New FDA Drug Approvals in 2020 by Indication: Part 2

This special section of First Report Managed Care includes data on the new molecular entities and new therapeutic biological products approved by the US Food & Drug Administration’s Center for Drug Evaluation and Research in 2020. Per the FDA website, “Some of these products are innovative new products that never have been used in clinical practice…This listing does not contain vaccines, allergenic products, blood and blood products, plasma derivatives, cellular and gene therapy products, or other products approved in 2020 by the Center for Biologics Evaluation and Research.” All data from this section has been taken directly from the FDA.

This part 2 page includes approvals in oncology, ophthalmology, pain management, and procedural medicine. You can find approval listings for dermatology, endocrinology, gastroenterology, genetic diseases, hematology, infectious diseases, and neurology in part 1 here.

ONCOLOGY

AYVAKIT (avapritinib)
Manufacturer: Blueprint Medicines Corporation
Approval Date: January 9, 2020

FDA approved Ayvakit to treat adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) caused by specific PDGFRA sequence variations that cannot be surgically removed or is metastatic.s

The approval for Ayvakit was based upon the NAVIGATOR clinical trial analyzing 204 patients with GIST. Patients with unresectable or metastatic GIST and sequence variations on the PDGFRA exon 18 (including D842V) received avapritinib once daily until disease progression or unacceptable toxicity. The benefit of avapritinib was measured by the percentage of patients experiencing partial or complete shrinkage of the tumor, as well as duration of the shrinkage.

Of the patients, 84% (95% CI, 69%-93%) had complete or partial tumor shrinkage; complete response accounted for 7%, and partial response accounted for 77%. In 61% of these patients (22 persons), shrinkage lasted greater than 6 months.

Adverse effects of Ayvakit include swelling, nausea, tiredness, trouble thinking, vomiting, decreased appetite, diarrhea, hair color change, increase tear secretions, abdominal pain, constipation, rash, and dizziness.

Avapritinib is an oral tablet, taken once daily on an empty stomach.

DANYELZA (naxitamab-gqgk)
Manufacturer: Y-mAbs Therapeutics, Inc
Approval Date: November 25, 2020

FDA approved Danyelza to treat high-risk refractory or relapsed neuroblastoma for pediatric patients aged 1 year and older and adult patients who have demonstrated a partial response, minor response, or stable disease to prior therapy.

The safety of Danyelza in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF) was evaluated in patients with refractory or relapsed high-risk neuroblastoma in bone or bone marrow who had demonstrated a partial response, minor response, or stable disease following initial or subsequent therapy, and in patients who were in second complete remission, from two open-label, single-arm studies, Study 201 (n=25) and Study 12-230 (n=72). Patients received Danyelza 9 mg/kg/cycle administered as three separate intravenous infusions of 3 mg/kg (Day 1, 3, and 5) in the first week of each cycle. Patients also received GM-CSF 250 µg/m2 /day subcutaneously on Days -4 to 0 and GM-CSF 500 µg/m2 /daysubcutaneously on Days 1 to 5.

The most commonly observed adverse reactions were infusion-related reaction, pain, tachycardia, vomiting, cough, nausea, diarrhea, decreased appetite, hypertension, fatigue, erythema multiforme, peripheral neuropathy, urticaria, pyrexia, headache, injection site reaction, edema, anxiety, localized edema, and irritability.

The recommended dosage of Danyelza is 3 mg/kg/day (up to 150 mg/day), administered as an intravenous infusion after dilution on Days 1, 3, and 5 of each treatment cycle. Treatment cycles are repeated every 4 weeks until complete response or partial response, followed by five additional cycles every 4 weeks. Subsequent cycles may be repeated every 8 weeks.

GAVRETO (pralsetinib)
Manufacturer: Blueprint Medicines
Approval Date: September 4, 2020

FDA approved Gavreto to treat non-small lung cancer (NSCLC) that is caused by abnormal RET genes.

The approval of Gavreto was based on evidence from a clinical trial composed of 220 patients aged 26 to 87 years who had NSCLC caused by abnormal RET genes. Some patients had previously been treated for metastatic NSCLC and others were treatment naive. All patients received Gavreto orally once daily until cancer progression or intolerable adverse effects. The benefits were measured by the overall response rate of patients achieving complete or partial tumor shrinkage and by duration of response. In patients with previously treated NSCLC, 57% (95% CI, 46%-68%) of the 87 patients experienced complete or partial tumor shrinkage. For 80% of patients, shrinkage lasted greater than 6 months. In patients who had never received treatment (27 total), 70% (95% CI, 50%-86%) had complete or partial tumor shrinkage. For 58% of patients, shrinkage lasted greater than 6 months.

The most common adverse reactions reported for Gavreto are tiredness, constipation, joint and muscle pain, and increased blood pressure. The most common laboratory abnormalities are increased liver enzymes, increased creatinine, and decreased blood cell counts.

The recommended dose of Gavreto, an oral capsule, is 400 mg (4 capsules) taken once daily on an empty stomach.

MONJUVI (tafasitamab-cxix)
Manufacturer: MorphoSys US Inc
Approval Date: July 31, 2020

FDA approved Monjuvi to treat adults with diffuse large B-cell lymphoma (DLBCL) whose disease has returned or has not improved after previous treatments. It is to be used when patients cannot receive a stem cell transplant.

The approval of Monjuvi is based primarily on evidence from one clinical trial of 81 patients aged 42 to 86 years. In the clinical trial, of 71 patients with DLBCL assigned to receive Monjuvi plus lenalidomide, 55% had complete or partial shrinkage of their tumors that lasted about 22 months. Patients who participated in the trial had lymphoma that returned or did not improve after prior treatments. 

The most common side effects of Monjuvi are low blood cell counts, fatigue, diarrhea, cough, fever, limb swelling, upper respiratory infection, and decreased appetite. More serious side effects include infusion-related reactions, bone marrow suppression, infections, and harm to an unborn baby.

The recommended dose of Monjuvi is 12 mg/kg based on body weight administered as an intravenous infusion on a 28-day treatment cycle. 

PEMAZYRE (pemigatinib)
Manufacturer: Incyte
Approval Date: April 17, 2020

FDA approved Pemazyre to treat certain patients with cholangiocarcinoma, a rare form of cancer that forms in bile ducts.

The approval of Pemazyre was based on results of a clinical trial that enrolled 107 patients with locally advanced or metastatic cholangiocarcinoma with an FGFR2 fusion or rearrangement who had received prior treatment. During the clinical trial, patients received Pemazyre once daily for 14 consecutive days, followed by 7 days off, in 21-day cycles until the disease progression or the patient experienced an unreasonable level of side effects. To assess how well Pemazyre was working during the trial, patients were scanned every 8 weeks. The trial used established criteria to measure how many patients experienced a complete or partial shrinkage of their tumors during treatment (overall response rate). The overall response rate was 36%, with 2.8% of patients having a complete response and 33% having a partial response. Among the 38 patients who had a response, 24 patients (63%) had a response lasting 6 months or longer and 7 patients (18%) had a response lasting 12 months or longer.

The most commonly observed side effects of Pemazyre include hyperphosphatemia and hypophosphatemia, alopecia, diarrhea, nail toxicity, fatigue, dysgeusia, nausea, constipation, stomatitis, dry eye, dry mouth, decreased appetite, vomiting, joint pain, abdominal pain, back pain and dry skin.

The recommended dosage of Pemazyre is 13.5 mg orally once daily for 14 consecutive days followed by 7 days off therapy, in 21-day cycles.

QINLOCK (ripretinib)
Manufacturer: Deciphera Pharmaceuticals, Inc.
Approval Date: May 15, 2020

FDA approved Qinlock to treat advanced gastrointestinal-stromal tumors.

Qinlock’s approval was based on the results of an international, multi-center, randomized, double-blind, placebo-controlled clinical trial that enrolled 129 patients with advanced GIST who had received prior treatment with other FDA-approved targeted therapies, imatinib, sunitinib and regorafenib. The trial compared patients who were randomized to receive Qinlock to patients who were randomized to receive placebo, to determine whether progression free survival (PFS)—the time from initial treatment in the clinical trial to growth of the cancer or death—was longer in the Qinlock group compared to the placebo group. During treatment in the trial, patients received Qinlock or placebo once a day in 28-day cycles, repeated until tumor growth was found (disease progression), or the patient experienced intolerable side effects. After disease progression, patients who were randomized to placebo were given the option of switching to Qinlock.

The most common side effects with Qinlock were alopecia (hair loss), fatigue, nausea, abdominal pain, constipation, myalgia (muscle pain), diarrhea, decreased appetite, palmar-plantar erythrodysesthesia syndrome (a skin reaction in the palms and soles) and vomiting.

Qinlock is a tablet taken once daily.

RETEVMO (selpercatinib)
Manufacturer: Eli Lilly
Approval Date: May 8, 2020

FDA approved Retevmo to treat lung and thyroid cancers in patients whose tumors have an alteration (mutation or fusion) in a specific gene. 

The FDA granted approval of selpercatinib under the accelerated approval program based on evidence from a trial of 702 patients aged 15 to 92 years, with certain cancers caused by abnormal RET genes. This trial included patients with non–small-cell lung cancer (NSCLC), medullary thyroid cancer, and thyroid cancer. Some patients had received previous treatments while others were treatment naive. All patients received Retevmo orally twice daily until cancer progression or intolerable adverse effects. The benefit was measured by ORR (percent of patients with tumor shrinkage) and DOR. Of the 105 patients with previously treated NSCLC, 64% experienced complete or partial tumor shrinkage (95% CI, 54%-73%), 81% of whom experienced this for a duration greater than 6 months. Of the 39 patients who were treatment naive, 85% (95% CI, 7%-94%) experienced tumor shrinkage, with 58% of those patients experiencing shrinkage that lasted greater than 6 months.

The most common side effects with Retevmo were increased aspartate aminotransferase and alanine aminotransferase enzymes in the liver, increased blood sugar, decreased white blood cell count, decreased albumin in the blood, decreased calcium in the blood, dry mouth, diarrhea, increased creatinine, increased alkaline phosphatase, hypertension, fatigue, swelling in the body or limbs, low blood platelet count, increased cholesterol, rash, constipation, and decreased sodium in the blood.

Retevmo is a capsule taken orally twice a day.

SARCLISA (isatuximab)
Manufacturer: Sanofi
Approval Date: March 2, 2020

FDA approved Sarclisa in combination with pomalidomide and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor.

The approval for Sarclisa was based on the results of a clinical trial involving 307 patients with relapsed and refractory multiple myeloma who had received at least two prior therapies, including lenalidomide and a proteasome inhibitor. Half of the patients received Sarclisa in combination with pomalidomide and low-dose dexamethasone and the other half received only pomalidomide and low-dose dexamethasone. Patients who received Sarclisa in combination with pomalidomide and low-dose dexamethasone showed improvement in progression-free survival with a 40% reduction in the risk of disease progression or death compared to patients who received pomalidomide and dexamethasone. These patients also had an overall response rate of 60.4%. 

The most common side effects observed are neutropenia, infusion-related reactions, pneumonia, upper respiratory tract infection, diarrhea, anemia, lymphopenia, and thrombocytopenia. Sarclisa can cause severe side effects including intravenous infusion-related reactions.

Sarclisa is administered by a health care professional intravenously every week for 4 weeks, followed by every 2 weeks.

TABRECTA (capmatinib)
Manufacturer: Novartis
Approval Date: May 6, 2020

FDA approved Tabrecta to treat patients with non-small cell lung cancer (NSCLC).

The approval of Tabrecta was based on the GEOMETRY clinical trial of 334 patients with metastatic NSCLC with MET mutation. Some patients had received previous treatment, and others were treatment naive. Patients received 400 mg of Tabrecta twice daily until cancer progression or intolerable adverse effects. The benefit was measured by overall response rate (ORR) through tumor shrinkage and by duration of response (DOR).

Of the 28 patients who were treatment naive, 68% (95% CI, 48-84) experienced complete or partial tumor shrinkage with a treatment duration of 12.6 months (95% CI, 5.5-25.3). Of the 69 patients who had received previous treatment, the ORR was 41% (95% CI, 29-53) with a DOR of 9.7 months (95% CI, 5.5-13.0).

The most common adverse effects of Tabrecta are swelling of the hands and feet, nausea, tiredness, vomiting, dyspnea, and decreased appetite.

Tabrecta is an oral capsule, taken twice daily.

TAZVERIK (tazemetostat)
Manufacturer: Epizyme
Approval Date: January 23, 2020

FDA approved Tazverik to treat epithelioid sarcoma in patients aged 16 years or older. 

The approval of Tazverik was based on the results of a clinical trial enrolling 62 patients with metastatic or locally advanced epithelioid sarcoma in which patients received 800 mg of Tazverik twice a day until the disease progression or unacceptable level of toxicity. Tumor response assessments were performed every 8 weeks. The trial measured how many patients experienced complete or partial shrinkage (by a certain amount) of their tumors during treatment (overall response rate). The overall response rate was 15%, with 1.6% of patients having a complete response and 13% having a partial response. Of the nine patients who had a response, six (67%) patients had a response lasting 6 months or longer.

The most common side effects were pain, fatigue, nausea, decreased appetite, vomiting, and constipation. Serious adverse effects of Tazverik are development of other cancers and fetal harm. 

Recommended dosage of Tazverik is four tablets (800 mg) taken orally twice daily.

TRODELVY (sacituzumab govitecan-hziy)
Manufacturer: Immunomedics
Approval Date: April 22, 2020

FDA approved Trodelvy to treat adult patients with metastatic triple-negative breast cancer who received at least two prior therapies for metastatic disease.

The approval was granted based on results from the multicenter IMMU-132-01 trial of 108 patients. The primary efficacy outcome measures were investigator assessed overall response rate (ORR) using RECIST 1.1 and response duration. The ORR was 33.3% (95% CI: 24.6, 43.1). The median response duration was 7.7 months (95% CI: 4.9, 10.8).

The most common adverse effects of Trodelvy were nausea, neutropenia, diarrhea, fatigue, anemia, vomiting, hair loss, constipation, rash, decreased appetite, and abdominal pain.

Trodelvy’s recommended dose is 10 mg/kg administered via intravenous infusion by a health care provider once weekly on days 1 and 8 of 21-day treatment cycles.

TUKYSA (tucatinib)
Manufacturer: Seattle Genetics
Approval Date: April 17, 2020

FDA approved Tukysa to treat patients with advanced unresectable or metastatic HER2-positive breast cancer.

The approval of Tukysa was granted based on data from the HER2CLIMB trial of 601 patients who had previously received treatment. Patients received tucatinib or placebo twice daily, in combination with trastuzumab and capecitabine. Treatment continued until the disease progression or adverse effects were too toxic. Progression-free survival measured in patients taking Tukysa was 7.8 months (95% CI, 7.5-9.6) compared with 5.6 months (95% CI, 4.2-7.1) in patients receiving placebo (hazard ratio, 0.54; 95% CI, 0.42-0.71; P<.00001).

Tukysa may cause serious adverse effects, including severe diarrhea, liver damage, and fetal harm. The most common adverse effects were diarrhea, palmar-plantar erythrodysesthesia, nausea, tiredness, liver toxicity, vomiting, and mouth sores.

Tukysa is administered orally twice daily in combination with trastuzumab and capecitabine.

ZEPZELCA (lurbinectedin)
Manufacturer: PharmaMar
Approval Date: June 15, 2020

FDA approved Zepzelca to treat metastatic small cell lung cancer.

The approval for Zepzelca was based on evidence from the RECIST clinical trial consisting of 105 adults with metastatic small-cell lung cancer (SCLC). All patients had SCLC that had progressed on or after previous platinum-based therapy and received Zepzelca infusions once every 3 weeks until tumor progression or intolerable adverse effects. The benefit was measured in the overall response rate (ORR), percent of patients achieving complete or partial tumor shrinkage, and by measuring duration of response (DOR). Of the 105 patients with SCLC receiving Zepzelca, 35% (95% CI, 26%-45%) experienced partial tumor shrinkage, with a median DOR of 5.3 months (95% CI, 4.1-6.4). The ORR was 30% (95% CI, 22%-40%) with a median DOR of 5.1 months (95% CI, 4.9-6.4).

The most common adverse effects are decreased blood cell counts, tiredness, increased creatinine, alanine transaminase, blood glucose, and nausea.

Zepzelca is administered intravenously by a health care provider every 3 weeks over a 1-hour infusion period.

OPHTHALMOLOGY

TEPEZZA (teprotumumab-trbw)
Manufacturer: Horizon
Approval Date: January 21, 2020

FDA approved Tepezza for the treatment of adults with thyroid eye disease, a rare condition where the muscles and fatty tissues behind the eye become inflamed, causing the eyes to be pushed forward and bulge outward.

The approval of Tepezza was based on results of two studies consisting of a total of 170 patients with active thyroid eye disease who were randomized to either receive Tepezza or a placebo. Of the patients who were administered Tepezza, 71% in Study 1 and 83% in Study 2 demonstrated a greater than 2-mm reduction in proptosis (eye protrusion) as compared to 20% and 10% of participants who received placebo, respectively.

The most common adverse effects include muscle spasm, nausea, alopecia, diarrhea, fatigue, hyperglycemia, hearing loss, dry skin, dysgeusia, and headache. Tepezza should not be used if pregnant, and women of child-bearing potential should have their pregnancy status verified prior to beginning treatment and should be counseled on pregnancy prevention during treatment and for 6 months following the last dose.

Tepezza is administered once every 3 weeks for a total of eight infusions. The initial dose for Tepezza is 10 mg/kg. Doses 2 to 8 increase to 20 mg/kg.  

PAIN MANAGEMENT

OLINVYK (oliceridine)
Manufacturer: Trevena, Inc
Approval Date: August 7, 2020

FDA approved Olinvyk, an opioid agonist, for the management of moderate to severe acute pain in adults, where the pain is severe enough to require an intravenous opioid and for whom alternative treatments are inadequate.

The approval of Olinvyk is based on safety and efficacy data established by comparing Olinvyk to placebo in randomized, controlled studies of patients who had undergone bunion surgery or abdominal surgery. Patients administered Olinvyk reported decreased pain compared to placebo at the approved doses.

The safety profile of Olinvyk is similar to other opioids. As with other opioids, the most common side effects of Olinvyk are nausea, vomiting, dizziness, headache and constipation. Olinvyk should not be given to patients with significant respiratory depression; acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment; known or suspected gastrointestinal obstruction; or known hypersensitivity to the drug. Prolonged use of opioid analgesics during pregnancy can result in neonatal opioid withdrawal syndrome.

Olinvyk is administered intravenously by a health care provider with a maximum dosage of 27 mg per day. 

PROCEDURAL MEDICINE

BARHEMSYS (amisulpride)
Manufacturer: Acacia Pharma
Approval Date: February 26, 2020

FDA approved Barhemsys for the prevention of postoperative nausea and vomiting (PONV), either alone or in combination with an antiemetic of a different class, and the treatment of PONV in patients who have received antiemetic prophylaxis with an agent of a different class or have not received prophylaxis.

The approval of Barhemsys was based on a randomized, double-blind, placebo-controlled study involving patients who had failed the
most commonly used antiemetic prophylaxis, a single 10-mg dose
(n=230) was significantly more effective than placebo (n=235) at treating patients (42% vs 29%; P=.003). In a double-blind, randomized, placebo-controlled study in patients at the highest risk of suffering from PONV (Apfel score 3 or 4), a single 5-mg dose of Barhemsys in combination with another antiemetic (n=572) significantly improved protection from PONV compared to placebo plus another antiemetic (n=575; 58% vs 47%; P<.001).

The most common side effects observed were infusion site pain, chills, hypokalemia, procedural hypotension, and abdominal distension.

For the prevention of PONV the recommended adult dosage is 5 mg as a single intravenous injection infused over 1 to 2 minutes at the time of induction of anesthesia. For the treatment of PONV, 10 mg as a single intravenous injection infused over 1 to 2 minutes in the event of nausea and/or vomiting after a surgical procedure.

BYFAVO (remimazolam)
Manufacturer: Acacia Pharma
Approval Date: July 2, 2020

FDA approved Byfavo for the induction and maintenance of procedural sedation in adults undergoing procedures lasting 30 minutes or less. 

The approval of Byfavo was based on efficacy and safety data from three multicenter, randomized, double-blind, phase 3 studies in which Byfavo was compared with a saline placebo with a midazolam rescue treatment group and an open-label midazolam treatment group in 969 adult patients undergoing colonoscopy or bronchoscopy procedure. Patients who received Byfavo for sedation during scheduled colonoscopy responded at a numerically greater rate than patients who received placebo (randomized analysis population (27/32 [84.4%]; placebo: 5/16 [15.6%]).

The most common adverse reactions reported with Byfavo included hypotension, hypertension, diastolic hypertension, systolic hypertension, hypoxia, and diastolic hypotension.

Byfavo will be supplied as 20-mg single-use vials and for adult patients, dosage is recommended at 5 mg intravenously over 1 minute.

Find approval listings for dermatology, endocrinology, gastroenterology, genetic diseases, hematology, infectious diseases, and neurology in part 1 here.