Recarbrio™ (imipenem, cilastatin and relebactam)
The FDA announced the approval of Recarbrio™ (imipenem, cilastatin and relebactam) 1.25 gram injection, an antibacterial drug used to treat patients 18 years of age or older with complicated urinary tract infections (cUTI) and complicated intra-abdominal infections (cIAI). Merck anticipates making Recarbrio™ available later in 2019.
The FDA approved Rinvoq™ (upadacitinib), a Janus kinase (JAK) inhibitor, for the treatment of adults with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to methotrexate. This is the third JAK inhibitor approved for RA. The other two are Xeljanz® and Olumiant®. Rinvoq™ is supplied as 15mg extended-release tablets.
Genentech announced the FDA approved Rozlytrek™ (entrectinib) for the treatment of adults with ROS1-positive, metastatic non-small cell lung cancer (NSCLC). The FDA also approved it for the treatment of adult and pediatric patients 12 years of age and older with solid tumors that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have progressed following treatment or have no satisfactory alternative therapy. This marks the third approval of a tissue-agnostic cancer therapy indicated for treatment across cancer types based on the presence of a specific biomarker. Previous tissue-agnostic indications approved by the FDA included pembrolizumab (Keytruda®) for tumors with microsatellite instability-high or mismatch repair deficient tumors and larotrectinib (Vitrakvi®) for NTRK gene fusion tumors.
The FDA approved Rybelsus® (semaglutide) oral tablets to improve control of blood sugar in adult patients with type 2 diabetes, along with diet and exercise. Rybelsus® is the first glucagon-like peptide (GLP-1) receptor protein treatment approved for use in the United States that does not need to be injected. GLP-1 drugs are non-insulin treatments for people with type 2 diabetes. The drug carries a box warning about the potential increased risk of thyroid c-cell tumors, and it is not recommended as the first choice of medicine for treating diabetes. Rybelsus® should be taken at least 30 minutes before the first food, beverage or other oral medication of the day, with no more than 4 ounces of plain water. Rybelsus® slows digestion, so patients should discuss other medications they are taking with their health care provider before starting Rybelsus®. Rybelsus® is available as 3 mg, 7 mg or 14 mg tablets.
The FDA approved Turalio™ (pexidartinib) capsules for the treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT) – rare type of disease associated with severe morbidity or functional limitations and not responsive to improvement with surgery. This is the first FDA-approved treatment for this rare disease. Turalio™ carries a box warning flagging the risk of serious and potentially fatal liver injury.
The FDA approved Wakix® (pitolisant) as the first treatment for patients with narcolepsy that is not scheduled as a controlled substance by the US Drug Enforcement Administration (DEA). Wakix® is a selective histamine 3 (H₃) receptor antagonist/inverse agonist that works through a mechanism of action to increase the synthesis and release of histamine, a wake-promoting neurotransmitter in the brain. Wakix® is administered orally once daily in the morning upon wakening, it is supplied in 4.45 mg and 17.8 mg tablets. Harmnony Biosciences’ Wakix® will be commercially available in the fourth quarter of 2019.
The FDA approved Xenleta™ (lefamulin) for the treatment of adults with community-acquired bacterial pneumonia (CABP). Xenleta™ is a first-in-class semisynthetic pleuromutilin antibiotic targeted most common causative gram-positive, gram-negative, and atypical pathogens associated with CABP. Xenleta™ will be supplied as 600mg tablets and as a 150mg/15mL single-dose vial intended for dilution in 250mL of 10mM citrate buffered (pH 5) 0.9% sodium chloride; the diluent is provided in infusion bags.
ADDITIONAL CLINICAL BULLETIN
Alnylam’s Givosiran Gets FDA Priority Review for Acute Hepatic Porphyria
The FDA granted priority review for givosiran (Alnylam) for the treatment of acute hepatic porphyria (AHP). AHP is a rare, genetic disease characterized by episodic and potentially life-threatening attacks. Givosiran is a subcutaneously administered RNAi therapeutic targeting aminolevulinic acid synthase 1 (ALAS1); treatment is expected to lower induced liver ALAS1 levels and decrease these intermediates. Givosiran was previously granted Breakthrough Therapy designation and Orphan Drug designation from the FDA. The safety and efficacy of givosiran were evaluated in the ENVISION Phase 3 trial with positive results; these results have not been evaluated by the FDA, the EMA or any other health authority. A Prescription Drug User Fee Act (PDUFA) action date for the NDA has been set for February 4, 2020.
Fast Track Status Granted to Ecopipam for the Treatment of Tourette Syndrome
A potential first-in-class therapy ecopipam has received Fast Track designation for the treatment of Tourette Syndrome (TS). Tourette Syndrome (TS) is a neurological disorder characterized by motor or vocal tics. Ecopipam works by selectively blocking the actions of the D1 receptor. This mechanism may potentially reduce the likelihood of metabolic and movement disorders that have been previously linked to D2 antagonist therapy, while still treating the repetitive and compulsive behaviors associated with the disorder. Ecopipam is currently being evaluated in the phase 2 D1AMOND study in children and adolescents with TS. Ecopipam has been shown to be generally well tolerated in clinical trials conducted to date, including in adult and pediatric patients with TS.
Zilucoplan Gets Orphan Drug Designation for Myasthenia Gravis Treatment
The FDA has granted Orphan Drug designation to zilucoplan for the treatment of generalized myasthenia gravis (gMG) and other rare, tissue-based complement-mediated diseases. Zilucoplan is an investigational, synthetic, macrocyclic peptide inhibitor of complement component 5 (C5) that binds to and inhibits the cleavage of C5 into C5a and C5b preventing 3 pathways of complement activation. The product is easy to use, self-administered subcutaneous treatment option to address the underlying cause of gMG through targeted complement control. The designation is supported by data from a 12-week, randomized, double-blind, placebo-controlled, phase 2 clinical trial that evaluated the efficacy and safety of zilucoplan in adult patients with gMG. The primary end point of the study was change from baseline in Quantitative Myasthenia Gravis (QMG) score; change from baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) scale was a secondary outcome measure.
PR001 Gets Fast Track Status for Parkinson Disease with GBA1 Mutation
The FDA has granted Fast Track designation to PR001 for the treatment of Parkinson disease patients with a GBA1 mutation (PD-GBA). PR001 is a potentially disease-modifying, single-dose, AAV9-based gene therapy being developed for the treatment of PD-GBA and neuronopathic Gaucher disease. Parkinson disease with a GBA1 mutation (PD-GBA) is a chronic and progressive neurodegenerative disorder that comprises 7% to 10% of the total Parkinson disease population in the world. A phase 1/2 clinical trial is planned in the second half of 2019 to investigate the safety and tolerability of PR001, key biomarkers, and exploratory efficacy endpoints in patients with PD-GBA.
The “Pipeline Update: NASH – Boom or Bust?”
Nonalcoholic fatty liver disease (NAFLD) is a widespread, largely asymptomatic condition that results from fat accumulation in the liver. It ranges in severity from essentially harmless simple steatosis (simple fatty liver) to a progressive form, nonalcoholic steatohepatitis (NASH), which damages liver cells and causes inflammation. NASH can lead to serious liver conditions that include death due to liver failure. Less common than simple steatosis, NASH still is estimated to affect as many as 16 million Americans, including children and teens. However, an invasive diagnostic procedure, limited current treatment options and the delayed availability of outcomes data with pipeline therapies may hinder the uptake of therapies approved to treat NASH, at least initially. This Issues Document summarizes our current thoughts surrounding drugs to treat NAFLD/NASH, a potential blockbuster therapy class. Details attached in document link: NASH Update Document
FDA Reviewing Manipulated Data from Zolgensma® SMA Application
The US Food and Drug Administration (FDA) is currently assessing the manipulation of data which accompanied applications of spinal muscular atrophy (SMA) gene therapy abeparvovec (Zolgensma®)—a drug which the FDA had approved for children aged 2 years or younger with SMA in late May. According to a statement from the FDA on Tuesday, the agency was informed of a data manipulation issue affecting the accuracy of the product’s performance in animal models as part of its Biologics License Application (BLA) submitted to and reviewed by the FDA prior to the marketing decision. Novartis submitted a drug application with manipulated data and did not inform regulators of the issue until one month after approval. The company was aware of the issues two months before the FDA greenlighted the drug. Still, the FDA believes the drug should remain on the market. The drug now carries the world’s highest pharma price tag at $2.125 million and treats certain SMA patients under two.