FDA Update: April 2018

Apr 11, 2018
Express Scripts Office of Clinical Evaluation and Policy tracks some recent updates to the drug pipeline.

New Pill Bottle

Over the past month, the Express Scripts Emerging Therapeutics team followed U.S. Food and Drug Administration actions that resulted in some new drug approvals, several new generics, a few additional indications and one market withdrawal:

Apadaz Approved to Treat Acute Pain

KemPharm’s Apadaz™ (benzhydrocodone/acetaminophen) tablets was approved by the FDA on Feb. 23, 2018. It is an immediate-release opioid/acetaminophen combination product indicated for treating intense, acute pain that has not responded to other therapies. The recommended dose is one or two tablets every four to six hours as needed. No more than 12 tablets should be taken in any 24-hour period and treatment should last no longer than two weeks. The benzhydrocodone component is a prodrug that is not activated until it is exposed to gastrointestinal (GI) enzymes. Crushing it to inhale, inject or smoke will not produce the euphoria associated with misuse of other immediate-release opioids. However, it still can be misused by swallowing. Therefore, the FDA does not consider it to be abuse deterrent and it cannot claim to be in its labeling. The U.S. Drug Enforcement Administration (DEA) will schedule Apadaz as a C-II controlled substance, meaning that it has a high possibility for abuse. All opioids, including Apadaz, have several boxed warnings, including risks for abuse, addiction, overdose and respiratory depression. They caution about neonatal withdrawal syndrome for babies born to women who used opioids while pregnant, as well. Apadaz will be dispensed with a Medication Guide and under a Risk Evaluation and Mitigation Strategy (REMS). Although KemPharm has not yet announced its launch or pricing plans, it has indicated that it is open to innovative distribution arrangements. The cost of Apadaz is expected to be close to those of comparable generics. It will be evaluated for the “Exclude at Launch” Program of the National Preferred Formulary (NPF). For full prescribing information, click here.

FDA Approval for ZTlido

Sorrento Therapeutics announced on Feb. 28, 2018, that its subsidiary, Scilex Pharmaceuticals has received FDA approval for ZTlido™ (lidocaine topical system) 1.8%. It is indicated to treat post-herpetic neuralgia (PHN), which is pain that continues after a case of shingles. Because it uses a different type of patch design, ZTlido is bioequivalent to currently available lidocaine patches, such as Lidoderm® (lidocaine) Patch 5%. It has a unique adhesive, as well, which provides more consistent skin contact. Some clinical trial patients developed mild, temporary blistering, burning, irritation, itching, redness, swelling or other topical side effects where it was applied, however. A launch is expected before the end of 2018, but prescribing and pricing information have not been released.

Zinbryta Worldwide Market Withdrawal

On March 2, 2018, AbbVie and Biogen announced the voluntary withdrawal of Zinbryta® (daclizumab) from the worldwide market. Zinbryta, an interleukin-2 receptor blocking antibody, was launched on the U.S. market in 2016 for the treatment of relapsing forms of multiple sclerosis. The decision to discontinue marketing was made following reports of brain inflammation, known as inflammatory encephalitis and meningoencephalitis, in patients taking the drug. Although a removal timeline has not been established, Biogen and AbbVie will work collaboratively with the FDA and healthcare providers in the management of Zinbryta patients. According to Biogen, patients with questions or concerns should contact their healthcare providers.

Trogarzo Approved for HIV

Theratechnologies and TaiMed Biologics received approval from the FDA on Mar. 6, 2018, for Trogarzo™ (ibalizumab-uiyk) for use in combination with other antiretroviral therapies. It is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in heavily treatment-experienced adults with multidrug resistant HIV-1 infection failing their current antiretroviral regimen. Trogarzo is administered in intravenous (IV) infusions as a single loading dose of 2,000mg followed by a maintenance dose of 800mg once every two weeks. Theratechnologies plans to launch Trogarzo within six weeks of its approval through a limited network of specialty pharmacies that includes Accredo. Full prescribing information will be available here.

Generics to Sensipar Approved; Launch Pending

On March 8, 2018, the FDA approved the first AB-rated generics to Amgen’s Sensipar® (cinacalcet), a drug for the treatment of secondary hyperparathyroidism (HPT) in adult patients who have chronic kidney disease and who are on dialysis. It also is approved to treat high calcium levels (hypercalcemia) in patients with parathyroid carcinoma, and those who have primary HPT but are unable to undergo parathyroidectomy. According to the FDA’s website, both Aurobindo and Cipla have received approval for generics to the 30mg, 60mg and 90mg tablets. However, due to recent patent settlement agreements, launch plans are not known. Annual sales for Sensipar are approximately $1.7 billion, according to IQVIA (formerly QuintilesIMS).

Generic Launched for Norvir Tablets

The West-Ward Pharmaceuticals subsidiary of Hikma Pharmaceuticals introduced the first AB-rated generic for Norvir® (ritonavir) tablets on March 20, 2018. Ritonavir is a protease inhibitor used in combination with other antiretroviral agents to treat HIV-1 for patients as young as one month old. Recommended dosing for adult patients who are not taking an additional protease inhibitor is 600mg (six tablets) twice a day. However, ritonavir is used more commonly and at lower doses as a booster for other drugs in the same class. West-Ward, which has 180-days of generic exclusivity in the U.S., intends to offer patient assistance and copayment programs along with Internet and written educational materials. Labeling for ritonavir carries a boxed warning that using it with one of several other drugs, including some treatments for angina, cardiac arrhythmias, migraines or psychoses, could result in severe side effects. No generics are available yet for Norvir capsules or oral solution. IQVIA estimates that 2017 sales of all strengths and dose forms of Norvir amounted to nearly $214 million in the U.S.

Ilumya Approved for Plaque Psoriasis

Sun Pharma announced on Mar. 21, 2018, that the FDA had approved Ilumya™ (tildrakizumab-asmn) for the treatment of adults who have moderate-to-severe plaque psoriasis and who are candidates for systemic therapy or phototherapy. Ilumya is a biologic drug known as an interleukin-23 (IL-23) inhibitor. The recommended dose is 100mg by subcutaneous (SC) injection at Weeks 0 and 4, and then every 12 weeks thereafter. Sun Pharma plans on launching Ilumya in late June or early July. It will be available through a large network of specialty pharmacies that includes Accredo. Full prescribing information can be found here.

New Pediatric Indications for Tasigna

The FDA gave approval to Novartis’ tyrosine kinase inhibitor (TKI), Tasigna® (nilotinib) on March 22, 2018, for treating children and teens who are in chronic phase Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). According to the National CML Society, only about 3% of pediatric leukemia patients have CML. Tasigna can be used for children at least one year old who are new to treatment, as well as for those who already have had TKI therapy that did not work or that caused unbearable side effects. Tasigna is taken orally at recommended pediatric doses of 230mg/m2 twice a day, up to a maximum of 400mg per dose. It must be taken two hours before or one hour after eating. Its label has a boxed warning that taking it has been associated with disturbances in heart rhythm and that some affected patients have died as a result. Full prescribing information can be accessed here.

Generics launched for Aloxi 0.25mg/5mL

Immediately after it received FDA approval on March 23, 2018, Teva Pharmaceutical Industries, Inc. launched its generic for Eisai/Helsinn’s Aloxi® (palonosetron) injection for intravenous use, 0.25mg/5mL. One authorized generic and other generics have also been introduced – at least one under a settlement agreement. However, the brand co-manufacturers are considering further legal action after their patents were invalidated by a U.S. federal appeals court. Palonosetron is a 5-HT3 receptor antagonist used to prevent nausea and vomiting associated with cancer chemotherapy (chemo) and for patients undergoing surgery. It is approved for patients as young as one month old. For children and teens up to 18 years old, doses are calculated by weight. The recommended adult dose is 0.25mg through a 30-second IV infusion about one-half hour before chemo starts. A much lower dose, 0.075mg, is given right before anesthesia for patients having surgery. Single-dose vials containing 0.075mg/1.5mL remain brand-only. According to IQVIA, global sales for Aloxi 0.25mg/5mL were around $452 million during 2017.

Toujeo Max SoloStar Approved

A larger pre-filled pen device for Toujeo® (insulin glargine 300 Units/mL) was approved by the FDA on March 26, 2018. Called the Toujeo Max SoloStar®, it holds 3mL (900 units), which is twice the amount in the previously available device. Toujeo is injected SC once a day to control diabetes for adults who have either type 1 or type 2. Individual doses of Toujeo can be as high as 160 Units through the Max device, as opposed to 80 Units previously. Sanofi plans to introduce the larger pens in the third quarter of 2018 at the same cost as the original, smaller one. Prescribing information can be found here.

Blincyto Gains New Indication

Using its accelerated approval process, the FDA gave Blincyto® (blinatumomab) a new leukemia indication on March 29, 2018. A bispecific CD19-directed CD3 T-cell engager, Blincyto was first FDA approved in 2014 for treating adults who have Philadelphia chromosome-negative (Ph-) B-cell precursor acute lymphoblastic leukemia (ALL) that has recurred or that is no longer responding to previous treatment. Later, a pediatric indication for the same cancer also was added. Now, it is the first drug approved for treating children and adults who are in remission for the same type of ALL, but who still have cancer cells that cannot be detected through a microscope. Called minimal residual disease (MRD), even such low levels (0.1% or more) of cancer significantly raise the chance of a relapse. For MDR-ALL, Blincyto is given for one 42-day induction cycle, followed by up to three 42-day consolidation cycles. Dosing for adults is 28mcg/day of active treatment (28 continuous days) then 14 drug-free days. Doses for patients weighing less than 45 Kg (99 pounds) are determined by the patient’s body surface area. Blincyto is administered through a continuous IV pump in a healthcare facility. Patients should be hospitalized for at least the first three days of their first treatment cycle, and for the first two days of the second. The labeling for Blincyto contains a boxed warning about its risk of causing potentially life-threatening cytokine release syndrome (CRS) and neurologic toxicities. CRS is a systemic inflammatory response that may cause low blood pressure and difficulty breathing. Neurologic toxicities may include confusion, convulsions and encephalopathy. A Risk Evaluation and Mitigation Strategy (REMS) for Blincyto informs health care providers of its serious risks and also alerts them to the potential for preparation and administration errors. Its revised prescribing information is available here.

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