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P T. 2017;42(2): 78-85, 96

Drug and Device News February 2017


Rubraca for Ovarian Cancer

The FDA has granted accelerated approval to rucaparib (Rubraca, Clovis Oncology) to treat women with advanced ovarian cancer who have been treated with two or more chemotherapies and whose tumors have a specific gene mutation (deleterious BRCA), as identified by an FDA-approved companion diagnostic test.

The agency also approved the FoundationFocus CDxBRCA (Foundation Medicine, Inc.) companion diagnostic for use with rucaparib. The test detects the presence of deleterious BRCA gene mutations in the tumor tissue of ovarian cancer patients. If one or more of the mutations are detected, the patient may be eligible for treatment with rucaparib.

Source: FDA, December 19, 2016

Spinraza for Spinal Muscular Atrophy

Nusinersen (Spinraza, Biogen/Ionis Pharmaceuticals) has received FDA approval as the first drug to treat children and adults with spinal muscular atrophy (SMA), a rare and often fatal genetic disease affecting muscle strength and movement. Nusinersen is an injection administered into the fluid surrounding the spinal cord.

The efficacy of nusinersen was investigated in a study of 121 patients with infantile-onset SMA who were diagnosed before 6 months of age and who were less than 7 months old at the time of their first dose. The FDA asked the sponsor to conduct an interim analysis as a way to evaluate the study results as early as possible; 82 patients were eligible for this analysis. Forty percent of the patients treated with nusinersen achieved improvements in motor milestones as defined in the study, whereas none of the control patients did.

Source: Biogen, December 27, 2016

Synjardy ER for Diabetes

The FDA has given the green light to Synjardy XR (empagliflozin and metformin hydrochloride extended-release tablets, Boehringer Ingelheim/Eli Lilly) for the treatment of adults with type-2 diabetes (T2D). When used along with diet and exercise, Synjardy XR is indicated to improve blood sugar in adults with T2D when both empagliflozin and metformin can be taken. Standard Synjardy tablets were approved in 2015.

Empagliflozin, a sodium-glucose cotransporter 2 inhibitor, removes excess glucose through the urine by blocking glucose reabsorption in the kidney. Metformin, a commonly prescribed initial treatment for T2D, lowers glucose production by the liver and its absorption in the intestine.

Source: Eli Lilly, December 12, 2016

Adynovate Antihemophilic Factor

The FDA has approved Adynovate (antihemophilic factor [recombinant], PEGylated, Shire), an extended circulating half-life recombinant factor VIII treatment for pediatric patients under 12 years of age with hemophilia A. The FDA also approved Adynovate for use in surgical settings in both adult and pediatric patients. Adynovate is built on the full-length Advate (antihemophilic factor [recombinant]) molecule, a leading treatment for patients with hemophilia A, with more than 13 years of real-world patient experience.

Source: Shire, December 27, 2016

Eucrisa Ointment for Eczema

Crisaborole ointment (Eucrisa, Anacor Pharmaceuticals) has secured FDA approval to treat mild-to-moderate eczema (atopic dermatitis) in patients 2 years of age and older. Crisaborole, applied topically twice daily, is a phosphodiesterase 4 inhibitor, although its specific mechanism of action in atopic dermatitis is not known.

Source: FDA, December 14, 2016


Maci for the Repair of Knee Cartilage Defects

The FDA has approved Maci (autologous cultured chondrocytes on a porcine collagen membrane, Vericel Corporation) for the repair of symptomatic, full-thickness cartilage defects of the knee in adults. Maci is the first FDA-approved product that applies the process of tissue engineering to grow cells on scaffolds using healthy cartilage tissue from the patient’s own knee.

Each Maci implant consists of a small cellular sheet containing 500,000 to 1,000,000 cells per square centimeter (approximately 0.16 square inches). The amount of Maci administered depends on the size of the cartilage defect, and the membrane is trimmed to ensure that the damaged area is completely covered. Multiple implants may be used if there is more than one defect.

Source: FDA, December 13, 2016

Generic Approvals and Launches Epinephrine Injection

Mylan has launched an authorized generic for the EpiPen autoinjector (epinephrine injection, USP) at a wholesale acquisition cost (WAC) of $300 per epinephrine injection two-pack, which is more than 50% lower than the WAC of the company’s EpiPen 2-Pak autoinjectors. The authorized generic has the same drug formulation and device functionality as the EpiPen autoinjector and is administered the same way.

Source: Mylan, December 16, 2016

Oseltamivir Phosphate Capsules

Alvogen has launched the first generic equivalent to Tamiflu (oseltamivir phosphate capsules, Hoffman–La-Roche) in the United States. The product is available in 30-mg, 45-mg, and 75-mg strengths. Alvogen expects this generic equivalent to Tamiflu to deliver savings for patients and health providers of up to $500 million during the 2016–2017 flu season.

Source: Alvogen, December 12, 2016


Lucentis for Eye Disorder

The FDA has approved ranibizumab (Lucentis, Genentech) 0.5-mg injection for the treatment of patients with myopic choroidal neovascularization (mCNV), a complication of severe nearsightedness that can lead to blindness. In the United States, ranibizumab was previously approved for the treatment of patients with wet age-related macular degeneration; macular edema after retinal vein occlusion; diabetic macular edema (DME); and diabetic retinopathy in people with DME.

The new approval was based on results from the phase 3, randomized, double-blind, active-controlled RADIANCE trial, which compared the efficacy and safety of ranibizumab injection (0.5 mg) with that of verteporfin photodynamic therapy (vPDT) in 276 patients with visual impairment due to mCNV. At month 3, two ranibizumab groups had a mean change in best corrected visual acuity (BCVA) of +12.1 and +12.5 letters from baseline, respectively, compared with a mean BCVA change of +1.4 letters in the vPDT group.

Source: Genentech, January 5, 2017

Jardiance for Diabetic CV Risk

The FDA has approved a new indication for empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) to reduce the risk of cardiovascular (CV) death in adults with type-2 diabetes (T2D) and established CV disease. Empagliflozin is the first T2D treatment with this additional indication and the only oral T2D medication shown in a clinical trial to provide a life-saving CV benefit, according to the manufacturers.

In the EMPA-REG OUTCOME trial, empagliflozin significantly reduced the combined primary endpoint (the time to the first occurrence of CV death, nonfatal heart attack, or nonfatal stroke) by 14% compared with placebo (hazard ratio [HR], 0.86); the absolute risk reduction was 1.6% for empagliflozin compared with placebo. This primary finding was driven by a significant 38% reduction in the risk of CV death (HR, 0.62); the absolute risk reduction was 2.2% for patients treated with empagliflozin compared with those given placebo. There was no change in the risk of nonfatal heart attack (HR, 0.87) or nonfatal stroke (HR, 1.24).

Source: Boehringer Ingelheim, January 5, 2017


Priority Review Designations

Niraprib for Ovarian Cancer

The FDA has granted priority review of the new drug application for niraparib (Tesaro, Inc.). Niraparib is a poly(ADP-ribose) polymerase inhibitor that is being evaluated as a potential new treatment option for patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer after responding to platinum-based chemotherapy. The FDA has established a target action date of June 30, 2017.

The niraparib application was supported by data from a phase 3, double-blind, placebo-controlled, international trial that enrolled 553 patients with recurrent ovarian cancer who had achieved either a partial response or a complete response to their most-recent platinum-based chemotherapy. Among patients who were germline BRCA mutation carriers, median progression-free survival (PFS) for those treated with niraparib was 21.0 months compared with 5.5 months for control (P < 0.0001). Among patients in the nongermline BRCA mutant cohort, the median PFS for patients treated with niraparib was 9.3 months compared with 3.9 months for control (P < 0.0001).

Source: Tesaro, December 20, 2016

Stivarga for Liver Cancer

The FDA has granted priority review status to a supplemental new drug application for regorafenib (Stivarga, Bayer) for the second-line treatment of patients with unresectable hepatocellular carcinoma (uHCC).

The regulatory submission was based on data from the phase 3 RESORCE trial, which investigated regorafenib in patients with uHCC whose disease had progressed during treatment with sorafenib (Nexavar, Bayer/Onyx Pharmaceuticals). Regorafenib significantly improved overall survival (OS) compared with placebo (hazard ratio, 0.63; P < 0.001), which represented a 37% reduction in the risk of death for patients who received regorafenib plus best supportive care (BSC) compared with patients treated with placebo plus BSC. The median OS was 10.6 months in patients treated with regorafenib plus BSC compared with 7.8 months in patients who received placebo plus BSC.

Source: Bayer, January 4, 2017

Betrixaban for VTE

The FDA has accepted a new drug application granting priority review for betrixaban (Portola Pharmaceuticals), an oral, once-daily factor Xa-inhibitor anticoagulant, for extended-duration prophylaxis of venous thromboembolism (VTE) in acute medically ill patients with risk factors for VTE. The application for betrixaban, an FDA-designated fast-track investigational drug, has a Prescription Drug User Fee Act action date of June 24, 2017.

Source: Portola Pharmaceuticals, December 23, 2016

Durvalumab for Bladder Cancer

The FDA has accepted a biologics license application for durvalumab (AstraZeneca/MedImmune) and has granted the medication priority review status, with the Prescription Drug User Fee Act action date set for the second quarter of 2017.

Durvalumab is an investigational human monoclonal antibody directed against programmed death ligand-1 (PD-L1). PD-L1 is expressed by tumors to evade detection by the immune system through binding to programmed death-1 (PD-1) proteins on cytotoxic T lymphocytes. Durvalumab blocks the PD-L1 interaction with PD-1, thereby countering the tumor’s immune-evading tactics.

Source: AstraZeneca, December 9, 2016

Fast-Track Designations

APL-2 for PNH

The FDA has granted a fast-track designation to the development program for APL-2 (Apellis Pharmaceuticals), a complement C3 inhibitor, for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) who continue to experience hemolysis and require transfusions of red blood cells despite receiving therapy with eculizumab. PNH is a rare, acquired, potentially life-threatening disease characterized by complement-mediated hemolytic anemia. APL-2 is a synthetic cyclic peptide that binds specifically to C3 and C3b, effectively blocking all three pathways of complement activation.

Source: Apellis Pharmaceuticals, December 20, 2016

ASP0892 Vaccine for Peanut Allergy

The drug candidate ASP0892 (Astellas Pharma/Immunomic Therapeutics), a DNA vaccine for the mitigation of severe hypersensitivity reactions due to peanut allergy, has been granted FDA fast-track status. A phase 1 clinical trial has been initiated to evaluate the safety, tolerability, and immune response of ASP0892 in adults who are allergic to peanuts.

Source: Astellas Pharma, December 20, 2016

Breakthrough Therapy Status

Neridronic Acid for CRPS

The FDA has granted a breakthrough therapy designation to neridronic acid (Grünenthal/Abiogen Pharma), an investigational medication for the treatment of patients with complex regional pain syndrome (CRPS), a serious, disabling orphan disease. CRPS is characterized by severe, continuous, burning pain that often occurs in an extremity after injury or surgery.

Source: Grünenthal, December 20, 2016

Sublingual Cyclobenzaprine for PTSD

The FDA has granted breakthrough therapy status to cyclobenzaprine sublingual tablets (TNX-102 SL, Tonix Pharmaceuticals) for the treatment of patients with post-traumatic stress disorder. A phase 3 study is expected to begin in the first quarter of 2017.

Source: Tonix Pharmaceuticals, December 19, 2016

Orphan Drug Designations

MGD006 for AML

The FDA has granted an orphan drug designation to MGD006 (MacroGenics, Inc.), a dual-affinity retargeting molecule that recognizes both CD123 and CD3, for the investigational treatment of patients with acute myeloid leukemia (AML). MGD006 is being evaluated in the United States and Europe in a phase 1 dose-escalation study designed to determine the safety and tolerability of the molecule in patients with relapsed/refractory AML or myelodysplastic syndrome.

Source: MacroGenics, January 5, 2017

Emixustat for Stargardt Disease

Emixustat hydrochloride (Acucela Inc.) has received orphan drug status for the treatment of patients with Stargardt disease, the most common form of inherited juvenile macular degeneration.

The visual cycle is the process by which vitamin A is recycled in the eye; vitamin A is crucial to the visual process. Emixustat modulates the visual cycle by inhibiting a critical enzyme of this pathway, retinal pigment epithelium protein 65. Slowing the visual cycle reduces the availability of vitamin A derivatives (11-cis- and all-trans-retinal) to form precursors of A2E and related compounds. In animal models of Stargardt disease and retinal degeneration, emixustat was found to stop and reverse the accumulation of A2E and to preserve the integrity of the retina.

Source: Acucela, January 5, 2017

RG7916 for Spinal Muscular Atrophy

RG7916 (PTC Therapeutics) has received an FDA orphan drug designation for the treatment of patients with spinal muscular atrophy (SMA). SMA is a rare genetic disorder that results in neuromuscular disability beginning in infancy and is the leading inherited cause of mortality in infants and young children.

RG7916 is an oral small-molecule splicing modifier that directly targets the underlying molecular deficiency of SMA by modulating SMN2 splicing to increase the expression of stable full-length SMN proteins from the SMN2 gene. The compound is under investigation in two clinical studies: SUNFISH, a trial in childhood-onset (type 2/3) SMA patients, and FIREFISH, a trial in infant-onset (type 1) patients.

Source: PTC Therapeutics, January 6, 2017

CX-4945 for Cholangiocarcinoma

The FDA has granted an orphan drug designation to CX-4945 (Senhwa Biosciences) for the treatment of patients with cholangiocarcinoma. CX-4945 is a small-molecule drug that inhibits protein kinase CK2, which plays a key role in the DNA damage repair mechanisms of cancer cells. CX-4945 has demonstrated favorable safety, pharmacokinetic, and pharmacodynamic characteristics in the treatment of patients with advanced cholangiocarcinoma, according to the developer. This cancer is difficult to detect in its early stages, and the five-year survival rate is approximately 20%.

Source: Senhwa Biosciences, January 4, 2017

PIKA Rabies Vaccine

The FDA has granted an orphan drug designation for a polyinosinic–polycytidylic acid-based adjuvant (PIKA) rabies vaccine (Yisheng Biopharma) that is in phase 2 clinical development. The vaccine uses a proprietary Toll-like receptor-3 activation technology.

Source: Yisheng Biopharma, January 4, 2017

ES-3000 for AML

ES-3000 (Escend Pharmaceuticals) has received orphan drug status from the FDA for the treatment of patients with acute myeloid leukemia (AML). The FDA previously granted ES-3000 an orphan drug designation for the treatment of patients with chronic myeloid leukemia.

ES-3000 is an orally bioavailable small molecule that ablates leukemic stem cells by reducing beta-catenin expression. The Wnt/beta-catenin pathway is critical for the survival of cancer stem cells. ES-3000 is also in development for the treatment of patients with triple-negative breast cancer.

Source: Escend Pharmaceuticals, December 28, 2016

A004 for Retinitis Pigmentosa

The FDA has granted orphan drug status to A004 (MeiraGTx), an adeno-associated virus-mediated gene therapy product candidate containing the retinitis pigmentosa GTPase regulator (RPGR) gene for the treatment of patients with X-linked retinitis pigmentosa (XLRP).

More than 70% of XLRP cases and up to 20% of RP cases are caused by mutations in the RPGR gene. Males with XLRP caused by mutations in RPGR typically have night blindness in their first decade of life, followed by the progressive reduction of their visual field and the loss of visual acuity. By the end of their fourth decade, most patients are legally blind.

Source: MeiraGTx, December 20, 2016

Nintedanib for Mesothelioma

The FDA has granted an orphan drug designation to nintedanib (Boehringer Ingelheim) for the treatment of patients with mesothelioma. Nintedanib is an oral triple angiokinase inhibitor that simultaneously inhibits vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and fibroblast growth factor receptor signaling pathways. These three angiokinase receptors, which are not targeted by available therapies, play an important role in angiogenesis, tumor growth, and metastases.

Source: Boehringer Ingelheim, December 14, 2016

ABTL0812 for Pancreatic Cancer

ABTL0812 (Ability Pharmaceuticals) has received orphan drug status from the FDA for the treatment of patients with pancreatic cancer. The investigational compound, now in phase 2 clinical development, causes cell death by autophagy through the overexpression of TRIB3, an endogenous Akt regulator. It is a first-in-class, fully differentiated, oral, targeted anticancer compound inhibiting the PI3K/Akt/mTOR pathway without being a direct kinase inhibitor.

Source: Ability Pharmaceuticals, December 14, 2016

BHV-0223 for ALS

The FDA has granted orphan drug status to BHV-0223 (Biohaven Pharmaceutical Holding Company), an orally dissolving tablet being developed for the treatment of patients with amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease.

BHV-0223 is a sublingually absorbed dissolving tablet formulation of riluzole. It was designed to address some of the shortcomings associated with the solid oral dosage form of riluzole, which ALS patients have difficulty swallowing. Because BHV-0223 is systemically absorbed through the oral mucosa rather than through the gastrointestinal system, it is expected to eliminate the negative food effect associated with riluzole, to bypass first-pass metabolism, and to deliver effective doses of the drug at lower concentrations.

Source: Biohaven, December 9, 2016

Refusal to File Letter

Bupivacaine Implants for Pain

Innocoll has received a refusal to file letter from the FDA for Xaracoll (bupivacaine HCl collagen-matrix implants) for the treatment of postsurgical pain. After a preliminary review, the FDA determined that the application, which was submitted in October 2016, was not sufficiently complete to permit a substantive review. The FDA indicated, among other things, that Xaracoll should be characterized as a drug/device combination, which would require Innocoll to submit additional information. Xaracoll is a surgically implantable and bio-resorbable bupivacaine-collagen matrix that uses a proprietary collagen-based delivery technology.

Source: Innocoll, December 29, 2016

Complete Response Letter

Lutathera for Neuroendocrine Tumors

The FDA has issued a complete response letter (CRL) regarding the new drug application (NDA) for Lutathera (lutetium Lu 177 dotatate, Advanced Accelerator Applications), a Lu 177–labeled somatostatin analogue peptide, for the treatment of adults with gastroenteropancreatic neuroendocrine tumors. The CRL referred to issues with the format, traceability, uniformity, and completeness of the NETTER-1 and Erasmus clinical datasets that were preventing FDA reviewers from performing the required independent analysis of these clinical studies. In addition, the CRL requested analyses for gender, age, and racial subgroups, as well as other stratification factors and disease characteristics. A safety update on clinical and nonclinical studies was also requested. Finally, the CRL noted that observations made during inspections of manufacturing facilities supporting the NDA must be resolved before the NDA could be approved.

Source: Advanced Accelerator Applications, December 21, 2016


Acid-Suppressant Drugs Linked to GI Infections

In a population-based study conducted in Scotland, the use of commonly prescribed acid-suppressant medications (ASMs), such as proton pump inhibitors (PPIs), has been linked to an increased risk of intestinal infections with Clostridium difficile and Campylobacter bacteria, which can cause serious illness. The study involved 188,323 patients exposed to PPIs and H2 receptor antagonists (H2RAs) and 376,646 controls who were not exposed to ASMs between 1999 and 2013.

Compared with individuals in the community who did not take acid-suppressant drugs, those who did had 1.7-times and 3.7-times increased risks for C. difficile and Campylobacter infections, respectively. Among hospitalized patients, those using acid-suppressant medications had 1.4-times and 4.5-times increased risks, respectively. The adjusted hazard ratios for culture-positive diarrhea for the PPI-and H2RA-exposed cohort compared with the unexposed cohort were 2.72 for samples submitted from the community and 1.28 for samples submitted from hospitals.

Source: Wiley, January 5, 2017

Chantix Boxed Warning Dropped

The FDA has approved updates to the labeling for varenicline (Chantix, Pfizer), including removal of the boxed warning regarding serious neuropsychiatric events. The removal of the boxed warning was based on results from a pivotal smoking-cessation trial in patients with and without a history of psychiatric disorders, and was consistent with recent recommendations from the FDA’s Psychopharmacologic Drugs Advisory Committee and its Drug Safety and Risk Management Advisory Committee.

Additional labeling revisions based on the EAGLES trial include updates to the corresponding warning regarding neuropsychiatric safety and the addition of information on the superior efficacy of varenicline compared with bupropion or a transdermal nicotine patch.

Source: FDA, December 19, 2016

Anesthesia and Sedation in Children and Pregnant Women

The FDA has warned that repeated or lengthy use of general anesthetic and sedation drugs during surgeries or procedures in children younger than 3 years of age or in pregnant women during their third trimester may affect the development of children’s brains.

The agency has been investigating the potential adverse effects of general anesthetic and sedation drugs on children’s brain development since the first animal study on this topic was published in 1999. Health care providers are advised to balance the benefits of appropriate anesthesia in young children and pregnant women against the potential risks, especially for procedures that may last longer than three hours or if multiple procedures are required in children younger than 3 years of age.

Source: FDA, December 14, 2016

Pioglitazone and Bladder Cancer

As a result of an updated review, the FDA has concluded that the use of the type-2 diabetes medication pioglitazone (Takeda’s Actos, Actoplus Met, Actoplus Met XR, Duetact, and Oseni) may be linked to an increased risk of bladder cancer. The labels of pioglitazone-containing medications already include warnings about this risk, but the FDA has approved new label updates to describe additional study data.

Source: FDA, December 12, 2016


Contrave for Obesity

The phase 3, randomized, open-label IGNITE trial was designed to evaluate the use of Contrave (naltrexone and bupropion extended-release tablets, Orexigen Therapeutics) in combination with a commercially available lifestyle-intervention program compared with usual care in a “real-world” weight-loss setting. The results showed that treatment with Contrave, when used in a manner consistent with prescribing information in the United States, resulted in a significant reduction in body weight compared with usual care. After 26 weeks of treatment, participants in the Contrave group lost significantly more weight compared with the usual-care group (9.5% versus 0.9%, respectively; P < 0.0001).

Source: Orexigen Therapeutics, January 6, 2017

Humira Biosimilar

The comparative, confirmatory REFLECTIONS B538-02 study has met its primary endpoint by demonstrating the equivalent efficacy, as measured by the American College of Rheumatology 20% response rate at week 12, of PF-06410293 (Pfizer) and Humira (adalimumab, AbbVie), each administered with methotrexate, in patients with moderate-to-severe rheumatoid arthritis. PF-06410293, a monoclonal antibody, is being developed as a potential biosimilar to Humira, which is approved in the United States for multiple indications, including rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, pediatric Crohn’s disease, ulcerative colitis, plaque psoriasis, hidradenitis suppurativa, and uveitis.

Source: Pfizer, January 5, 2017

RHB-105 for H. Pylori Infection

RHB-105 (RedHill Biopharma) is an investigational fixed-dose oral combination therapy consisting of two antibiotics and a proton pump inhibitor in a single capsule. The product has a planned indication for the treatment of patients with Helicobacter pylori infection. A phase 3 study of RHB-105 has met its primary endpoint of superiority over the historical standard-of-care (SoC) eradication rate of 70% (P < 0.001). The study results demonstrated 89% efficacy in eradicating H. pylori infection with RHB-105. Subsequent open-label treatment with SoC therapies of patients in the placebo arm demonstrated a 63% eradication rate.

Source: RedHill Biopharma, January 4, 2017

Sollpura for Cystic Fibrosis

The SOLUTION trial of Sollpura (Anthera Pharmaceuticals), a nonporcine pancreatic enzyme replacement therapy (PERT), in cystic fibrosis patients with exocrine pancreatic insufficiency (EPI) narrowly missed its noninferiority margin versus a PERT comparator (Pancreaze, Janssen). Anthera expects to release data from the extension phase of this study during the first quarter of 2017. The company also plans to initiate another study of Sollupra in patients with EPI due to cystic fibrosis.

Source: Anthera Pharmaceuticals, December 27, 2016

Biosimilar Trastuzumab For Breast, Gastric Cancers

Phase 3 results have confirmed the efficacy, safety, and immunogenicity of MYL-1401O (Mylan/Biocon), a proposed biosimilar trastuzumab, in comparison with that of branded trastuzumab (Herceptin, Genentech). Herceptin is indicated for the treatment of patients with certain human epidermal growth factor receptor 2 (HER2)-positive breast and gastric cancers.

The HERITAGE trial was a double-blind, randomized study designed to compare MYL-1401O with Herceptin in patients with centrally confirmed, measurable HER2-positive metastatic breast cancer who had not received chemotherapy or trastuzumab for metastatic disease. The results showed an overall response rate of 69.6% for MYL-1401O compared with 64.0% for Herceptin at week 24 (the trial’s primary endpoint). Tumor progression, progression-free survival, and overall survival were not statistically different between the two groups at week 48.

Source: Mylan, December 27, 2016

Vadastuximab for AML

Seattle Genetics has received notice from the FDA that a clinical hold or partial clinical hold has been placed on several early-stage trials of vadastuximab talirine in subjects with acute myeloid leukemia (AML). The clinical holds were initiated to evaluate the potential risk of hepatotoxicity in patients who were treated with vadastuximab and who received allogeneic stem cell transplant either before or after treatment. Six patients were identified with hepatotoxicity, including several cases of veno-occlusive disease, with four deaths.

Vadastuximab talirine is an investigational antibody–drug conjugate targeted to the CD33 transmembrane receptor. CD33 is expressed on most AML and myelodysplastic syndrome blast cells. Vadastuximab is designed to be stable in the bloodstream and to release a cell-killing pyrrolobenzodiazepine dimer agent after internalization into CD33-expressing cells.

Source: Seattle Genetics, December 27, 2016

Emicizumab for Hemophilia

The primary endpoint has been reached in a pivotal phase 3 study evaluating prophylactic treatment with emicizumab (Chugai Pharmaceutical/Roche/Genentech) in patients 12 years of age or older with hemophilia A and inhibitors to factor VIII. The study showed a statistically significant reduction in the number of bleeds over time in patients treated with emicizumab prophylaxis compared with those receiving no prophylactic treatment.

The study also met all secondary endpoints, including a statistically significant reduction in the number of bleeds over time with emicizumab prophylaxis treatment in patients who had received prior bypassing-agent prophylaxis treatment.

Emicizumab is an investigational bispecific monoclonal antibody designed to bring together factors IXa and X—proteins required to activate the natural coagulation cascade and restore the blood-clotting process. Emicizumab is administered via a subcutaneous injection of a ready-to-use solution once weekly.

Source: Roche, December 22, 2016

Sotagliflozin for Type-1 Diabetes

A pivotal phase 3 trial of sotagliflozin (Lexicon Pharmaceuticals) has met its primary endpoint, demonstrating a statistically significant reduction in hemoglobin A1C (HbA1C) at 24 weeks in patients with type-1 diabetes receiving optimized insulin therapy. Patients treated with sotagliflozin had mean HbA1C reductions from baseline of 0.39% with a 200-mg once-daily dosage of sotagliflozin (P < 0.001) and 0.37% with a 400-mg once-daily dosage of sotagliflozin (P < 0.001) compared with a reduction of 0.03% with placebo after 24 weeks of treatment.

Sotagliflozin is a first-in-class, oral dual inhibitor of two proteins responsible for glucose regulation—sodium-glucose cotransporter types 1 and 2 (SGLT1 and SGLT2). SGLT1 is the primary transporter for absorption of glucose and galactose in the gastrointestinal tract, and SGLT2 is primarily responsible for glucose reabsorption by the kidneys.

Source: Lexicon Pharmaceuticals, December 21, 2016

Plazomicin for Infections Resistant to Multiple Drugs

Plazomicin (Achaogen, Inc.), an antibiotic being developed to fight multidrug-resistant bacterial infections, has met the primary objective of noninferiority compared with meropenem in a phase 3 registration trial in patients with complicated urinary tract infections and acute pyelonephritis.

In addition, in a phase 3 trial in patients with serious infections due to carbapenem-resistant Enterobacteriaceae (CRE), a lower rate of mortality or serious disease-related complications was observed for plazomicin compared with colistin, one of the few remaining antibiotics for the treatment of infections due to CRE. Achaogen plans to submit a new drug application for plazomicin to the FDA in the second half of 2017.

Source: Achaogen, December 12, 2016

Edurant/Tivicay for HIV

Two phase 3 studies designed to evaluate the efficacy, safety, and tolerability of switching virologically suppressed patients from a three- or four-drug antiretroviral regimen to the two-drug regimen of rilpivirine (Edurant, Janssen) and dolutegravir (Tivicay, ViiV Healthcare) have met the primary endpoint of noninferiority at week 48.

In both studies, the subjects achieved plasma human immunodeficiency virus-1 (HIV-1) RNA levels of less than 50 copies/mL. Regulatory submissions for the investigational two-drug regimen of rilpivirine and dolutegravir as a single tablet are expected in 2017.

Rilpivirine is a prescription HIV medication that is used with other antiretroviral drugs to treat patients with HIV-1 infection who have never received HIV medications and who have a viral load of no more than 100,000 copies/mL. Dolutegravir is an HIV-1 integrase strand transfer inhibitor indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 30 kg.

Source: Janssen, December 19, 2016

Pegpleranib for AMD

Two pivotal phase 3 studies evaluating the safety and efficacy of pegpleranib (Novartis) in combination with ranibizumab (Lucentis, Genentech) for the treatment of patients with neovascular age-related macular degeneration did not meet the primary endpoint of superiority for the pegpleranib/ranibizumab combination therapy over ranibizumab monotherapy.

At month 12, patients in the pegpleranib/ranibizumab groups showed a 10.74-letter improvement in best corrected visual acuity (BCVA) compared with a 9.82-letter improvement with ranibizumab alone in study OPH1002. Similarly, the pegpleranib/ranibizumab combination treatment groups showed a 9.91-letter BCVA improvement compared with a 9.82-letter improvement with ranibizumab alone in study OPH1003.

Pegpleranib is a 32-mer pegylated DNA aptamer that selectively binds to platelet-derived growth factor (PDGF)-BB and PDGF-AB homo- and heterodimers, respectively, thereby disrupting the interaction with their cognate tyrosine kinase receptors.

Source: Novartis, December 12, 2016

Plecanatide for IBS With Constipation

Positive results have been reported from the first of two pivotal phase 3 trials evaluating the efficacy and safety of plecanatide (Synergy Pharmaceuticals), an investigational once-daily, orally administered compound, in adults with irritable bowel syndrome with constipation (IBS-C). Both doses of plecanatide (3 mg and 6 mg) met the study’s primary endpoint, showing statistical significance in the percentage of patients who were overall responders compared with placebo during the 12-week treatment period (21.5% in the 3-mg group and 24.0% in the 6-mg group compared with 14.2% in the placebo group; P = 0.009 for 3 mg and P < 0.001 for 6 mg).

Plecanatide is a peptide made up of 16 amino acids. With the exception of a single amino acid substitution, it is identical to uroguanylin, an endogenous human gastrointestinal peptide that targets receptors in the proximal small intestine.

Source: Synergy Pharmaceuticals, December 9, 2016

Solanezumab for Alzheimer’s

The monoclonal antibody solanezumab (Eli Lilly) failed to meet the primary endpoint in a pivotal phase 3 study involving patients with mild dementia due to Alzheimer’s disease, and Lilly announced that it will not pursue regulatory submissions of the medication. Patients treated with solanezumab did not experience a statistically significant slowing in cognitive decline compared with patients given placebo. This finding represented an 11% reduction in decline (P = 0.095), as measured by the Alzheimer’s Disease Assessment Scale–Cognitive subscale.

Source: Eli Lilly, December 8, 2016

Cimzia for Plaque Psoriasis

UCB and Dermira, Inc., have announced positive results from the phase 3, placebo-controlled CIMPASI-1 trial, which evaluated the efficacy and safety of certolizumab pegol (Cimzia) in adults with moderate-to-severe chronic plaque psoriasis.

A total of 234 patients were randomly assigned to three dosing arms: 400 mg every two weeks (n = 88); 400 mg at weeks 0, 2, and 4 followed by 200 mg every two weeks (n = 95); or placebo every two weeks (n = 51). At week 16, the response rate for patients who achieved 75% or greater disease improvement from baseline, as measured by the Psoriasis Area and Severity Index, was 75.8% for patients receiving the 400-mg dose every two weeks and 66.5% for patients receiving the 200-mg dose every two weeks, compared with 6.5% for patients receiving placebo. The response rate for patients achieving at least a two-point improvement to a final score of clear or almost clear skin on the Physician’s Global Assessment scale at week 16 was 57.9% for the 400-mg dose-treated patients and 47.0% for the 200-mg dose-treated patients, compared with 4.2% for the patients receiving placebo.

Source: UCB, December 8, 2016

Actimmune for Friedreich’s Ataxia

A phase 3 trial evaluating Actimmune (interferon gamma-1b, Horizon Pharma) for the treatment of patients with Friedreich’s ataxia (FA) failed to meet its primary endpoint of a statistically significant change from baseline in the modified FA Rating Scale at 26 weeks compared with placebo. FA is a degenerative neuromuscular disorder that affects approximately 4,000 to 6,000 people in the United States. There are no approved treatments for the disease.

Actimmune is currently indicated to reduce the frequency and severity of serious infections associated with chronic granulomatous disease, a genetic disorder that affects the functioning of some cells of the immune system. Actimmune is also indicated to delay the time to disease progression in patients with severe, malignant osteopetrosis, a genetic disorder that affects normal bone formation.

Source: Horizon Pharma, December 8, 2016

IDP-118 for Plaque Psoriasis

Positive results have been reported from a phase 3, double-blind, randomized study that compared IDP-118 lotion (halobetasol propionate and tazarotene, Valeant Pharmaceuticals) with vehicle in 215 patients with moderate-to-severe plaque psoriasis.

After 12 weeks of treatment, IDP-118 was significantly more effective than vehicle, with a 45.3% success rate (P < 0.001). This pivotal study was preceded by a phase 2 trial in which IDP-118 was clinically superior to halobetasol propionate and tazarotene, with a success rate of 52.5%.

Source: Valeant, December 8, 2016


Aptima HIV-1 Assay

The FDA has approved the Aptima HIV-1 Quant assay (Hologic, Inc.) for monitoring the viral load in patients infected with human immunodeficiency virus 1 (HIV-1). The nucleic acid amplification test is designed for the quantitative detection of RNA from HIV in plasma specimens. The assay is not approved for HIV-1 diagnosis in the United States.

Source: Hologic, January 3, 2017

AeroForm Tissue Expander For Breast Reconstruction

The FDA has allowed the marketing of the AeroForm device (AirXpanders), a system for soft-tissue expansion in two-stage breast reconstruction after mastectomy and in the treatment of underdeveloped breasts and soft-tissue deformities. The patient uses a dose controller to independently inflate the expander.

The AeroForm device differs from available saline-filled tissue expanders, which are expanded by the surgeon, who uses a needle to pierce the skin and inject saline into the expander through a port or injection area. The AeroForm expander is filled with air; there is no need for a needle, and the patient has control over slowly expanding the device at home.

Source: AirXpanders, December 20, 2016

Continuous Glucose Monitoring System

The FDA has expanded the approved use of the Dexcom G5 mobile continuous glucose monitoring system (Dexcom, Inc.) to allow the replacement of finger-stick blood glucose testing for treatment decisions in diabetes patients 2 years of age and older. This is the first FDA-approved continuous glucose monitoring system that can be used to make diabetes treatment decisions without confirmation with a traditional finger-stick test. The system was previously approved to complement, not replace, finger-stick testing for diabetes treatment decisions.

Source: Dexcom, December 20, 2016

OneTouch Vibe Plus Insulin Pump

The FDA has cleared the OneTouch Vibe Plus insulin pump and continuous glucose monitoring (CGM) system for the treatment of diabetes patients 2 years of age and older. The OneTouch Vibe Plus (Animas Corporation) is the only insulin pump integrated with Dexcom G5 (Dexcom, Inc.) mobile CGM technology, combining insulin dosing technology from Animas with the CGM sensing technology from Dexcom. The system allows patients to see their glucose reading at all times, either on their pumps or by using the Dexcom G5 app on their smartphones, and to deliver the precise amounts of insulin they need from the pumps.

Source: Animas, December 20, 2016

New MRSA Test

The FDA has given the green light to Xpert MRSA NxG (Cepheid International), a new infection-control test for methicillin-resistant Staphylococcus aureus. The molecular assay provides actionable results in approximately one hour. From one to 80 Xpert assays can be performed at the same time. As a result, the test may be used by customers of all sizes—from point-of-care settings to reference laboratories, according to Cepheid.

Source: Cepheid International, December 19, 2016

Micro-Ultrasound System For Prostate Imaging

The ExactVu micro-ultrasound system (Exact Imaging) has received 510(k) clearance from the FDA for prostate microimaging. With resolution down to 70 microns (0.07 of a millimeter), the system provides a 300% improvement in imaging resolution compared with traditional standard-of-care urologic ultrasound systems, according to the manufacturer.

Source: Exact Imaging, December 9, 2016