You are here

New Drugs/Drug News

Drug and Device News October 2018

NEW DRUG APPROVALS

Delstrigo, Pifeltro For HIV-1 Infection

The FDA has approved two new human immunodeficiency virus-1 (HIV-1) medications from Merck. Delstrigo is a once-daily, fixed-dose combination tablet of doravirine (DOR, 100 mg), lamivudine (3TC, 300 mg) and tenofovir disoproxil fumarate (TDF, 300 mg). Pifeltro (DOR, 100 mg) is a non-nucleoside reverse transcriptase inhibitor to be administered in combination with other antiretroviral medicines.

Both medications are indicated for the treatment of HIV-1 infection in adults with no prior antiretroviral treatment experience. They are administered orally once daily with or without food.

The approvals are based on pivotal, randomized, multicenter, double-blind, active controlled phase 3 trials in participants with HIV-1 and no antiretroviral treatment history.

Source: Merck, August 30, 2018

Jivi for Hemophilia A

The FDA has approved antihemophilic factor (recombinant) PEGylated-aucl (Jivi, Bayer) for the routine prophylactic treatment of hemophilia A in previously treated adults and adolescents 12 years of age or older.

Jivi’s initial recommended dosing regimen is twice weekly (30–40 IU/kg) with the ability to dose every five days (45–60 IU/kg) and further adjust the frequency of dosing based on bleeding episodes. The FDA also approved Jivi for on-demand treatment and the peri-operative management of bleeding in the same population. This approval is based on results from the 36-week phase 2/3 PROTECT VIII trial, which demonstrated bleeding protection and safety of up to a median of 1.9 years (range, 0–2.6 years).

Jivi works by replacing the reduced or missing factor VIII in adults and adolescents 12 years of age or older with hemophilia A.

Treatment with Jivi was well tolerated in the majority of patients in clinical trials.

Source: Bayer, August 31, 2018

Diacomit for Seizures From Dravet Syndrome

Stiripentol (Diacomit, Biocodex SA) has secured FDA approval for the treatment of seizures associated with Dravet syndrome (DS) in patients 2 years of age and older taking clobazam. It is available in capsules and powder for oral suspension.

The approval was based on two multicenter, placebo-controlled trials, STICLO France and STICLO Italy. The primary efficacy endpoint was the responder rate, with a responder defined as a patient who experienced a greater than 50% decrease in the 30-day frequency of generalized clonic or tonic-clonic seizures during the double-blind treatment period compared to the four-week baseline period.

The most common adverse reactions included somnolence (67%), decreased appetite (45%), agitation (27%), ataxia (27%), weight decrease (27%), hypotonia (24%), nausea (15%), tremor (15%), dysarthria (12%), and insomnia (12%).

Dravet syndrome, also known as severe myoclonic epilepsy in infancy, is a catastrophic early-onset epileptic syndrome that is thought to affect approximately 2,000 to 8,000 U.S. patients.

Biocodex received an FDA orphan drug designation for stiripentol.

Source: Biocodex, August 23, 2018

Oxervate for Neurotrophic Keratitis

The FDA has approved cenegermin (Oxervate, Dompé farmaceutici SpA), a topical eye drop that is the first drug for the treatment of neurotrophic keratitis. This rare degenerative disease results from a loss of corneal sensation, which impairs corneal health and causes progressive damage to the top layer of the cornea. The prevalence of neurotrophic keratitis has been estimated at less than five in 10,000 individuals.

The safety and efficacy of cenegermin were studied in 151 patients with neurotrophic keratitis in two eight-week, randomized, controlled, multicenter, double-blinded studies. Eye drops in both studies were given six times daily. Across both studies, complete corneal healing in eight weeks was demonstrated in 70% of patients treated with cenegermin compared to 28% of patients treated without cenegermin.

The most common adverse reactions in patients taking cenegermin are eye pain, ocular hyperemia, eye inflammation, and increased lacrimation.

Oxervate was granted an orphan drug designation.

Source: FDA, August 22, 2018

Galafold for Fabry Disease

The FDA has approved migalastat (Galafold, Amicus Therapeutics) as the first oral medication for the treatment of adults with Fabry disease. The drug is indicated for adults who have a genetic mutation determined to be responsive to migalastat based on laboratory data.

Fabry disease is a rare, inherited disorder caused by mutations in the alpha-galactosidase A (GLA) gene located on the X-chromosome; it results from the buildup of globotriaosylceramide (GL-3) in blood vessels, nerves, and organs, leading to slowly progressive kidney disease, cardiac hypertrophy, arrhythmias, stroke, and early death. While other Fabry treatments have involved replacing the missing enzyme that causes the fat buildup in this disease, migalastat increases the activity of the body’s deficient enzyme.

In a six-month, placebo-controlled trial in 45 adults with Fabry disease, patients treated with migalastat had a greater reduction in GL-3 in blood vessels of the kidneys (as measured in kidney biopsy samples) compared with patients taking placebo. Migalastat’s safety was studied in four clinical trials that included 139 patients with Fabry disease; the most common adverse drug reactions in migalastat patients were headache, nasopharyngitis, urinary tract infection, nausea, and pyrexia.

Galafold was granted priority review and orphan drug designations.

Source: FDA, August 10, 2018

Onpattro for Polyneuropathy

Patisiran infusion (Onpattro, Alnylam Pharmaceuticals) has received the first FDA approval for the treatment of adults with polyneuropathy caused by hereditary transthyretin-mediated amyloidosis (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. This is also the first FDA approval in a new class of drugs called small interfering ribonucleic acid (siRNA) treatment, which works by silencing a portion of RNA involved in causing the disease.

Patisiran’s efficacy was shown in a clinical trial involving 225 patients. Once every three weeks for 18 months, 148 patients received a patisiran infusion and 77 received placebo. Patients who received patisiran had better outcomes on measures of polyneuropathy including muscle strength, sensation, reflexes, and autonomic symptoms than did those receiving placebo. Patisiran-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 with patisiran are infusion-related, including flushing, back pain, nausea, abdominal pain, dyspnea, and headache. All patients in the trials were premedicated with a corticosteroid, acetaminophen, and antihistamines to reduce infusion-related reactions. Patients may also experience vision problems. Patisiran leads to a decrease in vitamin A levels, so patients should take a vitamin A supplement.

The FDA granted this application fast track, priority review, breakthrough therapy, and orphan drug designations.

Source: FDA, August 10, 2018

Annovera Yearly Birth Control

The FDA has approved the segester-one acetate/ethinyl estradiol vaginal system (Annovera, The Population Council), a combined hormonal contraceptive for women of reproductive age. It is the first vaginal ring contraceptive that can be used for an entire year.

The efficacy and safety of Annovera were studied in three open-label clinical trials with healthy women ranging from 18 to 40 years of age. Based on the results, about two to four women out of 100 may get pregnant during the first year they use Annovera.

Annovera carries a boxed warning relating to cigarette smoking and serious cardiovascular events: Women older than 35 years of age who smoke should not use it. The product is contraindicated in women with a high risk of arterial or venous thrombotic diseases; current or past breast cancer or other estrogen- or progestin-sensitive cancer; liver tumors, acute hepatitis, or decompensated cirrhosis; undiagnosed abnormal uterine bleeding; hypersensitivity to any of Annovera’s components; and use of hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir.

The most common side effects with Annovera include headache/migraine, nausea/vomiting, yeast infections, abdominal pain, dysmenorrhea, breast tenderness, irregular bleeding, diarrhea, and genital itching.

The FDA is requiring post-marketing studies to further evaluate the risks of venous thromboembolism and the effects of cytochrome P450 3A modulating drugs and tampon use on the pharmacokinetics of Annovera.

Source: FDA, August 10, 2018

Poteligeo for Mycosis Fungoides and Sézary Syndrome

The FDA has approved mogamulizumab-kpkc injection (Poteligeo, Kyowa Kirin, Inc.) for intravenous use in treating adults with relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS) after at least one prior systemic therapy. MF and SS are rare, hard-to-treat types of non-Hodgkin’s lymphoma in which lymphocytes become cancerous and affect the skin.

Poteligeo is a monoclonal antibody that binds to the protein CC chemokine receptor type 4 (CCR4) found on some cancer cells. Its approval was based on a clinical trial of 372 patients with relapsed MF or SS who received either mogamulizumab or vorinostat chemotherapy. Progression-free survival was longer with mogamulizumab (median, 7.6 months) than vorinostat (median, 3.1 months). The most common side effects of mogamulizumab included rash, infusion-related reactions, fatigue, diarrhea, musculoskeletal pain, and upper respiratory tract infection.

Serious warnings about treatment with mogamulizumab include the risk of dermatologic toxicity, infusion reactions, infections, autoimmune problems, and complications with allogeneic stem-cell transplantation.

The FDA granted this application priority review, breakthrough therapy, and orphan drug designations.

Source: FDA, August 8, 2018

Mulpleta for Thrombocytopenia

Lusutrombopag (Mulpleta, Shionogi & Co., Ltd.) has won FDA approval as a once-daily, orally administered, small-molecule thrombopoietin (TPO) receptor agonist for the treatment of thrombocytopenia in adults with chronic liver disease who are scheduled to undergo a procedure.

The approval was based on consistent safety and efficacy data from two phase 3 clinical trials, L-PLUS 1 and L-PLUS 2. The most common adverse reaction with lusutrombopag was headache.

Thrombocytopenia is a common complication of chronic liver disease, which may be caused by multiple factors, including decreased production of TPO.

Mulpleta received an FDA priority review.

Source: Shionogi, August 1, 2018

Krintafel, Arakoda to Treat, Prevent Malaria

The FDA has approved two tafenoquine-based medications to treat and prevent malaria.

As single-dose Krintafel (GlaxoSmith-Kline and Medicines for Malaria Venture), tafenoquine is to be given for the radical cure (prevention of relapse) of Plasmodium vivax malaria in patients who are 16 years of age and older and who are receiving appropriate antimalarial therapy for acute P. vivax infection. It is the first new treatment for P. vivax malaria in more than 60 years.

As Arakoda (60 Degrees Pharmaceuticals [60P]), tafenoquine is indicated for the prevention of malaria in patients who are 18 years of age and older—the first FDA approval of a drug to prevent malaria in 18 years.

Tafenoquine was synthesized by scientists at the Walter Reed Army Institute of Research in 1978. The Arakoda approval was based on a concerted effort by the U.S. Army and 60P, involving more than 21 clinical trials and over 3,100 trial subjects, to develop tafenoquine as a weekly prophylactic drug for the prevention of malaria.

Arakoda provides effective protection against both major types of malaria (P. vivax and P. falciparum). It is supplied in 100-mg tablets for oral use only. After an initial loading dose prior to travel, Arakoda is intended to be taken once a week; 60P has committed to performing post-marketing safety surveillance studies.

The most common adverse reactions (5% or more) observed for Krintafel in clinical trials were dizziness, nausea, vomiting, headache, and decreased hemoglobin. The most common adverse reactions to Arakoda in trials (1% or more) were headache, dizziness, back pain, diarrhea, nausea, vomiting, increased alanine aminotransferase, motion sickness, insomnia, depression, abnormal dreams, and anxiety.

Tafenoquine is an 8-aminoquinoline chemically derived from primaquine.

Sources: GlaxoSmithKline, July 20, 2018; 60 Degrees Pharmaceuticals, August 9, 2018

Tecovirimat for Smallpox

The FDA has approved tecovirimat (TPOXX, SIGA Technologies Inc.) to treat smallpox.

Although the World Health Organization declared smallpox to be eradicated in 1980, antiterrorism experts worry that radical groups could use the disease to wipe out populations who may never have been inoculated against it. The new treatment offers an additional option if smallpox is ever used as a bioweapon.

Tecovirimat is the first FDA-approved drug with an indication for treating smallpox. The FDA had granted tecovirimat fast track, priority review, and orphan drug designations. It was also awarded a material threat medical countermeasure priority review voucher.

Source: FDA, July 13, 2018

Generic Approvals

First Generic EpiPen

The FDA has approved the first generic version of the EpiPen and EpiPen Jr. auto-injector for the emergency treatment of allergic reactions, including anaphylaxis, in adults and pediatric patients who weigh more than 33 pounds. The generic epinephrine auto-injector (Teva) is available in 0.3-mg and 0.15-mg strengths.

The EpiPen automatically injects a dose of epinephrine into a person’s thigh to stop an allergic reaction. The FDA has approved several epinephrine auto-injector products under new drug applications to treat anaphylaxis, including EpiPen, Adrenaclick, and Auvi-Q. Some hope that the new generic approval will lead to a price reduction for Mylan’s costly EpiPen, which dominates the market. Between 2009 and 2016, Mylan raised the price of the device more than 500%.

Sources: FDA, August 16, 2018; Modern Healthcare, August 20, 2018

Potassium Chloride Oral Solution

The FDA has approved the marketing of potassium chloride oral solution USP, 10% (20 mEq/15 mL) and 20% (40 mEq/15 mL) by Apotex Inc.—the first generic drugs to receive a competitive generic therapy (CGT) designation. This new approval pathway was created to expedite the development of a generic drug for products that lack competition.

Potassium chloride is indicated for the treatment and prevention of hypokalemia in patients who are on diuretics, and when dietary management with potassium-rich foods is insufficient or diuretic dose reduction is not possible.

Source: FDA, August 8, 2018

Temsirolimus Injection

The FDA has approved Accord Healthcare’s production of temsirolimus injection, 25 mg/mL single-dose vial. Temsirolimus is the generic form of Torisel Injection, 25 mg/mL (PF Prism CV), used in the treatment of advanced renal-cell carcinoma.

Source: FDA, July 30, 2018

Teriflunomide Tablets

Watson Laboratories has been granted FDA permission to market 7-mg and 14-mg teriflunomide tablets, the generic version of Aubagio (Sanofi Aventis US). Teriflunomide is a treatment for patients with relapsing forms of multiple sclerosis.

Source: FDA, July 27, 2018

Dorzolamide Hydrochloride/Timolol Maleate Ophthalmic Solution

Aurobindo Pharma has received FDA approval to market dorzolamide hydrochloride and timolol maleate ophthalmic solution, 2% / 0.5% PF, for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension who do not respond to beta blockers. The drug is the generic form of Cosopt Ophthalmic Solution, 2% / 0.5% PF (Oak Pharmaceuticals).

Source: FDA, July 24, 2018

Asenapine Sublingual Tablets

The FDA has approved Sigmapharm Laboratories’ asenapine sublingual tablets, 5 mg and 10 mg, the generic formulation of Saphris sublingual tablets, 5 mg and 10 mg (Forest Laboratories). Asenapine is used in the treatment of adults with bipolar I disorder as an adjunctive treatment to lithium or valproate.

Source: FDA, July 17, 2018

NEW INDICATIONS

Opdivo for Previously Treated Small-Cell Lung Cancer

Nivolumab (Opdivo, Bristol-Myers Squibb) has received FDA approval as the first immuno-oncology treatment for patients with metastatic small-cell lung cancer (SCLC) that has progressed after platinum-based chemotherapy and at least one other line of therapy.

Nivolumab was discontinued in 10% of patients, and one dose was withheld in 25% of patients for an adverse reaction. The most common adverse reactions were fatigue, decreased appetite, musculoskeletal pain, dyspnea, nausea, diarrhea, constipation, and cough. Serious adverse reactions occurred in 45% of patients.

The FDA granted this approval priority review.

Source: Bristol-Myers Squibb, August 17, 2018

Imbruvica Plus Rituximab for Waldenström’s Macroglobulinemia

The FDA has approved ibrutinib (Imbruvica, Janssen) in combination with rituximab (Rituxan, Genentech) for the treatment of Waldenström’s macro-globulinemia (WM), a rare blood cancer. Ibrutinib received FDA approval as a WM monotherapy in January 2015.

This approval is based on results from the randomized, double-blind, placebo-controlled iNNOVATE study, which evaluated ibrutinib in combination with rituximab versus placebo plus rituximab in 150 patients with either relapsed/refractory or previously untreated WM.

Warnings and precautions include the risk of hemorrhage, infections, cytopenias, cardiac arrhythmias, hypertension, second primary malignancies, tumor lysis syndrome, and embryo-fetal toxicity. The most common adverse reactions of all grades in patients treated with ibrutinib plus rituximab in iNNOVATE were bruising, musculoskeletal pain, hemorrhage, diarrhea, rash, arthralgia, nausea, and hypertension. Grade 3 or 4 infusion-related reactions were seen in 1% of patients treated with ibrutinib plus rituximab.

Source: Janssen, August 27, 2018

Lenvima for First-Line Treatment of Liver Cancer

The kinase inhibitor lenvatinib (Lenvima, Eisai Inc. and Merck) has received FDA approval for the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC).

This approval was based on results from REFLECT (Study 304), comparing lenvatinib with sorafenib (Nexavar, Bayer) in patients with previously untreated unresectable HCC. Patients treated with lenvatinib experienced a median overall survival of 13.6 months compared to 12.3 months with sorafenib.

Adverse reactions, some serious or fatal, may occur with lenvatinib, including hypertension, cardiac dysfunction, arterial thromboembolic events, hepatotoxicity, renal failure or impairment, proteinuria, diarrhea, fistula formation and gastrointestinal perforation, QT interval prolongation, hypocalcemia, reversible posterior leukoencephalopathy syndrome, hemorrhagic events, impairment of thyroid-stimulating hormone suppression/thyroid dysfunction, and wound-healing complications.

In REFLECT, the most common adverse reactions observed were hypertension, fatigue, diarrhea, decreased appetite, arthralgia/myalgia, decreased weight, abdominal pain, palmar-plantar erythrodysesthesia syndrome, proteinuria, dysphonia, hemorrhagic events, hypothyroidism, and nausea.

Source: Eisai Inc., August 17, 2018

Kalydeco for CF at Age 1

The FDA has expanded the use of ivacaftor (Kalydeco, Vertex Pharmaceuticals Inc.) to children as young as 12 months of age who have cystic fibrosis (CF) with at least one mutation in their cystic fibrosis transmembrane conductance regulator (CFTR) gene that is responsive to ivacaftor based on clinical and/or in vitro assay data.

This approval is based on data from the ongoing, phase 3, open-label safety study (ARRIVAL) of 25 children 12 months to less than 24 months of age who have CF with one of 10 CFTR mutations (G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, G1349D, or R117H). Mean baseline sweat chloride was 104.1 mmol/L (n = 14) at baseline and 33.8 mmol/L (n = 14) following 24 weeks of treatment with ivacaftor.

Most adverse events were mild or moderate, and no patient discontinued due to adverse events. The most common adverse events were cough (74%), pyrexia (37%), elevated aspartate aminotransferase (37%), elevated alanine aminotransferase (32%), and runny nose (32%). Four serious adverse events were seen in two patients.

Ivacaftor was already approved in the U.S. to treat CF in patients 2 years of age and older who have one of 38 ivacaftor-responsive mutations in the CFTR gene based on clinical and/or in vitro assay data.

Source: Vertex Pharmaceuticals, August 15, 2018

Orkambi for CF at Age 2

The FDA has expanded the use of lumacaftor/ivacaftor (Orkambi, Vertex Pharmaceuticals Inc.) to include children 2 years through 5 years of age with cystic fibrosis (CF) who have two copies of the F508del-CFTR mutation, making it the first medicine approved to treat the underlying cause of CF in this population.

This approval is based on a phase 3, open-label safety study in 60 patients that showed treatment with lumacaftor/ivacaftor was generally safe and well tolerated for 24 weeks, with a safety profile similar to that in patients 6 years of age and older. Improvements in sweat chloride, a secondary endpoint, were observed at week 24 (mean decrease from baseline, 31.7 mmol/L). Researchers also saw changes in key growth parameters.

The most common adverse event was cough (63%); most adverse events were mild or moderate. Four patients experienced serious adverse events and three discontinued treatment due to treatment-emergent adverse events or elevated liver function tests.

Lumacaftor/ivacaftor was already approved in the U.S. for the treatment of CF in patients 6 years of age and older who have two copies of the F508del-CFTR mutation.

Source: Vertex Pharmaceuticals, August 7, 2018

Granix for Younger Infants

The FDA has approved tbo-filgrastim injection (Granix, Teva Pharmaceutical Industries Ltd.) for a new vial presentation and indication in pediatric patients ages 1 month and older.

Tbo-filgrastim is indicated to reduce the duration of severe neutropenia in adult and pediatric patients ages 1 month and older with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.

The new vial presentation will be available in 300 mcg/1 mL and 480 mcg/1.6 mL single-dose vials. The prefilled syringe presentations will continue to be available as well.

Tbo-filgrastim was approved by the FDA in August 2012.

Source: Teva, August 6, 2018

NEW FORMULATIONS

Perseris, Extended-Release Risperidone for Schizophrenia

The FDA has approved Perseris (Indivior PLC), the first once-monthly, subcutaneous, long-acting injectable containing risperidone for the treatment of schizophrenia in adults. Clinically relevant levels were reached after the first injection without a loading dose or any supplemental oral risperidone.

Risperidone is a well-established treatment for schizophrenia, but adherence is a challenge. The extended-release delivery system forms a subcutaneous depot that provides sustained levels of risperidone over one month. Initial peak risperidone plasma levels occur within four to six hours of dosing due to an initial release of the drug during the depot formation process.

In a phase 3, randomized, double-blind, placebo-controlled, eight-week study of 354 patients, Perseris’ efficacy was demonstrated by an improvement in the primary clinical endpoint, Positive and Negative Syndrome Scale total score at day 57. The improvement in Clinical Global Impression Severity of Illness was also statistically significant at day 57.

The systemic safety profile of Perseris was consistent with the known safety profile of oral risperidone. The most common systemic adverse reactions in the phase 3 trial were increased weight, sedation/somnolence, and musculoskeletal pain. The most common injection-site reactions were injection-site pain and reddening of the skin.

Source: Indivior, July 27, 2018

Cequa for Dry Eye Disease

The FDA has approved cyclosporine ophthalmic solution, 0.09% (Cequa, Sun Pharmaceutical Industries Ltd.) to increase tear production in patients with keratoconjunctivitis sicca (dry eye).

Cequa provides the highest FDA-approved concentration of cyclosporine A (CsA). It is also the first approved CsA product that incorporates a nanomicellar technology, which allows the CsA molecule to overcome solubility challenges, penetrate the eye’s aqueous layer, and prevents the release of the active lipophilic molecule prior to penetration.

In a phase 3 trial, after 12 weeks of treatment, Cequa showed statistically significant improvement in the primary endpoint, Schirmer’s score (a measurement of tear production) compared to vehicle. Cequa is dosed twice daily and will be available as a single-use vial.

Source: Sun, August 16, 2018

Tiglutik for ALS

The FDA has approved riluzole oral suspension (Tiglutik, ITF Pharma) for the treatment of amyotrophic lateral sclerosis (ALS). The first easy-to-swallow, thickened riluzole liquid was designed to overcome the challenges of disease-related dysphagia in ALS. It is administered twice daily via an oral syringe.

Riluzole is used to slow the progression of ALS. Tiglutik precludes the need for manipulation of tablets by patients or caregivers, easing administration, and may provide for more accurate dosing and enhanced patient compliance.

The approval was based on bioavailability studies comparing oral riluzole tablets to Tiglutik oral suspension. The most common side effects of Tiglutik are consistent with the established clinical profile of riluzole and include oral hypoesthesia, asthenia, nausea, decreased lung function, hypertension, and abdominal pain.

Tiglutik received FDA fast-track and orphan drug designations.

Source: ITF Pharma, September 6, 2018

Jornay PM Extended-Release Methylphenidate for ADHD

The FDA has approved Jornay PM (Ironshore Pharmaceuticals & Development), a novel formulation of methylphenidate that is taken in the evening to treat attention-deficit/hyperactivity disorder (ADHD) in patients 6 years of age and older. Jornay PM has demonstrated improvement in the severity of ADHD symptoms in the early morning and throughout the day.

Jornay PM is the first drug utilizing Ironshore’s proprietary drug-delivery platform, Delexis, which contains two functional film coatings that act synergistically to achieve a unique pharmacokinetic profile. The first layer delays the initial release of drug for up to 10 hours while the second helps to control the rate of release of the active pharmaceutical ingredient throughout the day.

The effectiveness of Jornay PM was established in two phase 3, multicenter, randomized, double-blind, placebo-controlled studies conducted in 278 pediatric patients 6 to 12 years of age with a diagnosis of ADHD.

Source: Ironshore, August 9, 2018

Altreno for Acne

Tretinoin 0.05% lotion (Altreno, Ortho Dermatologics) has secured FDA approval for the topical treatment of acne vulgaris in patients 9 years of age and older. Altreno is the first formulation of tretinoin in a lotion.

Extensive clinical data has shown that retinoids are highly effective in treating acne, but a common perceived barrier to their use is that retinoid treatment is associated with skin irritation. In clinical trials, Altreno lotion provided the efficacy of tretinoin, a retinoid, in a generally well-tolerated formulation, with skin dryness, pain, swelling, irritation, and peeling reported in 4% or less of patients.

The most common adverse reactions were dryness, pain, erythema, irritation, and exfoliation.

Source: Ortho Dermatologics, August 24, 2018

FDA REVIEW ACTIVITIES

Breakthrough Therapy Status

Quizartinib for Acute Myeloid Leukemia

Daiichi Sankyo has been granted a breakthrough therapy designation for quizartinib, an investigational FLT3 inhibitor, for the treatment of adults with relapsed/refractory FLT3-ITD acute myeloid leukemia (AML).

The FLT3-ITD gene mutation affects approximately one in four AML patients. Relapsed/refractory FLT3-ITD AML is very aggressive, with increased incidence of relapse, risk of death following relapse, and relapse following hematopoietic stem cell transplantation compared to those without this mutation. Treatment options are limited.

The breakthrough therapy designation was granted based on results of the phase 3 QuANTUM-R study. Quizartinib is the first FLT3 inhibitor to significantly improve overall survival as an oral, single agent compared with chemotherapy. The safety profile observed in QuANTUM-R appears consistent with that observed at similar doses in the quizartinib clinical development program. Incidence of treatment-emergent adverse events was comparable between patients who received single-agent quizartinib and those who received salvage chemotherapy.

Source: Daiichi Sankyo, August 1, 2018

Braftovi With Mektovi for Metastatic Colorectal Cancer

The FDA has granted a breakthrough therapy designation to Array BioPharma Inc. for encorafenib (Braftovi) in combination with binimetinib (Mektovi) and cetuximab for the treatment of patients with BRAF V600E-mutant metastatic colorectal cancer (mCRC) after failure of one or two prior lines of therapy for metastatic disease.

Results from the safety lead-in of the ongoing, randomized, phase 3 BEACON CRC trial showed that, at the time of analysis, overall survival (OS) data were fully mature through 12.6 months and the median OS had not yet been reached. The one-year OS rate for this cohort was 62%. Median progression-free survival for patients treated with the triplet was eight months and was similar between patients receiving one or two prior lines of therapy. The confirmed overall response rate was 48%, and among the 17 patients who had received only one prior line of therapy, it was 62%.

Source: Array BioPharma Inc., August 7, 2018

Xolair for Food Allergies

Genentech has been given a breakthrough therapy designation for omalizumab (Xolair) to prevent severe allergic reactions to a range of food allergens, including peanut, milk, and egg. As many as 15 million Americans have food allergies, which result in an estimated 200,000 emergency-room visits each year. There are no FDA-approved treatments that help prevent severe reactions due to food allergies.

Xolair is an injectable prescription medicine approved to treat moderate-to-severe persistent asthma in patients 6 years of age or older whose asthma symptoms are not controlled by inhaled corticosteroids. It is also approved to treat chronic idiopathic urticaria in patients ages 12 and older whose hives are not controlled by H1 antihistamines.

Source: Genentech, August 13, 2018

Lenvima With Keytruda for Endometrial Carcinoma

Eisai and Merck have been granted a breakthrough therapy designation for lenvatinib (Lenvima, Eisai), an orally available kinase inhibitor, in combination with pembrolizumab (Keytruda, Merck), an anti–programmed-death-1 therapy. The dual therapy is a potential treatment for patients with advanced and/or metastatic nonmicrosatellite instability high (MSI-H)/proficient mismatch repair (pMMR) endometrial carcinoma (EC) who have progressed following at least one prior systemic therapy.

The designation was based on interim results of the EC cohort in Study 111/KEYNOTE-146, a multicenter, open-label, single-arm phase 1b/2 basket trial in patients with selected solid tumors. A randomized, international, two-arm phase 3 study in recurrent EC is also under way (Study 309/KEYNOTE-775).

Source: Eisai and Merck, July 31, 2018

Priority Review Status

Empliciti, Pomalyst for Multiple Myeloma

The FDA has granted Bristol-Myers Squibb priority review for its supplemental biologics license application for elotuzumab (Empliciti) in combination with pomalidomide (Pomalyst, Celgene) and low-dose dexamethasone (Pd). The combination treatment (EPd) is intended for patients with relapsed/refractory multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor.

Empliciti is an immunostimulatory antibody that specifically targets signaling lymphocyte activation molecule family member 7 (SLAMF7), a cell-surface glycoprotein expressed on myeloma cells independent of cytogenetic abnormalities. SLAMF7 also is expressed on natural killer cells, plasma cells, and at lower levels on specific immune cell subsets.

Empliciti directly activates the immune system through natural killer cells via the SLAMF7 pathway, and it also targets SLAMF7 on myeloma cells for natural killer cell–mediated destruction via antibody-dependent cellular toxicity.

The application is based on data from ELOQUENT-3, a phase 2 study in which patients randomized to EPd experienced a 46% reduction in risk of disease progression compared with patients randomized to Pd alone, with median progression-free survival of 10.3 months compared with 4.7 months in Pd patients.

Source: Bristol-Myers Squibb, August 23, 2018

ALXN1210 for Paroxysmal Nocturnal Hemoglobinuria

The FDA has accepted for priority review Alexion Pharmaceuticals’ biologics license application for ALXN1210, a long-acting C5 complement inhibitor. ALXN1210 is intended for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH). The FDA set a Prescription Drug User Fee Act date of February 18, 2019.

PNH is a chronic, progressive, debilitating, and potentially life-threatening ultra-rare blood disorder that can strike anyone without warning. In PNH, chronic, uncontrolled activation of the complement system destroys red blood cells. It has been estimated that one in three patients with PNH do not survive more than five years after diagnosis.

ALXN1210 inhibits the C5 protein in the terminal complement cascade. In phase 3 clinical studies in complement inhibitor–naïve patients with PNH, and patients with PNH who had been stable on eculizumab (Soliris, Alexion), intravenous treatment with ALXN1210 every eight weeks demonstrated noninferiority to intravenous treatment with eculizumab every two weeks.

Source: Alexion, August 20, 2018

Fast-Track Designations

Inhaled Xenon Gas for Cardiac Arrest

Mallinckrodt PLC and NPXe Ltd. have been granted a fast-track designation for NPXe’s phase 3 trial of xenon gas for inhalation in post-cardiac arrest patients.

Xenon is a noble gas that has been used as an inhaled therapy in several studies. In post-cardiac arrest syndrome, more N-methyl-D-aspartate receptors (NMDARs) are activated, causing extreme ion imbalances, neuronal damage, and cell death. Studies have shown that xenon may help inhibit NMDARs through action at the glycine-binding site. Xenon also may help moderate the flow of damaging ions through the calcium channel. Thus, by mitigating neuronal damage and cell death, xenon may improve functional outcomes and reduce mortality rates in cardiac arrest survivors.

Source: Mallinckrodt PLC and NPXe Ltd., August 23, 2018

Diacerein 1% Ointment for Epidermolysis Bullosa Simplex

The FDA has granted a fast-track designation to Castle Creek Pharmaceuticals for diacerein 1% ointment (CCP-020) for the treatment of epidermolysis bullosa simplex (EBS). EBS is a subtype of epidermolysis bullosa, a genetic condition that causes extremely fragile skin that blisters and peels in response to minor injury. There are no approved treatment options for any form of EBS.

Diacerein is a slow-acting small molecule of the anthraquinone class with potent anti-inflammatory properties. Diacerein and its active metabolite rhein have been shown to inhibit the production and activity of interleukin 1-beta and other pro-inflammatory cytokines. In CCP-020, diacerein is hydrolyzed to rhein in the epidermis and dermis following topical administration and is believed to block an inflammatory signaling pathway associated with EBS, strengthening epidermal tissue and healing skin blisters.

In a phase 2 trial involving 17 EBS patients, 60% of those treated with a diacerein cream formulation experienced at least a 40% reduction in blistering after four weeks, compared with 18% on vehicle. Six patients on diacerein and 11 on vehicle experienced adverse events, notably increases in blistering, pruritus, and skin infection. However, none of the events were considered treatment-related.

Source: Castle Creek Pharmaceuticals, August 9, 2018

AVB-S6-500 for Recurrent Ovarian Cancer

Aravive Biologics, Inc., has been granted a fast-track designation for AVB-S6-500 as a potential treatment for platinum-resistant recurrent ovarian cancer.

AVB-S6-500 is a novel, high-affinity, soluble Fc-fusion protein designed to block the activation of the GAS6-AXL signaling pathway by intercepting the binding of GAS6 to its receptor AXL. Research has shown GAS6–AXL signaling to be a key pathway that promotes tumor growth and metastases, as well as immune evasion and resistance to other anticancer agents. AXL and GAS6 expression correlate with poor prognosis in cancer.

Results of a phase 1 study of AVB-S6-500 in healthy volunteers showed a favorable safety profile. Aravive is initiating the phase 1b portion of a planned phase 1b/2 study combining AVB-S6-500 with standard-of care therapies in patients with platinum-resistant ovarian cancer before the end of the year.

Source: Aravive Biologics, August 20, 2018

Vicinium for Nonmuscle Invasive Bladder Cancer

The FDA has granted fast-track status to Vicinium (Sesen Bio) for the treatment of BCG-unresponsive high-grade nonmuscle invasive bladder cancer (NMIBC). Vicinium is composed of a recombinant fusion protein that targets epithelial-cell adhesion molecule (EpCAM) antigens on the surface of tumor cells to deliver a potent protein payload, Pseudomonas Exotoxin A (ETA).

Vicinium is constructed with a stable, genetically engineered peptide linker to ensure the payload remains attached until it is internalized by the cancer cell, which is believed to reduce toxicity to healthy tissues. In prior clinical trials, EpCAM has been shown to be overexpressed in NMIBC cells, with minimal to no EpCAM expression observed on normal bladder cells. Sesen Bio believes that Vicinium’s cancer-cell-killing properties promote an antitumor immune response that may combine well with immuno-oncology drugs.

Vicinium is being evaluated in the phase 3 VISTA registration trial for the treatment of patients with high-grade NMIBC who have previously received two courses of Bacillus Calmette-Guérin (BCG) and whose disease is now BCG-unresponsive.

Source: Sesen Bio, August 9, 2018

Orphan Drug Designations

PLN-74809 for Idiopathic Pulmonary Fibrosis

The FDA has granted an orphan drug designation for PLN-74809 (Pliant Therapeutics) for the treatment of idiopathic pulmonary fibrosis (IPF).

IPF is a chronic and progressive fibrotic disease in which lung tissue becomes thickened, stiff, and scarred. As the fibrosis progresses, it becomes increasingly difficult for the lungs to transfer oxygen into the bloodstream—ultimately causing vital organs to break down. IPF affects approximately 140,000 people in the U.S.

In preclinical studies, PLN-74809 modulated fibrotic tissue-specific integrins, which selectively block activation of transforming growth factor beta, preventing the growth of fibrotic tissue in the lungs and liver.

Source: Pliant Therapeutics, August 6, 2018

Livantra for Pulmonary Arterial Hypertension

Martin Pharmaceuticals has been granted orphan drug status for trimetazidine (Livantra) in the treatment of pulmonary arterial hypertension (PAH). Earlier this year, Livantra received an orphan drug designation for the treatment of acute-on-chronic liver failure.

In PAH, arteries throughout the lungs narrow, increasing the resistance to blood flow. In an effort to compensate, blood pressure intensifies in the pulmonary artery, ultimately damaging the right ventricle. An estimated 35,000 to 60,000 people in the U.S. have PAH. Despite improvements in patient management, PAH mortality rates remain high.

Livantra is a repurposed, reformulated liquid version of trimetazidine, an anti-ischemic compound principally used in the treatment of angina pectoris.

Source: Martin Pharmaceuticals, August 14, 2018

OSP-101 for Bronchiolitis Obliterans

OSP-101 (Onspira) has been designated an orphan drug for the treatment for bronchiolitis obliterans (BO), a progressive inflammatory condition that is the leading cause of morbidity and mortality in the lung-transplant population.

More than half of patients develop BO within five years post-transplant, and this increases to nearly 80% by 10 years. BO may also occur following hematopoietic stem-cell transplantation and after exposure to certain chemicals. There are no approved drugs for the treatment of BO.

OSP-101, an inhaled interleukin-1 receptor antagonist, is delivered directly to the lungs. OSP-101 is also under evaluation for idiopathic pulmonary fibrosis, cystic fibrosis, and other causes of BO.

Source: Onspira Therapeutics, August 14, 2018

AL001 for Frontotemporal Dementia

The FDA has granted orphan drug designation to AL001 (Alector), a human recombinant monoclonal antibody, for the treatment of all patients with frontotemporal dementia (FTD).

FTD is the second most common early-onset form of dementia after Alzheimer’s disease, afflicting approximately 60,000 Americans. It is a rapidly progressing degenerative syndrome characterized by prominent cognitive dysfunction, behavioral and personality changes, and language deficits. Most patients die within 10 years of its onset.

AL001 is designed to increase the levels in the brain of progranulin, a secreted immune modulatory factor which, when mutated, leads to FTD.

Source: Alector, August 8, 2018

ALT-P7 for Gastric Cancer

Alteogen Inc. has received an orphan drug designation for ALT-P7, a treatment for gastric cancer. ALT-P7 is a conjugate using a trastuzumab variant form of antibody. It is undergoing a first-in-human phase 1 clinical trial for breast cancer patients. Alteogen is planning a phase 2 clinical trial for breast cancer patients in 2019. Following the current breast-cancer trial, Alteogen will extend the clinical development of ALT-P7 to gastric cancer; it has already proven efficacy in preclinical in vitro and in vivo studies.

Source: Alteogen Inc., August 6, 2018

Lurbinectedin for Small-Cell Lung Cancer

PharmaMar has received orphan drug status for lurbinectedin for the treatment of small-cell lung cancer (SCLC). About 18% of all lung cancer cases are SCLC, and more than 34,000 new U.S. diagnoses are recorded every year.

SCLC is a very aggressive cancer that usually presents with distant metastases and has already spread at the time of diagnosis, limiting the role of traditional approaches and worsening the prognosis compared to other lung cancers. The five-year survival rate is about 5%.

Lurbinectedin (PM1183) inhibits RNA polymerase II, an enzyme essential for the transcription process that is overactivated in tumors with transcription addiction.

Source: PharmaMar, August 3, 2018

AGT-184 for Mucopolysaccharidosis

The FDA has designated AGT-184 (ArmaGen, Inc.) an orphan drug for the treatment of mucopolysaccharidosis type IIIA (also known as Sanfilippo Syndrome A or MPS IIIA).

MPS IIIA is a lysosomal storage disease caused by a deficiency in the gene encoding for the enzyme N-sulfoglucosamine sulfohydrolase (SGSH), which results in a buildup of complex sugar polymers in the brain, leading to progressive intellectual disability and developmental regression.

AGT-184 is an immunoglobulin G-SGSH fusion protein. In a mouse model, a surrogate version of AGT-184 reduced heparan sulfate levels by 70% in the brain and 85% in the liver.

Source: ArmaGen, August 2, 2018

Complete Response Letter

Dasotraline for ADHD

The FDA has issued a complete response letter for the new drug application for dasotraline (Sunovion Pharmaceuticals Inc.), a novel dual-acting dopamine and norepinephrine reuptake inhibitor for the treatment of attention-deficit/hyperactivity disorder (ADHD).

The agency indicated that additional clinical data are needed to evaluate the efficacy and tolerability of dasotraline. Sunovion plans to meet with the FDA to discuss its comments and determine next steps, but said it remains confident about dasotraline’s future.

Dasotraline has been evaluated in approximately 2,500 children and adults with ADHD in multiple placebo-controlled safety and efficacy studies, as well as two long-term safety studies.

Source: Sunovion, August 31, 2018

Label Update

Keytruda for NSCLC

The FDA has approved an expanded label for pembrolizumab (Keytruda, Merck) based on results of the KEY-NOTE-189 trial.

The trial included patients with metastatic nonsquamous non–small-cell lung cancer with no EGFR or ALK genomic tumor aberrations. Regardless of programmed death ligand-1 tumor expression, pembrolizumab in combination with pemetrexed (Alimta, Eli Lilly) and platinum chemotherapy as first-line treatment demonstrated a statistically significant and clinically meaningful improvement in overall survival, reducing the risk of death by half compared to chemotherapy alone (hazard ratio [HR], 0.49). The study also showed a significant improvement in progression-free survival compared to chemotherapy alone (HR, 0.52).

Source: Merck, August 20, 2018

Eylea Dosing Data

The FDA has approved an updated label for aflibercept injection (Eylea, Regeneron Pharmaceuticals, Inc.) in patients with wet age-related macular degeneration (AMD). The label includes second-year data from the phase 3 VIEW 1 and 2 trials, in which patients were treated with a modified 12-week dosing schedule (doses given at least every 12 weeks). Aflibercept is also approved in wet AMD for every four- or eight-week dosing intervals after three initial monthly doses.

Aflibercept is a vascular endothelial growth factor (VEGF) inhibitor formulated as an injection for the eye. It is designed to block the growth of new blood vessels and decrease vascular permeability in the eye by blocking VEGF-A and placental growth factor (PLGF), two growth factors involved in angiogenesis.

Source: Regeneron, August 17, 2018

DRUG SAFETY ISSUES

“Just Enhance” Sales Halted

A federal court has ordered S. Hackett Marketing LLC (doing business as Just Enhance) to stop selling unapproved and misbranded drugs to consumers using more than 100 websites, the FDA says.

The U.S. District Court for the District of New Jersey issued a permanent injunction requiring S. Hackett Marketing; R. Thomas Marketing LLC; Shawn Hackett, president and owner of Just Enhance; and Roger Thomas, president and founder of R. Thomas Marketing LLC, to cease the distribution of drugs until they take specific remedial measures.

According to the complaint, the label on the defendants’ products claimed that the products could treat or prevent a variety of serious conditions, including erectile dysfunction, impotence, and prostatitis. The complaint stated the products were misbranded because they did not include adequate directions for use and their labels omitted material information.

The FDA issued a warning letter to the companies after conducting a laboratory analysis that revealed the presence of an undeclared pharmaceutical ingredient (sildenafil) in several products.

Source: FDA, August 30, 2018

Montelukast Tablets

Lot MON17384 of montelukast sodium tablets from Camber Pharmaceuticals, Inc., in Piscataway, NJ, has been recalled because some sealed bottles labeled as containing 30 10-mg montelukast sodium tablets were found instead to contain 90 50-mg losartan potassium tablets.

Montelukast sodium tablets are beige, rounded square-shaped, film-coated tablets imprinted with “I” on one side and “114” on the reverse. Losartan tablets are white and oval-shaped with the letter “I” imprinted on one side and the number “5” imprinted on the reverse. The recalled lot expires on December 31, 2019.

Source: FDA, August 31, 2018

Azithromycin and Cancer

The antibiotic azithromycin (Zithromax, Zmax) should not be given long-term to prevent bronchiolitis obliterans in patients with cancers of the blood or lymph nodes who undergo a donor stem-cell transplant, the FDA warns. A clinical trial found an increased rate of relapse in cancers affecting the blood and lymph nodes, including death, in these patients.

Bronchiolitis obliterans syndrome (BOS) is caused by inflammation and scarring in the lungs, resulting in severe shortness of breath and dry cough. Cancer patients who undergo stem-cell transplants from donors are at risk for BOS. Azithromycin is not approved for preventing BOS, and there are no known effective antibiotic treatments for BOS prophylaxis.

Researchers in France identified this issue while conducting a clinical trial investigating the effectiveness of long-term azithromycin to prevent BOS in patients who undergo allogeneic stem-cell transplants for cancers of the blood and lymph nodes. The researchers stopped the ALLOZITHRO1 trial about 13 months after completing enrollment of 480 patients because of an unexpected increase in the rate of cancer relapses and death in patients taking azithromycin.

Source: FDA, August 3, 2018

DEVICE APPROVALS

TMS for OCD

The FDA has permitted marketing of the Brainsway Deep Transcranial Magnetic Stimulation System (Brainsway Ltd.) for the treatment of obsessive compulsive disorder (OCD).

The FDA permitted marketing of trans-cranial magnetic stimulation (TMS) as a treatment for major depression in 2008 and expanded its use to treat pain associated with certain migraine headaches in 2013.

The FDA reviewed a randomized, multicenter study of 100 patients; 49 received treatment with the Brainsway device and 51 received treatment with a sham device. Patients already receiving medical management of OCD were maintained at current dosages throughout the study. Thirty-eight percent of patients responded to the Brainsway device, whereas 11% of patients responded using the sham device.

The most frequent adverse reaction was headache, reported by 37.5% of patients using the Brainsway device and 35.3% of patients using the sham treatment. No serious adverse reactions related to the Brainsway device were reported.

Source: FDA, August 17, 2018

Actifuse Flow for Bone Grafts

The FDA has cleared Actifuse Flow Bone Graft Substitute (Baxter International Inc.) for use in a variety of orthopedic surgical procedures.

Actifuse Flow offers accelerated bone growth in a prepackaged delivery syringe for precise placement into small bony voids or gaps in the skeletal system. It uses the proprietary silicate-substituted technology of Baxter’s Actifuse Bone Graft Substitute, which enhances silicon levels to accelerate bone formation.

Actifuse Flow comes ready to use with no mixing or preparation, maintains its flowable consistency throughout surgery, and is delivered directly from a pre-loaded syringe with the ability to start and stop delivery. As the graft substitute resorbs, it is replaced by the patient’s own bone during the healing process.

Source: Baxter International, September 6, 2018

Sonata for Fibroid Treatment

The Sonata Sonography-Guided Trans-cervical Fibroid Ablation System (Gynesonics) has received 510(k) clearance from the FDA. It is the first intrauterine ultrasound system with a proprietary radiofrequency ablation device, providing a transcervical, incision-free, uterus-preserving treatment for uterine fibroids.

In the pivotal clinical trial used to support the FDA regulatory filing, the co-primary endpoints included a significant reduction in bleeding and a high rate of freedom from surgical reintervention due to heavy menstrual bleeding. The safety outcomes were also favorable, including zero device-related adverse events reported in the 147-patient trial.

Source: Gynesonics, August 22, 2018

Hysteroscopy in the Office

The Luminelle DTx Hysteroscopy System (UVision 360) has received 510(k) clearance from the FDA, with a dual indication for hysteroscopy and cystoscopy. The small device has the potential for an affordable, accurate patient diagnosis and/or therapeutic procedure in one doctor’s office visit.

The Luminelle DTx Hysteroscopy System allows physicians to see the uterus’ internal lining from an optimal distance with clarity. It may help prevent “blind” biopsies and allow physicians to offer either a therapeutic diagnosis or a biopsy under visualization without the need for a hospital operating room.

Source: UVision 360, August 21, 2018

Hydrus Microstent

The FDA has approved the Hydrus Microstent (Ivantis), a micro-invasive glaucoma surgery (MIGS) device used to treat mild-to-moderate primary open-angle glaucoma in conjunction with cataract surgery.

Roughly the size of an eyelash, the Hydrus Microstent is designed to reduce eye pressure by re-establishing flow through Schlemm’s canal, the eye’s natural outflow pathway. It is placed into the trabecular meshwork and the canal during micro-invasive glaucoma surgery.

Source: Ivantis, August 13, 2018

DEVICE SAFETY ISSUES

Rupture of Membranes Tests

The improper use of tests meant to help doctors determine whether a pregnant woman’s water has broken may be associated with a series of health complications reported to the FDA that includes 13 fetal deaths, the agency says.

A rupture of the membranes (ROM) containing amniotic fluid can pose immediate and severe risks to the woman and the developing fetus without proper patient management and timely intervention. The FDA is concerned that misuse, relying solely on ROM tests without using other assessments, and inaccurate interpretation of lab results of ROM tests could result in an increased risk of fetal harm or death.

The FDA issued a letter to health care providers reminding them that the labeling for these tests specifies that they should not be used on their own to independently diagnose a ROM in pregnant women. These tests have only been cleared for marketing by the FDA to be used by health care providers in conjunction with other clinical assessments to make critical patient management decisions regarding whether a ROM has occurred.

The ROM is a normal occurrence once a woman is in labor. However, if ROM occurs prior to the onset of labor, it can cause an increased risk of infection and injury to the fetus and mother. Health care providers use ROM tests to aid in diagnosing ruptured membranes in pregnant women through analysis of vaginal secretions. ROM tests are point-of-care tests that provide on-site information to providers.

ROM tests may provide a false negative result; without additional clinical assessment, providers may incorrectly assume ROM has not occurred.

Source: FDA, August 8, 2018