Clinical Newsletter Updates 1Q2019


Mavenclad approved for MS

Mavenclad®, a new formulation of cladribine, has been approved to treat adults who have multiple sclerosis (MS) and who have not been helped by or cannot tolerate other drugs for MS. Developed by EMD Serono, it can be used to treat relapsing-remitting disease (RRMS) and active secondary progressive disease (SPMS), but not for MS with clinically isolated syndrome. Dosing is based on the patient’s weight, with a minimum of 40kg (88 pounds). It is taken in two courses that each include two cycles. For each cycle, the patient takes 10mg or 20mg of Mavenclad once a day for four or five days. After 23 to 27 days, the cycle is repeated until a total dose of 1.75mg/kg is reached for the course. The patient then takes a break of 43 weeks or longer before repeating the two cycles and bringing the total dose to 3.5mg/kg. Further therapy with Mavenclad is not recommended. Tablets should be swallowed whole at least three hours before or after any other oral medications. They should be taken immediately after removal from the blister card and patients should wash their hands carefully after touching them. A boxed warning and patient Medication Guide outline its possible serious risks of causing cancers or birth defects. No pricing plans have been released. Prescribing information:

Cimzia Gains New Indication
Cimzia (certolizumab pegol) injection received a new indication for the treatment of adults with non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation, the first treatment approved for this condition.   Cimzia is already approved to treat adults with Crohn’s disease, moderate-to-severe rheumatoid arthritis, active psoriatic arthritis, active ankylosing spondylitis (AS), and moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.  Updated prescribing information:

First Generic for Remodulin
The FDA approved Tresprostinil, the first AP rated generic version of RemodulinTreprostinil, a prostacyclin vasodilator, is indicated for pulmonary arterial hypertension (PAH) (WHO Group 1) to reduce symptoms associated with exercise. It is also approved to reduce the rate of clinical deterioration in PAH patients who need to switch from epoprostenol sodium (
Flolan). Sandoz launched Tresprostinil on March 25th.
Jatenzo Approved
Jatenzo (testosterone undecanoate; Clarus Therapeutics) capsules has been approved for testosterone replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone: congenital or acquired primary hypogonadism or hypogonadotropic hypogonadism. Jatenzo is not intended for use in males with age-related hypogonadism and its safety and efficacy have not been established in males aged <18 years. Jatenzo carries a Boxed Warning describing an increase in blood pressure, increasing the risk of myocardial infarction, stroke, and cardiovascular death. Clinicians should assess the patient’s risk of heart disease and ensure adequately controlled blood pressure prior to initiating Jatenzo; periodic monitoring during treatment is also recommended.  Full prescribing information:

Mayzent approved for MS

Novartis received approval for Mayzent® (siponimod) tablets. It slows down disease progression for adult patients who have relapsing forms of multiple sclerosis (MS), including secondary progressive multiple sclerosis (SPMS) with active disease, relapsing remitting multiple sclerosis (RRMS) and clinically isolated syndrome (CIS). The first drug with a specific indication for SPMS, it reduces inflammation and stimulates remyelination in the central nervous system (CNS). Recommended maintenance dosing for most patients is 2mg daily after gradual dose increases starting at 0.25mg on the first day and reaching 1.25mg on day five. Some patients will be maintained on 1mg/day. Complete prescribing information:

Sunosi approved for patients with excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea (OSA).        

The FDA approved Jazz Pharmaceuticals’ Sunosi (solriamfetol). The drug, known as a dual-acting dopamine and norepinephrine reuptake inhibitor, is indicated to improve wakefulness in adult patients with excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea (OSA). The recommended starting dose, which is taken once-daily upon awakening, is 75mg for patients with narcolepsy and 37.5mg for patients with OSA. The dose may be increased every three days to a maximum dose of 150mg once daily. Launch, which depends on the timeline for scheduling as a controlled substance by the U.S. Drug Enforcement Agency (DEA), is planned for late June. Complete prescribing information:


Zulresso, the first drug specifically indicated to treat postpartum depression (PPD)

Zulresso (brexanolone – Sage Therapeutics) injection for infusion, is the first drug specifically indicated to treat postpartum depression (PPD). It is a neuroactive steroid gamma-aminobutyric acid (GABA)A receptor positive modulator that partially stimulates GABAA receptors in the brain. Zulresso will be given by trained healthcare providers in registered healthcare facilities as an intravenous (IV) infusion over 60 hours at varying dosage rates. Due to the risks of extreme sleepiness and lost or altered consciousness during the infusion, Zulresso has both a boxed warning and a risk evaluation and mitigation strategy (REMS). Patients, who must be enrolled in the REMS before receiving treatment, need continual monitoring during the entire infusion. Full antidepressive effects of Zulresso begin within a few days, however, as compared with the several weeks needed for most oral antidepressants to reach their peak effectiveness. Launch, which depends on the timeline for scheduling as a controlled substance by the U.S. Drug Enforcement Agency (DEA), is planned for late in June. Complete prescribing information:


Dupixent Receives Approval for One New Indication and an Expedited Review Date for Another

Dupixent received approval by the FDA for the treatment of moderate-to-severe atopic dermatitis in adolescent patients.  Currently, Dupixent is the only IL-4/IL-13 inhibitor therapy on the market, both interleukins are thought to play a key underlying role in atopic dermatitis.  Phase 3 trials demonstrated improved severity of disease, decreased itching, and resulted in clearer skin.  Trials for atopic dermatitis treatment in children ages 6-11 are currently underway with a target completion date by the end of the 2019.
Dupixent also received expedited FDA review status in treating adults with severe chronic sinusitis with nasal polyps.  Patients with severe chronic sinusitis with nasal polyps often experience recurrence of nasal polyps after nasal steroid therapy or surgery, making the condition notoriously difficult to manage in the long-run.  Phase 3 studies that evaluated nasal steroids plus Dupixent versus nasal steroids alone demonstrated significant reduction in nasal obstruction.  Additionally, the Dupixent group also yielded superior results compared to placebo at shrinking nasal polyps.  The FDA is expected to make a decision for this indication by June 26th.

New ADHD Treatment Approved 

The FDA approved Adhansia XR (methylphenidate HCl extended-release), a central nervous system stimulant, for the treatment of attention deficit hyperactivity disorder (ADHD) in patients 6 years and older.  It will be available later this year in 6 strengths and can be taken once-daily in the morning.  The capsules can either be swallowed or their contents sprinkled onto a soft food and consumed right away.  Adhansia XR cannot be substituted for other methylphenidate products.  Full prescribing information:

Janssen launches Nasal Spray indicated for adults with Major Depression

Janssen’s Spravato (esketamine) CIII nasal spray received approval from the U.S. Food and Drug Administration (FDA). It will be used, along with an oral antidepressant, for adult patients who have major depression that has not been relieved by two or more appropriate length and dose rounds of treatment with other antidepressants. Spravato will be available in single-use devices containing 28mg (two sprays). For the first four weeks, it will be dosed twice a week beginning at 56mg (two sprays followed by two more approximately five minutes later) for the first time, and then either 56mg or 84mg for the next seven treatments. For maintenance, the recommendation is either 56mg or 84mg once a week for the next four weeks, and then either dosed once a week or once every two weeks. Spravato will be distributed directly to certified treatment centers that have specially trained providers. Patients will administer Spravato, but they will be supervised by a healthcare professional during each treatment and then monitored for a minimum of two hours after. A boxed warning, a risk evaluation and treatment strategy (REMS) and a patient Medication Guide detail possible sedation, dissociation, suicidal thoughts and misuse associated with using Spravato. Complete prescribing information:

Self Injector for Tremfya Approved

The Food and Drug Administration approved Tremfya (guselkumab) One-Press, a single-dose patient-controlled injector for the treatment of 
moderate-to-severe plaque psoriasis in adults.  Tremfya is administered by subcutaneous injection.  Patients may use Tremfya One-Press, which provides a single dose of guselkumab 100mg, to self-inject the medication. Tremfya One-Press is available as a single-dose 100mg/mL patient-controlled injector; each One-Press injector can only be used once. Complete prescribing information can be found at:

Additional Indication for Soliqua Approved

Soliqua 100/33 received expanded indication to include use as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (T2DM) who are uncontrolled on oral antidiabetic agents, in addition to those inadequately controlled on basal insulin or lixisenatideSoliqua 100/33 is a combination of insulin glargine, a basal insulin analog, and lixisenatide, a GLP-1 receptor agonist. Updated prescribing information:

Herceptin Hylecta Approved

The FDA approved Herceptin Hylecta (trastuzumab and hyaluronidase-oysk) for the treatment of HER2-overexpressing breast cancer. Herceptin Hylecta is a combination of trastuzumab, an HER2/neu receptor antagonist.  The product contains the same active ingredient as 
Herceptin (trastuzumab) but is administered by subcutaneous (SC) injection.  Specifically, Herceptin Hylecta is indicated for adjuvant treatment of adults with HER2 overexpressing node positive or node negative (ER/PR negative or with 1 high risk feature) breast cancer: as part of a treatment regimen consisting of doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel; or as part of a treatment regimen with docetaxel and carboplatin; or as a single agent following multi-modality anthracycline based therapy. In addition, it is indicated for use in combination with paclitaxel for first-line treatment of HER2-overexpressing metastatic breast cancer and as a single agent for treatment of HER2-overexpressing breast cancer in patients who have received 1 or more chemotherapy regimens for metastatic disease. Patients should be selected for therapy based on an FDA-approved companion diagnostic for trastuzumab.   Prescribing information:

New Hemophilia A Treatment Approved

Novo Nordisk announced the approval of Esperoct (turoctocog alfa pegol, N8-GP) for the treatment of patients with 
Hemophilia A (congenital factor VIII deficiency) for routine prophylaxis to reduce the frequency of bleeding episodes, on-demand treatment and control of bleeding episodes and perioperative management of bleeding.  Esperoct is an extended half-life factor VIII molecule indicated for replacement therapy. Compared to standard half-life factor VIII products, Esperoct provides a 1.6-fold half-life prolongation in adults/adolescents and a 1.9-fold half-life prolongation in children.  Esperoct is not expected to be available in the US until 2020. 

Keytruda Receives a New Indication 

The FDA approved a new indication for Keytruda (pembrolizumab) for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection. This approval is the first for Keytruda in the adjuvant setting and the fourth for its use in skin cancers.  Updated prescribing information: 

Updated Label for Vemlidy 

Vemlidy ((tenofovir alafenamide) received approval for a labeling update. The update includes dosage information regarding its use in adults with end-stage renal disease (ESRD; CrCl <15mL/min) who are receiving chronic hemodialysis. The update states that no dosage adjustment of Vemlidy is needed in patients with mild, moderate, or severe renal impairment, or in patients with ESRD who are receiving chronic hemodialysis. On hemodialysis day, Vemlidy should be administered after hemodialysis is completed. Vemlidy is not recommended in patients with ESRD who are not receiving hemodialysis; the safety of Vemlidy has not been established in this population. Vemlidy is a nucleoside analogue (reverse transcriptase inhibitor) approved to treat chronic hepatitis B virus (HBV) infection in adults with compensated liver disease. It is available as 25mg tablets.  Updated information:

Cablivi First Drug Approved to Treat Acquired Thrombotic Thrombocytopenic Purpura

Cablivi® (caplacizumab-yhdp), the first drug that the FDA specifically has approved to treat acquired thrombotic thrombocytopenic purpura (aTTP), is indicated for use along with both an immunosuppressant and plasma exchange (plasmapheresis). aTTP is a rare disease that causes blood clots in small blood vessels. The first Cablivi treatment is given by a healthcare provider as a single intravenous (IV) injection 15 minutes or more before plasma exchange. A second dose is administered subcutaneously (SC) after the exchange is finished. Then, Cablivi is used as a once-a-day, SC injection that may be administered by the provider, the patient or a caregiver for 30 days beyond the last plasma exchange. If signs of persistent underlying disease remains after this course of therapy, treatment may be extended for a maximum of an additional 28 days. Complete prescribing information:



New Drug for Acute Migraines
The FDA approved Tosymra (sumatriptan nasal spray) for the acute treatment of migraines with or without aura in adults.  Tosymra is an intranasal spray containing sumatriptan 10mg, a selective 5-HT1B/1D receptor agonist. The spray contains a permeation-enhancing excipient (Intravail), which allows the product to be quickly absorbed into the systemic circulation while demonstrating a similar pharmacokinetic profile as subcutaneous (SC) sumatriptan.  Full prescribing information:

Imbruvica Approved for New Indication
Imbruvica (ibrutinib) received approval to be used in combination with obinutuzumab in treatment-naive patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), expanding the indication to include combination therapy as well as monotherapy.   Imbruvica is available as 70mg and 140mg capsules and as 140mg, 280mg, 420mg, and 560mg strength tablets; obinutuzumab (Gazyva) is available as a 25mg/mL strength solution for intravenous (IV) infusion. Updated prescribing information:

Osphena Receives New Indication
The FDA granted approval to Osphena to expand its use to include treatment of moderate to severe vaginal dryness, a symptom of vulvar and vaginal atrophy, due to menopause. Osphena is is an estrogen receptor agonist/antagonist with tissue selective effects. It was initially approved in 2013 to treat moderate to severe dyspareunia due to menopause. Osphena is available as 60mg tablets in 90-count bottles. Updated prescribing information:


Wixela Inhub First A-rated generic To Advair Diskus

Mylan’s Wixela Inhub (fluticasone propionate / salmeterol inhalation powder) received approval from the FDA, making it the first A-rated generic to GlaxoSmithKline’s Advair Diskus®. Mylan will market generics for all three currently marketed strengths of Advair Diskus: fluticasone propionate 100mcg/salmeterol 50mcg, 250mcg/50mcg and 500mcg/50mcg. It is unclear if GlaxoSmithKline plans to launch an authorized generic. Mylan launched Wixela Inhub during 1Q2019. Pricing and prescribing information are now available. 


Biosimilar, Otruzant, Approved
The FDA approved Ontruzant (trastuzumab-dttb), a biosimilar to Herceptin (trastuzumab).  Ontruzant, a HER2/neu receptor antagonist, is indicated for adjuvant treatment of HER2 overexpressing node positive or node negative (ER/PR negative or with 1 high risk feature breast cancer) as part of a treatment regimen consisting of doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel; as part of a treatment regimen with docetaxel and carboplatin; or as a single agent following multi-modality anthracycline based therapy. In addition, it is approved for use in combination with paclitaxel for first-line treatment of HER2-overexpressing metastatic breast cancer, and as a single agent, for treatment of HER2-overexpressing breast cancer in patients who have received 1 or more chemotherapy regimens for metastatic disease. Ontruzant is also approved for use in combination with cisplatin and capecitabine or 5-fluorouracil, for the treatment of patients with HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma who have not received prior treatment for metastatic disease. Complete prescribing information:


Cabometyx Receives New Approval
The Food and Drug Administration granted approval to Cabometyx (cabozantinib) for the treatment of hepatocellular carcinoma in patients who have been previously treated with Nexavar (sorafenib).  Cabometyx, a kinase inhibitor, is also approved for the treatment of patients with advanced renal cell carcinoma. The product is available in 20mg, 40mg, and 60mg tablets. The recommended dose of Cabometyx is 60mg once a day at least an hour before or two hours after eating. Prescribing information:

Sabril Generic Approved
Teva received approval for generic version of Sabril (vigabatrin) tablets for the treatment of refractory complex partial seizures (focal seizures) as adjunctive therapy in patients ≥10 years of age who have responded inadequately to several alternative treatments; it is not indicated as a first line agent.  As treatment with vigabatrin may be associated with permanent vision loss, the generic tablets are also part of a single shared-system Risk Evaluation and Mitigation Strategy (REMS) program to ensure the product is used safely. 

New Strengths of Apadaz Approved

The FDA approved two new strengths of Apadaz (benzhydrocodone, acetaminophen).  It was initially approved in February 2018 as 6.12mg/325mg immediate-release tablets and has now been approved for two new strengths of 4.08mg/325mg and 8.16mg/325mg.  Apadaz is used for short-term (no more than 14 days) management of acute pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.  Additional information can be found at:

Sprycel Receives New Indication

Sprycel (dasatinib) received a new indication to be used in combination with chemotherapy for the treatment of pediatric patients aged ≥1 year with newly diagnosed Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). Sprycel is already approved to treat: Ph+ chronic myeloid leukemia (CML) in chronic phase (CP) in children and adults; chronic, accelerated, or myeloid or lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib in adults; and Ph+ ALL with resistance or intolerance to prior therapy in adults.  Revised prescribing information:

Top Alzheimer’s Prospect Fails

Biogen and Eisai’s aducanumab phase 2 & 3 clinical trials were halted according to a statement by the companies on March 21st.  The early termination of the trial was based on a recommendation from an independent data review committee that concluded that it was unlikely that aducanumab group would reach the study’s primary endpoint of slowing cognitive and functional impairment in early Alzheimer ’s disease.  Aducanumab is a monoclonal antibody that reduces beta-amyloid plaque in the brain.  Beta-amyloid build-up in the brain is among the leading theories as to the underlying etiology of Alzheimer’s disease based on promising research in mice over 20 years ago.  However, all previous drug candidates that targeted the removal of beta-amyloid in the brain failed in clinical trials leaving researchers to review the ‘amyloid hypothesis’ that has driven much of the research in Alzheimer’s disease over the last two decades. 
Upon hearing of the news, some specialists are calling for a change in a paradigm of Alzheimer’s research to instead focus on early detection of the disease.  Some research suggests that amyloid deposition in the brain develops at least a decade prior to the appearance of Alzheimer’s symptoms.  In 2018 research groups in Japan and German both published research describing a novel blood test to detect beta-amyloid, specifically misfolded beta-amyloid that is associated with amyloid deposition in the brain.  If developed and commercialized, such blood tests may prove to be the key to earlier detection and treatment in the future.
Despite the announcement of the failure of aducanumab, on March 22nd Eisai announced they would begin phase 3 clinical trials of another Alzheimer’s prospect BAN2401.  The trial will be conducted in patients with mild cognitive impairment or mild Alzheimer’s disease with confirmed amyloid accumulation.  Previous BAN2401 data reported in July 2018 was met with mixed reviews resulting in lowered expectations for the experimental therapy’s ultimate success.    


Johnson & Johnson's Erleada Trial Ends Early
Johnson & Johnson (J&J) said investigators had cut short a phase 3 TITAN study of its prostate cancer drug Erleada in combination with androgen deprivation therapy (ADT) in patients with metastatic, castration-sensitive prostate cancer (mCSPC) after it was shown that the combination could significantly stave off disease progression and extend patients’ lives.
J&J recruited more than 1,050 patients with metastatic cases who were randomized to receive either Erleada plus ADT, or placebo plus ADT. They were treated “until disease progression or the occurrence of unacceptable treatment related toxicity, or end of treatment.” Based on the results, an independent data monitoring committee recommended placebo-plus-ADT patients switch over into the Erleada group.
Erleada is presently marketed in the United States for the treatment of men with non-metastatic castration-resistant prostate cancer (nmCRPC) who are at high risk of developing metastatic disease. Based on the results of this study, J&J said it will continue to evaluate overall survival and long-term safety, and plans to use the study data in an additional regulatory filing for Erleada.
"The TITAN study was designed to evaluate the efficacy and safety of Erleada in combination with androgen deprivation therapy in patients with newly-diagnosed metastatic castration-sensitive prostate cancer, regardless of the extent of their disease," said Margaret Yu, M.D., Vice President, Oncology Clinical Development, Janssen Research & Development. "We look to continue to build upon our understanding of Erleada for patients with metastatic prostate cancer as there remains a significant unmet need for additional treatment options."

Suboxone Generics Now Available
Generic versions of Suboxone (buprenorphine and naloxone sublingual film) are now available by generic companies Sandoz and Alvogen.  Suboxone is indicated for the treatment of 
opioid dependence, as part of a complete treatment plan that includes counseling and support. The CIII scheduled drug combines buprenorphine, a partial-opioid agonist, and naloxone, an opioid antagonist. Under the Drug Addiction Treatment Act (DATA), prescription use of this product in the treatment of opioid dependence is limited to healthcare providers who meet certain qualifying requirements, and who have notified the Secretary of Health and Human Services (HHS) of their intent to prescribe this product for the treatment of opioid dependence and have been assigned a unique identification number that must be included on every prescription. 


Xtandi Trial Yields Positive Results in New Population

Astellas and Pfizer’s Xtandi is currently approved for prostate cancer no longer responding to medical or surgical therapy designed to lower testosterone.  The drugmakers recently shared positive phase III trial results for patients with metastatic hormone sensitive prostate cancer.  The trial evaluated the radiographic progression-free survival (RPFS) of Xtandi plus androgen deprivation therapy (ADT) versus ADT alone.  The Xtandi plus ADT group demonstrated a 61% risk reduction of RPFS versus the ADT-only group.  Top-line safety results demonstrated rates of adverse effects consistent with those previously observed with Xtandi.  Both drugmakers feel that the data demonstrates this new combination may provide a valuable treatment option in men metastatic prostate cancer that has not yet become hormone resistant.  This new data will also help Xtandi keep pace with Johnson & Johnson’s Erleada, which in January demonstrated strong results when combined with ADT in patients with metastatic castration-sensitive prostate cancer.


MedWatch Update: Chantix

Results from a placebo-controlled study evaluating 
Chantix (varenicline) in pediatric patients 12-16 years of age showed that the smoking cessation treatment was not associated with a significant increase in abstinence rates in this patient population.  Due to these findings, the labeling for Chantix has been updated to specify that the drug is not recommended for use in pediatric patients 16 years of age or younger. Moreover, the efficacy of Chantix in patients 17-19 years of age could not be determined as the study was not powered to evaluate this age group, although these young adults were permitted to participate in the study.  More information is available at:


MedWatch Update: Uloric
The FDA strengthened previous safety warnings around Uloric by requiring a boxed warning and a patient medication guide for the drug used to treat gout.  It also requires the drug to be used in those cases where an alternative gout treatment cannot be used.   In a post-marketing clinical study that involved more than 6,000 participants, those taking Uloric had a higher chance of dying from a cardiovascular (CV) problem, such as a heart attack or stroke, than patients taking allopurinol.
Patients who do take Uloric are advised to seek immediate medical attention for chest pain, dizziness, irregular heartbeat, sudden headaches or other signs of possible CV events. For the full FDA notice, please see:

FDA Issues Warning Regarding Pfizer's Xeljanz

The FDA issued a warning regarding the increased risk of a pulmonary embolism and increased overall mortality in Pfizer’s post marketing trial assessing Xeljanz (tofacitinib) in rheumatoid arthritis patients.
When the FDA approved tofacitinib in 2012, it mandated that Pfizer undertake a clinical trial for patients with RA specifically to look for increased risks of cardiac events, malignancy, and opportunistic infections. Risks were analyzed for patients given tofacitinib in dosages of 5 mg or 10 mg twice daily, in combination with methotrexate, or a tumor necrosis factor (TNF) inhibitor.
A review of the study’s data by the Data Safety Monitoring Board revealed the safety risks in patients administered with 10mg of the drug.
Pfizer has transitioned patients from 10mg to 5mg of Xeljanz to address the risks.  The 5 mg dose is the approved dose for adult patients with moderate to severe rheumatoid arthritis.
"The FDA is actively examining the data from the trial and working directly with Pfizer to better understand the safety signal, its impact on patients, and how tofacitinib should be used," said Janet Woodcock, MD, director of the FDA's Center for Drug Evaluation and Research.  “We are communicating now, given the serious nature of the safety issue, to ensure that patients taking tofacitinib are aware that the FDA still believes the benefits of taking tofacitinib for its approved uses continue to outweigh the risks.”
In reaction to FDA’s drug safety communication, Pfizer spokesperson Neha Wadhwa said the company continues “to evaluate the risk benefit profile of tofacitinib across all indications and we will continue to work with regulators as more data become available.”