FDA APPROVALS

New FDA Drug Approvals in 2018 by Indication - Part 1

December 21, 2018

DERMATOLOGY

ILUMYA (tildrakizumab-asmn)

Manufacturer: Sun Pharma Global

Approval Date: March 20, 2018

FDA approved Ilumya, an interleukin-23 antagonist, for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. 

The FDA approval of Ilumya for the treatment of adults with moderate-to-severe plaque psoriasis was supported by data from two multicenter, randomized, double-blind, placebo-controlled trials (reSURFACE 1 and reSURFACE 2). A total of 926 adult patients were treated with Ilumya (N=616) or placebo (N=310). Both phase 3 studies met the primary efficacy endpoints, demonstrating significant clinical improvement with Ilumya 100 mg compared to placebo when measured by at least 75% of skin clearance (Psoriasis Area Sensitivity Index or PASI 75) and Physician's Global Assessment (PGA) score of "clear" or "minimal" at week 12 after two doses.

Of the patients in the reSURFACE 1 study, 74% (229 patients) achieved 75% skin clearance at week 28 after three doses, and 84% of patients who continued receiving Ilumya 100 mg maintained PASI 75 at week 64 compared to 22% of patients who were re-randomized to placebo. In addition, 69% of the patients receiving Ilumya 100 mg who had a PGA score of "clear" or "minimal" at week 28 maintained this response at week 64 compared to 14% of patients who were re-randomized to placebo.

The most common (≥1%) adverse reactions associated with Ilumya include upper respiratory infections, injection site reactions, and diarrhea. Adverse reactions that occurred at rates less than 1% but greater than 0.1% in the Ilumya group and at a higher rate than in the placebo group included dizziness and pain in extremity. Cases of angioedema and urticaria occurred in Ilumya-treated subjects in clinical trial. 

Ilumya is administered at a dose of 100 mg by subcutaneous injection every 12 weeks, after the completion of initial doses at weeks 0 and 4. Ilumya is contraindicated in patients with a previous serious hypersensitivity reaction to tildrakizumab or to any of the excipients.

QBREXZA (glycopyrronium tosylate)

Manufacturer: Dermira Inc

Approval Date: June 28, 2018

FDA approved Qbrexza, an anticholinergic, for topical treatment of primary axillary hyperhidrosis (excessive underarm sweating) in adults and pediatric patients 9 years of age and older.

The FDA approval of Qbrexza was based on results from two phase 3 clinical trials, ATMOS-1 and ATMOS-2, which evaluated the efficacy
and safety of Qbrexza in patients with primary axillary hyperhidrosis. Both trials showed improvements in the absolute change from baseline in sweat production following treatment with Qbrexza and the proportion of patients who achieved at least a four-point improvement from baseline in their sweating severity, as measured by the Axillary Sweating Daily Diary (ASDD).

The most common side effects observed following topical application of Qbrexza to the underarms were dry mouth, dilated pupil (mydriasis), sore throat (oropharyngeal pain), headache, urinary hesitation, blurred vision, dry nose, dry throat, dry eye, dry skin, and constipation. The most common local skin reactions were erythema, burning/stinging, and pruritus.

Qbrexza is applied directly to the skin and is designed to block sweat production by inhibiting sweat gland activation.

 

SEYSARA (sarecycline)

Manufacturer: Allergan Inc

Approval Date: October 1, 2018

FDA approved Seysara, a first-in-class tetracycline-derived oral antibiotic, for the treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris in patients 9 years of age and older. 

The approval was based on evidence from three clinical trials of 2133 patients 9 to 45 years of age with moderate to severe acne vulgaris.

Trials 1 and 2 enrolled patients 9 to 45 years of age with moderate to severe facial acne vulgaris. Patients received Seysara or placebo tablets by mouth once daily for 12 weeks. Neither the patients nor the health care providers knew which treatment was being given until after the trial was completed. The benefit of Seysara in comparison to placebo was assessed after 12 weeks of treatment using the Investigator’s Global Assessment (IGA) score that measures the severity of disease (on a scale from 0 to 4) and a decrease in the number of inflammatory acne (pimples).

Trial 3 enrolled patients 12 to 45 years of age with moderate to severe facial acne vulgaris. Patients received one of three doses of Seysara capsules by mouth for 12 weeks. Patients in Trial 3 were primarily evaluated for side effects. Mean absolute and percent reduction in inflammatory lesions was greater with Seysara compared to placebo at Week 12 for both studies. 

The only adverse drug reaction that was reported in at least 1% of subjects was nausea, Seysara (3.1%) versus placebo (2.0%). The following additional adverse drug reactions occurred in less than 1% of female Seysara subjects: vulvovaginal mycotic infection (0.8%) and vulvovaginal candidiasis (0.6%).

Seysara is an oral tablet that is taken once daily with or without food.

BRYHALI (halobetasol propionate)

Manufacturer: Bausch Health

Approval Date: November 6, 2018

FDA approved Bryhali lotion .01% for up to 8 weeks of use for the topical treatment of plaque psoriasis in adults.

Data from two phase 3 multicenter, double-blind trials supported the FDA’s decision. The trials included patients with plaque psoriasis covering a body surface area of 3-12%. In trial 1, 217 participants were randomized to either halobetasol propionate lotion .01% (n = 143) or unmedicated vehicle lotion (n = 74). In trial 2 (n = 213), those numbers were 142 and 71, respectively. After 8 weeks of daily treatment application to areas affected by plaque psoriasis, there was a 4-week period without treatment and a follow-up visit to evaluate efficacy and safety. Disease severity was measured at weeks 2, 4, 6, 8, and 12 by a 5-grade Investigator’s Global Assessment (IGA). Treatment success was defined as ≥2-grade improvement in IGA from baseline and an IGA score equivalent to “clear” or “almost clear” at week 8. In trial 1, 37% of participants in the Bryhali lotion group were successfully treated, compared with 8% of the vehicle group; in trial 2, those numbers were 38% and 12%, respectively. Bryhali lotion demonstrated statistically significant treatment success over vehicle as early as week 2 in trial 1 and week 4 in trial 2, which continued through week 12.

The most common adverse reactions (≥1%) were upper respiratory tract infection (2%), application site dermatitis (1%), and hyperglycemia (1%).

Treatment is recommended for only as long as necessary to achieve control, and no longer than 8 weeks.

 

GENETIC DISEASES

CRYSVITA (burosumab-twza)

Manufacturer: Ultragenyx Pharm Inc

Approval Date: April 17, 2018

FDA approved Crysvita, the first drug approved to treat adults and children ages 1 year and older with x-linked hypophosphatemia (XLH), a rare, inherited form of rickets.

The safety and efficacy of Crysvita were studied in four clinical trials. In the placebo-controlled trial, 94% of adults receiving Crysvita once a month achieved normal phosphorus levels compared to 8% of those receiving placebo. In children, 94% to 100% of patients treated with Crysvita every 2 weeks achieved normal phosphorus levels. In both children and adults, X-ray findings associated with XLH improved with Crysvita therapy. Comparison of the results to a natural history cohort also provided support for the effectiveness of Crysvita.

The most common adverse reactions in adults taking Crysvita were back pain, headache, restless leg syndrome, decreased vitamin D, dizziness and constipation. The most common adverse reactions in children were headache, injection site reaction, vomiting, decreased vitamin D and pyrexia (fever).

The recommended starting dose regimen is 0.8 mg/kg of body weight, rounded to the nearest 10 mg, administered every 2 weeks.

 

PALYNZIQ (pegvaliase-pqpz)

Manufacturer: Biomarin Pharmaceuticals

Approval Date: May 24, 2018

FDA approved Palynziq for adults with a rare and serious genetic disease known as phenylketonuria (PKU). Patients with PKU are born with an inability to break down phenylalanine (Phe), an amino acid present in protein-containing foods and high-intensity sweeteners used in a variety of foods and beverages. Palynziq is a novel enzyme therapy for adult PKU patients who have uncontrolled blood Phe concentrations on current treatment.

The safety and efficacy of Palynziq were studied in two clinical trials in adult patients with PKU with blood phenylalanine concentrations greater than 600 µmol/L on existing management. Most PKU patients in the Palynziq trials were on an unrestricted diet prior to and during the trials. The first trial was a randomized, open-label trial in patients treated with increasing doses of Palynziq administered as a subcutaneous injection up to a target dose of either 20 mg once daily or 40 mg once daily. The second trial was an 8-week, placebo-controlled, randomized withdrawal trial in patients who were previously treated with Palynziq. Patients treated with Palynziq achieved statistically significant reductions in blood phenylalanine concentrations from their pre-treatment baseline blood Phe concentrations.

The most common adverse events reported in the Palynziq trials included injection site reactions, joint pain, hypersensitivity reactions, headache, generalized skin reactions lasting at least 14 days, pruritus (itchy skin), nausea, dizziness, abdominal pain, throat pain, fatigue, vomiting, cough and diarrhea. Hypersensitivity reactions occurred in most patients, likely due to formation of antibodies to the product. The most serious adverse reaction in the Palynziq trials was anaphylaxis, which occurred most frequently during upward titration of the dose within the first year of treatment. Because of this serious risk, the labeling for Palynziq includes a Boxed Warning and the product is available only through a restricted program under a REMS program.

Palynziq is a daily at-home subcutaneous injection available in 3 dosage strengths: 2.5 mg/0.5 mL, 10 mg/0.5 mL, and 20 mg/mL.

 

GALAFOLD (migalastat hydrochloride)

Manufacturer: Amicus Therapeutics

Approval Date: August 10, 2018

FDA approved Galafold, the first oral medication for the treatment of adults with Fabry disease who have an amenable galactosidase alpha gene (GLA) variant based on in vitro assay data. Galafold is approved for 348 amenable GLA variants.

Galafold is the first oral medicine for Fabry disease, and the first new therapy approved to treat Fabry disease in the United States in more than 15 years.

Fabry disease is a rare and serious genetic disease that results from buildup of a type of fat called globotriaosylceramide (GL-3) in blood vessels, the kidneys, the heart, the nerves, and other organs.

The efficacy of Galafold was demonstrated in a 6-month, placebo-controlled clinical trial in 45 adults with Fabry disease. In this trial, patients treated with Galafold over 6 months had a greater reduction in GL-3 in blood vessels of the kidneys (as measured in kidney biopsy samples) as compared with patients on placebo.

The safety of Galafold was studied in four clinical trials which included a total of 139 patients with Fabry disease. The most common adverse drug reactions in patients taking Galafold in clinical trials were headache, nasal and throat irritation (nasopharyngitis), urinary tract infection, nausea, and fever (pyrexia).

Galafold is a capsule taken once every other day, at the same time of day.

 

ONPATTRO (patisiran sodium)

Manufacturer: Alnylam Pharmaceuticals

Approval Date: August 10, 2018

FDA approved Onpattro infusion for the treatment of peripheral nerve disease (polyneuropathy) caused by hereditary transthyretin-mediated amyloidosis (hATTR) in adult patients.

This is the first FDA-approved treatment for patients with polyneuropathy caused by hATTR, a rare, debilitating and often fatal genetic disease characterized by the buildup of abnormal amyloid protein in peripheral nerves, the heart and other organs. It is also the first FDA approval of a new class of drugs called small interfering ribonucleic acid (siRNA) treatment.

Onpattro is designed to interfere with RNA production of an abnormal form of the protein transthyretin (TTR). By preventing the production of TTR, the drug can help reduce the accumulation of amyloid deposits in peripheral nerves, improving symptoms and helping patients better manage the condition.

The efficacy of Onpattro was shown in a clinical trial involving 225 patients, 148 of whom were randomly assigned to receive an Onpattro infusion once every 3 weeks for 18 months, and 77 of whom were randomly assigned to receive a placebo infusion at the same frequency. The patients who received Onpattro had better outcomes on measures of polyneuropathy including muscle strength; sensation (pain, temperature, numbness); reflexes; and autonomic symptoms (blood pressure, heart rate, digestion) compared to those receiving the placebo infusions. Onpattro-treated patients also scored better on assessments of walking, nutritional status and the ability to perform activities of daily living.

The most common adverse reactions reported by patients treated with Onpattro are infusion-related reactions including flushing, back pain, nausea, abdominal pain, dyspnea (difficulty breathing), and headache. All patients who participated in the clinical trials received premedication with a corticosteroid, acetaminophen, and antihistamines (H1 and H2 blockers) to reduce the occurrence of infusion-related reactions. Patients may also experience vision problems including dry eyes, blurred vision, and eye floaters (vitreous floaters). Onpattro leads to a decrease in serum vitamin A levels, so patients should take a daily vitamin A supplement at the recommended daily allowance.

 

TAKHZYRO (lanadelumab)

Manufacturer: Shire

Approval Date: August 23, 2018

FDA approved Takhzyro, the first monoclonal antibody approved in the US to treat patients 12 years and older with types I and II hereditary angioedema (HAE), a rare and serious genetic disease that affects people with low levels of and poorly functioning C1-INH proteins in the body. Takhzyro is a plasma kallikrein inhibitor that is used to prevent swelling attacks from occurring.

FDA based its approval on data from a multicenter, randomized, double-blind, placebo-controlled, parallel-group study in 125 patients with HAE. Patients who received Takhzyro had clinically meaningful and statistically significant reductions in the rate of investigator-confirmed HAE attacks compared to placebo over a 6-month treatment period.

The most common adverse drug reactions in patients taking Takhzyro in clinical trials were injection site reactions, upper respiratory infections, headache, rash, muscle pain, dizziness, and diarrhea.

 

REVCOVI (elapegademase-lvlr)

Manufacturer: Leadiant Biosciences Inc

Approval Date: October 5, 2018

FDA granted approval to Revcovi injection, a new enzyme replacement therapy, for the treatment of adenosine deaminase severe combined immune deficiency (ADA-SCID) in pediatric and adult patients.

The FDA approved Revcovi based on evidence from two clinical trials (Trial 1 and Trial 2) of 10 patients with ADA-SCID. Trial 1 was conducted in the United States and Trial 2 in Japan.

Trial 1 enrolled patients who were receiving adagen for ADA-SCID. All patients received a once weekly IM dose of adagen for at least 3 weeks followed by weekly IM doses of Revcovi for 21 weeks. The benefit of Revcovi was assessed based on activity of the ADA enzyme activity for Weeks 15, 17, 19 and 21. Patients achieved complete detoxification based on trough dAXP level and trough plasma ADA activity and showed stable or slightly increased lymphocyte counts during Revcovi treatment relative to values recorded during the adagen lead-in phase.

Trial 2 enrolled adult and pediatric patients with ADA-SCID. All patients received weekly IM doses of REVCOVI for 21 weeks. The benefit of REVCOVI was assessed based on activity of the ADA enzyme activity. All four of the patients in Study 2 achieved and maintained detoxification (trough dAXP [erythrocyte or blood] ≤0.02 mmol/L) throughout their participation in the Treatment Phase of 21 weeks. Serum ADA activity increased after administering Revcovi for all four patients, with three patients achieving activity level over 15 mmol/hr/L during the Dose Maintenance Period. Total lymphocyte counts and B-/T-/NK-lymphocyte subset counts for three patients increased from screening to Day 15 during dose adjustment and were stable or increasing during the Maintenance Period.

Revcovi may cause serious side effects including injection site bleeding in patients with low platelet counts. The most common side effects are cough and vomiting.

 

TEGSEDI (inotersen)

Manufacturer: Ionis Pharmaceuticals

Approval Date: October 5, 2018

FDA has approved Tegsedi, a transthyretin-directed antisense oligonucleotide, for the treatment of the polyneuropathy of hATTR in adults. 

The FDA’s approval of Tegsedi was based on results from the phase 3 NEURO-TTR study in patients with hATTR amyloidosis with symptoms of polyneuropathy. Results from that study demonstrated that patients treated with Tegsedi experienced significant benefit compared to patients treated with placebo across both co-primary endpoints: the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN) and modified Neuropathy Impairment Score +7 (mNIS+7), a measure of neuropathic disease progression.

Tegsedi is associated with risk of thrombocytopenia and glomerulonephritis. Enhanced monitoring is required to support early detection and management of these identified risks. Tegsedi is being marketed with a REMS.

HEMATOLOGY

 

TAVALISSE (fostamatinib disodium)

Manufacturer: Rigel Pharmaceuticals Inc

Approval Date: April 17, 2018

FDA approved Tavalisse for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment. Tavalisse is a kinase inhibitor. 

Approval was based on two identical, double-blind, placebo-controlled trials, FIT-1 and FIT-2, that enrolled a total of 150 patients with persistent or chronic ITP who had an insufficient response to previous treatment, which included corticosteroids, immunoglobulins, splenectomy, and/or a thrombopoietin receptor agonist. Patients were randomized 2:1 to fostamatinib (100 mg orally twice daily) or placebo for 24 weeks. Dose could be escalated to 150 mg orally twice daily after 1 month.

Efficacy was based on stable platelet response (at least 50 x109/L on at least 4 of the 6 visits between Weeks 14 to 24). In FIT-1, stable platelet response was demonstrated in 18% (n=9) of patients receiving fostamatinib compared with 0% (n=0) of patients receiving placebo (P = .03). In FIT-2, stable platelet response was seen in 16% (n=8) and 4% (n=1) of patients, respectively (P = .26). In the FIT-3 extension study, a stable response was observed in 23% (n=10) of patients newly exposed to fostamatinib. Durable platelet responses were seen in FIT-1, FIT-2, and the FIT-3 extension study.

The most common adverse reactions in at least 5% of patients treated with fostamatinib were diarrhea, hypertension, nausea, dizziness, alanine aminotransferase/aspartate aminotransferase (ALT/AST) increased, respiratory infection, rash, abdominal pain, fatigue, chest pain, and neutropenia. In the ITP double-blind studies, serious adverse drug reactions were febrile neutropenia, diarrhea, pneumonia, and hypertensive crisis, which each occurred in 1% of patients receiving fostamatinib.

The recommended dose initially is 100 mg administered orally twice daily. After a month, if platelet count has not increased to at least 50x109/L, increase dose to 150 mg twice a day.

 

RETACRIT (epoetin alfa-epbx)

Manufacturer: Hospira Inc, a subsidiary of Pfizer Inc

Approval Date: May 15, 2018

FDA approved Retacrit as a biosimilar to Epogen/Procrit (epoetin alfa, Amgen Inc) for the treatment of anemia due to chronic kidney disease (CKD) in patients on dialysis and not on dialysis; use of zidovudine in patients with HIV infection; and the effects of concomitant myelosuppressive chemotherapy. It is also approved for the reduction of allogeneic red blood cell transfusions in patients undergoing elective, noncardiac, nonvascular surgery.

The approval was based on comparisons of extensive structural and functional product characterization, animal data, human pharmacokinetic and pharmacodynamic data, and clinical immunogenicity between Retacrit and US-licensed Epogen/Procrit demonstrating that Retacrit is highly similar to Epogen/Procrit and that there are no clinically meaningful differences between the products. Retacrit has not been shown to be interchangeable with Epogen/Procrit.

Like Epogen/Procrit, the labeling for Retacrit contains a Boxed Warning to alert health care professionals and patients about an increased risk of death, myocardial infarction, stroke, venous thromboembolism, thrombosis of vascular access, and tumor progression or recurrence.

 

LOKELMA (sodium zirconium cyclosilicate)

Manufacturer: AstraZeneca Pharmaceuticals

Approval Date: May 18, 2018

FDA approved Lokelma, a potassium binder, for the treatment of hyperkalemia in adults.

The FDA approval is supported by data from three double-blind, placebo-controlled trials and two open-label trials, which showed that, for patients receiving Lokelma, the onset of action was at 1.0 hour and the median time to achieving normal potassium levels in the blood was 2.2 hours, with 92% of patients achieving normal potassium levels within 48 hours from baseline. The treatment effect was maintained for up to 12 months.

Common side effects of Lokelma include mild to moderate swelling (edema).

Lokelma is an insoluble, non-absorbed sodium zirconium silicate, formulated as a powder for oral suspension, that acts as a highly-selective potassium-removing agent. It is administered orally.

 

DOPTELET (avatrombopag maleate)

Manufacturer: Akarx Inc

Approval Date: May 21, 2018

FDA approved Doptelet, a thrombopoietin receptor agonist, for the treatment of thrombocytopenia in adult patients with chronic liver disease who are scheduled to undergo a procedure. This is the first drug approved by the FDA for this use.

The safety and efficacy of Doptelet was studied in two trials (ADAPT-1 and ADAPT-2) involving 435 patients with chronic liver disease and severe thrombocytopenia who were scheduled to undergo a procedure that would typically require platelet transfusion. The trials investigated two dose levels of Doptelet administered orally over 5 days as compared to placebo (no treatment). The trial results showed that for both dose levels of Doptelet, a higher proportion of patients had increased platelet counts and did not require platelet transfusion or any rescue therapy on the day of the procedure and up to 7 days following the procedure as compared to those treated with placebo.

The most common side effects reported by clinical trial participants who received Doptelet were fever, stomach (abdominal) pain, nausea, headache, fatigue and swelling in the hands or feet (edema). People with chronic liver disease and people with certain blood clotting conditions may have an increased risk of developing blood clots when taking Doptelet.

 

FULPHILA (pegfilgrastim-jmdb)

Manufacturer: Mylan GmbH

Approval Date: June 4, 2018

FDA approved Fulphila as a biosimilar to Neulasta (pegfilgrastim, Amgen, Inc) to decrease the chance of infection as suggested by febrile neutropenia in patients with non-myeloid cancer who are receiving myelosuppressive chemotherapy that has a clinically significant incidence of febrile neutropenia.

The approval was based on comparisons of extensive structural and functional product characterization, animal data, human pharmacokinetic and pharmacodynamic data, clinical immunogenicity, and other clinical safety and effectiveness data demonstrating that Fulphila is biosimilar to Neulasta. Fulphila has been approved as a biosimilar, not as an interchangeable product.

The most common side effects of Fulphila are bone pain and pain in extremities. Patients with a history of serious allergic reactions to human granulocyte colony-stimulating factors such as pegfilgrastim or filgrastim products should not take Fulphila. Serious side effects from treatment with Fulphila include rupture of the spleen, acute respiratory distress syndrome, serious allergic reactions including anaphylaxis, glomerulonephritis, leukocytosis, capillary leak syndrome, and the potential for tumor growth. Fatal sickle cell crises have occurred.

 

TIBSOVO (ivosidenib)

Manufacturer: Agios Pharmaceuticals Inc

Approval Date: July 20, 2018

FDA approved Tibsovo for adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible IDH1 mutation as detected by an FDA-approved test. This is the first drug in its class (IDH1 inhibitors) and is approved for use with an FDA-approved companion diagnostic used to detect specific mutations in the IDH1 gene in patients with AML.

Approval was based on an open-label, single-arm, multicenter clinical trial (AG120-C-001) that included 174 adult patients with relapsed or
refractory AML with an IDH1 mutation confirmed using the Abbott RealTime IDH1 Assay, the FDA-approved test for selection of patients with AML for treatment with Tibsovo. Tibsovo was given orally at a starting dose of 500 mg daily until disease progression, unacceptable toxicity, or hematopoietic stem cell transplantation. The median treatment duration was 4.1 months (range, 0.1 to 39.5 months). Twenty-one of the 174 patients (12%) received a stem cell transplant following Tibsovo treatment.

Efficacy was established on the basis of the rate of complete remission (CR) plus complete remission with partial hematologic recovery (CRh), CR+CRh duration, and the rate of conversion from transfusion dependence to independence. The CR+CRh rate was 32.8% (95% CI: 25.8-40.3). The median time-to-response was 2 months (range, 0.9-5.6 months), and the median response duration was 8.2 months (95% CI: 5.6 -12 months). The CR and CRh rates were 24.7% (95% CI: 18.5, 31.8) and 8.0% (95% CI: 4.5, 13.1), respectively.

Among the 110 patients who were dependent on red blood cell (RBC) and/or platelet transfusions at baseline, 41 (37.3%) became independent of RBC and platelet transfusions during any 56-day post-baseline period. Of the 64 patients who were independent of both RBC and platelet transfusions at baseline, 38 (59.4%) remained transfusion independent during any 56-day post-baseline period.

The most common adverse reactions (≥20%) were fatigue, leukocytosis, arthralgia, diarrhea, dyspnea, edema, nausea, mucositis, electrocardiogram QT prolonged, rash, pyrexia, cough, and constipation.

The FDA also approved the Abbott RealTime IDH1 Assay for use in selecting patients for treatment with Tibsovo.

The recommended Tibsovo dose is 500 mg orally once daily with or without food until disease progression or unacceptable toxicity. For patients without disease progression or unacceptable toxicity, treatment is recommended for a minimum of 6 months to allow time for clinical response.

 

NIVESTYM (filgrastim-aafi)

Manufacturer: Hospira Inc

Approval Date: July 20, 2018

FDA approved Nivestym as a biosimilar to Neupogen (filgrastim; Amgen, Inc), a leukocyte growth factor, for all eligible indications of the reference product.

The FDA approval was based on a review of a comprehensive data package and totality of evidence demonstrating a high degree of similarity of Nivestym compared to its reference product.

In the US, Nivestym is indicated:

To decrease the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a significant incidence of severe neutropenia with fever.

For reducing the time to neutrophil recovery and the duration of fever, following induction or consolidation chemotherapy treatment of patients with AML.

To reduce the duration of neutropenia and neutropenia-related clinical sequelae, eg, febrile neutropenia, in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplantation (BMT).

For the mobilization of autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis.

For chronic administration to reduce the incidence and duration of sequelae of severe neutropenia (eg, fever, infections, oropharyngeal ulcers) in symptomatic patients with congenital neutropenia, cyclic neutropenia, or idiopathic neutropenia.

 

MULPLETA (lusutrombopag)

Manufacturer: Shionogi Inc

Approval Date: July 31, 2018

FDA approved Mulpleta, a once-daily, orally administered, small molecule thrombopoietin (TPO) receptor agonist for the treatment of thrombocytopenia in adult patients with chronic liver disease (CLD) who are scheduled to undergo a procedure.

The FDA approval was based on safety and efficacy data from two phase 3 randomized, double-blind, placebo-controlled trials, L-PLUS 1 (N=97) and L-PLUS 2 (N=215), involving patients with chronic liver disease who were undergoing an invasive procedure and had a platelet count <50 x 109/L. Patients were randomized to Mulpleta 3 mg or placebo once daily for 7 days. In L‐PLUS 1, the major efficacy outcome was the proportion of patients who required no platelet transfusion prior to the primary invasive procedure, while in L‐PLUS 2, it was the proportion of patients who required no platelet transfusion prior to the primary invasive procedure and no rescue therapy for bleeding from randomization through 7 days after the primary invasive procedure. In both trials, responders were defined as patients who had a platelet count of ≥50 x 109/L with an increase of ≥20 x 109/L from baseline.

In L-PLUS 1, 78% of patients (38/49) receiving Mulpleta required no platelet transfusion prior to the invasive procedure, compared with 13% (6/48) who received placebo (treatment difference: 64%; P <.0001). Seventy-six percent of Mulpleta-treated patients were considered responders vs 6% of patients in the placebo arm (treatment difference: 68%; P <.0001). In L-PLUS 2, 65% (70/108) of patients who received Mulpleta required no platelet transfusion prior to the invasive procedure or rescue therapy for bleeding through 7 days after the procedure, compared with 29% (31/107) receiving placebo (treatment difference: 37%; P <.0001). Sixty-five percent of Mulpleta-treated patients were considered responders vs 13% of patients in the placebo group (treatment difference: 52%; P <.0001).

The most common adverse reaction associated with therapy in clinical trials was headache.

Mulpleta, a thrombopoietin receptor agonist, will be supplied in 3mg strength tablets in blister packs containing 7 tablets.

 

POTELIGEO (mogamulizumab-kpkc) 

Manufacturer: Kyowa Kirin Inc

Approval Date: August 8, 2018

FDA approved Poteligeo for adult patients with relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS) after at least one prior systemic therapy.

The approval of Poteligeo, a CC chemokine receptor type 4 (CCR4) directed monoclonal antibody, was based on a randomized, open-label, multicenter trial (Study 0761-010) in patients with active MF or SS after at least one prior systemic therapy. Patients enrolled had a median of three prior therapies. The trial randomized 372 patients (44% with SS) to either Poteligeo or vorinostat.

PFS was statistically significantly longer in the Poteligeo arm. The estimated median PFS was 7.6 months (95% CI: 5.6, 10.2) for those treated with Poteligeo compared with 3.1 months (95% CI: 2.8, 4.0) in the vorinostat arm (hazard ratio 0.53; 95% CI: 0.41, 0.69). The confirmed overall response rate was 28% and 5%, respectively (P < .001).

The most common adverse reactions (reported in ≥20%) were rash, infusion-related reactions, fatigue, diarrhea, musculoskeletal pain, and upper respiratory tract infection. Serious adverse reactions occurred in 36% of patients, most often from infection (16% of all patients). The prescribing information includes warnings for dermatologic toxicity, infusion reactions, infections, autoimmune complications, and complications of allogeneic hematopoietic stem cell transplantation, including severe and refractory graft-versus-host disease.

The recommended Poteligeo dose is 1 mg/kg administered as an intravenous infusion over at least 60 minutes. Poteligeo is administered on days 1, 8, 15, and 22 of the first 28-day cycle, then on days 1 and 15 of subsequent 28-day cycles until disease progression or unacceptable toxicity.

 

LUMOXITI (moxetumomab pasudotox-tdfk)

Manufacturer: AstraZeneca Pharmaceuticals

Approval Date: September 13, 2018

FDA approved Lumoxiti, a CD22-directed cytotoxin indicated for adult patients with relapsed or refractory hairy cell leukemia (HCL) who received at least two prior systemic therapies, including treatment with a purine nucleoside analog (PNA).

Lumoxiti is a CD22-directed cytotoxin and is the first of this type of treatment for patients with HCL, providing the first FDA-approved medicine for this condition in more than 20 years.

Approval was based on Study 1053 in patients with histologically confirmed HCL or HCL variant requiring treatment based on presence of cytopenias or splenomegaly and who had received prior treatment with at least two systemic therapies, including one PNA. Eligible patients had serum creatinine ≤ 1.5 mg/dL or creatinine clearance ≥ 60 mL/min as estimated by the Cockcroft Gault equation. A total of 80 patients were enrolled; 77 with classic HCL and 3 with HCL variant. Patients received Lumoxiti 0.04 mg/kg as an intravenous infusion over 30 minutes on days 1, 3, and 5 of each 28-day cycle for a maximum of 6 cycles or until documentation of CR, disease progression, or unacceptable toxicity.  

Efficacy in HCL was evaluated by the blinded independent review committee (IRC)-assessed rate of durable complete response (CR) confirmed by maintenance of hematologic remission (hemoglobin ≥ 11 g/dL, neutrophils ≥ 1500/mm3, and platelets ≥ 100,000/mm3 without transfusions or growth factor for at least 4 weeks) more than 180 days after independent review committee (IRC)-assessed CR. The IRC-assessed durable CR rate was 30% (24/80 patients; 95% CI: 20, 41). The IRC-assessed CR rate was 41% (33/80 patients; 95% CI: 30, 53).

The most common non-laboratory adverse reactions (≥20%) of any grade were infusion-related reactions, edema, nausea, fatigue, headache, pyrexia, constipation, anemia, and diarrhea. The most common grade 3 or 4 adverse reactions (reported in at least ≥ 5% of patients) were hypertension, febrile neutropenia, and hemolytic uremic syndrome (HUS). Adverse reactions resulting in permanent discontinuation of Lumoxiti occurred in 15% (12/80) of patients. The most common adverse reaction leading to discontinuation was HUS (5%). The most common adverse reactions resulting in dose delays, omissions, or interruptions was pyrexia (3.8%).

The recommended dose of Lumoxiti is 0.04 mg/kg administered as a 30-minute intravenous infusion on days 1, 3, and 5 of each 28-day cycle for a maximum of 6 cycles or until occurrence of disease progression or unacceptable toxicity.

 

COPIKTRA (duvelisib)

Manufacturer:  Verastem Inc

Approval Date: September 24, 2018

FDA granted regular approval to Copiktra for adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) after at least two prior therapies. In addition, Copiktra received accelerated approval for adult patients with relapsed or refractory follicular lymphoma (FL) after at least two prior systemic therapies.

The CLL and SLL indication is based on a randomized, multicenter, open-label trial comparing Copiktra to ofatumumab in patients with relapsed or refractory CLL or SLL. The trial randomized patients (1:1) to either Copiktra 25 mg orally twice daily or ofatumumab. Ofatumumab was administered intravenously at an initial dose of 300 mg, followed one week later by 2000 mg once weekly for 7 doses, and then 2000 mg once every 4 weeks for 4 additional doses.

Among 196 patients receiving at least 2 prior therapies (95 randomized to Copiktra, 101 to ofatumumab), the estimated median progression-free survival, as assessed by an IRC, was 16.4 months in the Copiktra arm and 9.1 months in the ofatumumab arm (HR: 0.40; standard error: 0.2). The ORR per IRC was 78% and 39% for the duvelisib and ofatumumab arms, respectively (39% difference, standard error: 6.5%).

The FL indication is based on a single-arm multicenter trial of Copiktra enrolling 83 patients with FL who were refractory to rituximab and to either chemotherapy or radioimmunotherapy. The overall response rate (ORR), determined by an IRC, was 42% (95% CI: 31, 54), with 41% of patients experiencing partial responses and one patient having a CR. Of the 35 responding patients,15 (43%) maintained responses for at least 6 months and 6 (17%) maintained responses for at least 12 months. Continued approval for the FL indication may be contingent upon verification of clinical benefit demonstrated in a planned randomized trial.

The prescribing information contains Boxed Warnings for fatal and/or serious infections, diarrhea or colitis, cutaneous reactions, and pneumonitis and warnings for neutropenia and hepatotoxicity. Of 442 patients with hematologic malignancies treated with Copiktra at the approved dose, 65% had serious adverse reactions, with the most frequent being infection, diarrhea or colitis, and pneumonia. The most common adverse reactions (incidence ≥ 20%) were diarrhea or colitis, neutropenia, rash, fatigue, pyrexia, cough, nausea, upper respiratory infection, pneumonia, musculoskeletal pain, and anemia. Adverse reactions resulted in permanent discontinuation of Copiktra in 35% of patients. Dose reduction occurred in 24%.

The recommended Copiktra dose is 25 mg orally twice daily, taken continuously in 28-day treatment cycles.

 

UDENYCA (pegfilgrastim-cbqv)

Manufacturer: Coherus Biosciences Inc

Approval Date: November 2, 2018

FDA approved Udenyca as a biosimilar to Neulasta (pegfilgrastim, Amgen, Inc) to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia.

The approval of Udenyca was supported by a comprehensive analytical similarity package, as well as pharmacokinetic, pharmacodynamic and immunogenicity studies, including over 600 healthy subjects.

 

GAMIFANT (emapalumab)

Manufacturer: Novimmune SA

Approval Date: November 20, 2018

FDA approved Gamifant, a monoclonal antibody that binds and neutralizes interferon gamma, for adult and pediatric (newborn and older) patients with primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent or progressive disease or intolerance with conventional HLH therapy.

Approval was based on a multicenter, open-label, single-arm trial in 27 pediatric patients with suspected or confirmed primary HLH with either refractory, recurrent, or progressive disease during conventional HLH therapy or who were intolerant of conventional HLH therapy. All patients received an initial starting Gamifant dose of 1 mg/kg every 3 days. All patients received dexamethasone as background HLH treatment with doses between 5 to 10 mg/m2/day. Patients received prophylaxis for herpes zoster, Pneumocystis jirovecii, and fungal infections prior to Gamifant administration.

The ORR at the end of treatment, defined as achievement of either a complete or partial response or HLH improvement, was 63% (95% CI: 0.42, 0.81; P =.013). There were 7 complete and 8 partial responses, and 2 patients had HLH improvement, defined as ≥ 3 HLH abnormalities improved by at least 50% from baseline.

The most common adverse reactions occurring in ≥ 20% of patients were infections, hypertension, infusion-related reactions, and pyrexia. 

The recommended starting Gamifant dose is 1 mg/kg as an intravenous infusion over 1 hour twice per week. Doses subsequent to the initial dose may be increased based on clinical and laboratory criteria.

 

DAURISMO (glasdegib)

Manufacturer: Pfizer Labs

Approval Date: November 21, 2018

FDA approved Daurismo in combination with low-dose cytarabine (LDAC), for newly-diagnosed AML in patients who are 75 years old or older or who have comorbidities that preclude intensive induction chemotherapy.

Approval was based on a multicenter, open-label, randomized study (BRIGHT AML 1003) that included 115 patients with newly-diagnosed AML who met at least one of the following criteria: age 75 years or older, severe cardiac disease, baseline Eastern Cooperative Oncology Group performance status of 2, or baseline serum creatinine >1.3 mg/dL. Patients were randomized 2:1 to receive Daurismo 100 mg daily with LDAC 20 mg subcutaneously twice daily on days 1 to 10 of a 28-day cycle (N=77) or LDAC alone (N=38) in 28-day cycles until disease progression or unacceptable toxicity.

Efficacy was established based on an improvement in overall survival (date of randomization to death from any cause).  With a median follow-up of 20 months, median survival was 8.3 months (95% CI: 4.4, 12.2) for the Daurismo + LDAC arm and 4.3 months (95% CI: 1.9, 5.7) for the LDAC alone arm and HR of 0.46 (95% CI: 0.30, 0.71; P = .0002).  

The most common adverse reactions occurring in ≥ 20% of patients were anemia, fatigue, hemorrhage, febrile neutropenia, musculoskeletal pain, nausea, edema, thrombocytopenia, dyspnea, decreased appetite, dysgeusia, mucositis, constipation, and rash.

The recommended Daurismo dose is 100 mg orally, once daily. Glasdegib has not been studied in patients with the comorbidities of severe renal impairment or moderate-to-severe hepatic impairment.

 

XOSPATA (gilteritinib)

Manufacturer: Astellas Pharma

Approval Date: November 28, 2018

FDA approved Xospata tablets for the treatment of adult patients who have relapsed or refractory AML with a FLT3 mutation as detected by an FDA-approved test. The FDA also approved an expanded indication for a companion diagnostic, LeukoStrat CDx FLT3 Mutation Assay, to include use with Xospata.

The efficacy of Xospata was studied in a clinical trial of 138 patients with relapsed or refractory AML having a confirmed FLT3 mutation. Twenty-one percent of patients achieved CR (no evidence of disease and full recovery of blood counts) or CR with partial hematologic recovery (no evidence of disease and partial recovery of blood counts) with treatment. Of the 106 patients who required red blood cell or platelet transfusions at the start of treatment with Xospata, 31% became transfusion-free for at least 56 days.

Common side effects reported by patients in clinical trials were muscle and joint pain (myalgia/arthralgia), fatigue, and elevated liver enzymes (liver transaminase). Health care providers are advised to monitor patients for posterior reversible encephalopathy syndrome (a syndrome characterized by headache, confusion, seizures and visual loss), prolonged QT interval (a heart rhythm condition that can potentially cause fast, chaotic heartbeats), and pancreatitis (inflammation in the pancreas). Rare cases of differentiation syndrome (symptoms of which may include fever, cough, trouble breathing, fluid around the lungs or heart, rapid weight gain, swelling, and renal or hepatic dysfunction) have been seen in patients taking Xospata. Women who are pregnant or breastfeeding should not take Xospata because it may cause harm to a developing fetus or newborn baby.

 

TRUXIMA (rituximab-abbs)

Manufacturer: Celltrion

Approval Date: November 28, 2018

FDA approved Truxima as the first biosimilar to Rituxan (rituximab; Genentech) for the treatment of adult patients with CD20-positive, B-cell non-Hodgkin’s lymphoma (NHL) to be used as a single agent or in combination with chemotherapy.

Truxima is the first biosimiliar to be approved in the US for the treatment of NHL.

Truxima is indicated for the treatment of adult patients with:

Relapsed or refractory, low grade or follicular, CD20-positive B-cell NHL as a single agent;

Previously untreated follicular, CD20-positive, B-cell NHL in combination with first line chemotherapy and, in patients achieving a complete or partial response to a rituximab product in combination with chemotherapy, as single-agent maintenance therapy; and

Non-progressing (including stable disease), low-grade, CD20-positive, B-cell NHL as a single agent after first-line cyclophosphamide, vincristine and prednisone (CVP) chemotherapy.

The FDA’s approval of Truxima is based on a review of evidence that included extensive structural and functional characterization, animal study data, human pharmacokinetic data, clinical immunogenicity data, and other clinical data that demonstrates Truxima is biosimilar to Rituxan. Truxima has been approved as a biosimilar, not as an interchangeable product.

The most common side effects of Truxima are infusion reactions, fever, abnormally low level of lymphocytes in the blood (lymphopenia), chills, infection and weakness (asthenia). Health care providers are advised to monitor patients for tumor lysis syndrome (a complication of treatment where tumor cells are killed off at the same time and released into the bloodstream), cardiac adverse reactions, damage to kidneys (renal toxicity), and bowel obstruction and perforation. Patients should not receive vaccinations while in treatment. Women who are pregnant or breastfeeding should not take Truxima because it may cause harm to a developing fetus or newborn baby.

Like Rituxan, the labeling for Truxima contains a Boxed Warning to alert health care professionals and patients about increased risks of the following: fatal infusion reactions, severe skin and mouth reactions, some with fatal outcomes; Hepatitis B virus reactivation, that may cause serious liver problems including liver failure and death; and Progressive Multifocal Leukoencephalopathy, a rare, serious brain infection that can result in severe disability or death. This product must be dispensed with a patient Medication Guide that provides important information about the drug’s uses and risks.

 

IMMUNOLOGY

OLUMIANT (baricitinib)

Manufacturer: Eli Lilly And Co

Approval Date: May 31, 2018

FDA approved the 2-mg dose of Olumiant, a once-daily oral medication for the treatment of adults with moderately-to-severely active rheumatoid arthritis (RA) who have had an inadequate response to one or more tumor necrosis factor (TNF) inhibitor therapies. 

Olumiant may be used as monotherapy or in combination with methotrexate or other non-biologic DMARDs. Use of Olumiant in combination with other Janus kinase inhibitors or biologic disease-modifying antirheumatic drugs (bDMARDs), or with potent immunosuppressants such as azathioprine and cyclosporine is not recommended.

The Olumiant clinical trial program included the RA-BEACON study, a randomized, double-blind, placebo-controlled study in which patients were randomly assigned to receive Olumiant 2 mg, baricitinib 4 mg or placebo, in addition to conventional DMARDs that they were currently using. This study included 527 patients who had an inadequate response or intolerance to one or more TNF inhibitor therapies. Patients could have had prior therapy with other bDMARDs. The study results showed that significantly higher ACR20 response rates and improvement in all individual ACR20 component scores were observed at Week 12 with Olumiant. Olumiant also demonstrated early symptom relief, with ACR20 responses seen as early as Week 1. Patients treated with Olumiant reported significant improvements in physical function based on the Health Assessment Questionnaire Disability Index (HAQ-DI) (recording an average score of 1.71 before treatment and 1.31 at Week 12) compared to placebo-treated patients (who recorded an average score of 1.78 before treatment and 1.59 at Week 12).

The most common adverse events (occurring in greater than or equal to 1% of Olumiant 2 mg- and baricitinib 4 mg-treated patients in placebo-controlled trials) included upper respiratory tract infections, nausea, herpes simplex and herpes zoster. Serious infections leading to hospitalization or death, including tuberculosis and bacterial, invasive fungal, viral, and other opportunistic infections, have occurred in patients receiving Olumiant. Lymphoma and other malignancies have been observed in patients treated with Olumiant as well. Additionally, thrombosis, including deep venous thrombosis, pulmonary embolism and arterial thrombosis, some fatal, have occurred in patients treated with Olumiant. Other warnings and precautions include gastrointestinal perforations, laboratory abnormalities (including neutropenia, lymphopenia, anemia, liver enzyme elevations, and lipid elevations) and a warning against the use of live vaccines with Olumiant. 

 

HYRIMOZ (adalimumab-adaz)

Manufacturer: Sandoz Inc

Approval Date: October 30, 2018

FDA approved Hyrimoz as a biosimilar to Humira (adalimumab; Abbvie) for the treatment of rheumatoid arthritis (RA), juvenile idiopathic arthritis in patients four years of age and older, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, ulcerative colitis, and plaque psoriasis.

The FDA approval of Hyrimoz was based on a comprehensive data package comprising analytical, preclinical and clinical research demonstrating that Hyrimoz matches the reference biologic in terms of safety, efficacy and quality. A randomized, double-blind, three-arm, parallel biosimilarity study confirmed the pharmacokinetics, immunogenicity and safety of Hyrimoz. The study met the primary endpoint, demonstrating bioequivalence for all primary pharmacokinetic parameters. A confirmatory efficacy and safety biosimilarity study (ADACCESS) demonstrated therapeutic equivalence in the sensitive indication of patients with moderate to severe chronic plaque-type psoriasis, with a similar safety and immunogenicity profile to the reference biologic.

 

FIRDAPSE (amifampridine)

Manufacturer: Catalyst Pharmaceuticals Inc

Approval Date: November 28, 2018

FDA approved Firdapse tablets for the treatment of Lambert-Eaton myasthenic syndrome (LEMS) in adults. LEMS is a rare autoimmune disorder that affects the connection between nerves and muscles and causes weakness and other symptoms in affected patients. This is the first FDA approval of a treatment for LEMS.

The efficacy of Firdapse was studied in two clinical trials that together included 64 adult patients who received Firdapse or placebo. The studies measured the Quantitative Myasthenia Gravis score (a 13-item physician-rated categorical scale assessing muscle weakness) and the Subject Global Impression (a seven-point scale on which patients rated their overall impression of the effects of the study treatment on their physical well-being). For both measures, the patients receiving Firdapse experienced a greater benefit than those on placebo.

The most common side effects experienced by patients in the clinical trials were burning or prickling sensation (paresthesia), upper respiratory tract infection, abdominal pain, nausea, diarrhea, headache, elevated liver enzymes, back pain, hypertension and muscle spasms. Seizures have been observed in patients without a history of seizures. Patients should inform their health care provider immediately if they have signs of hypersensitivity reactions such as rash, hives, itching, fever, swelling or trouble breathing.