FDA News, Week of Aug 17, 2015

Summary : FDA’s collaborative efforts with ex-US Agencies to harmonize Device dossier formats for registrational submissions to accelerate global registration of devices

http://www.imdrf.org/documents/documents.asp?source=govdelivery&utm_medium=email&utm_source=govdelivery

FDA approved

Addyi (flibanserin) (Sprout Pharmaceuticals, Raleigh, NC)

serotonin 1A receptor agonist and a serotonin 2A receptor antagonist

Indication: Generalized hypoactive sexual desire disorder (HSDD) as characterized by low sexual desire that causes marked distress or interpersonal difficulty and is NOT due to:

  • A co-existing medical or psychiatric condition,
  • Problems within the relationship, or
  • The effects of a medication or other drug substance.

Efficacy:

  • Three 24week, randomized, double-blind, placebo-controlled trials (Studies 1, 2, and 3).
  • co-primary efficacy endpoints, one for satisfying sexual events (SSEs) and the other for sexual desire:
  • Number of satisfying sexual events (per 28 days), P<0.01 – p<0.0001
  • Desire (measured by e-Diary), Female Sexual Function Index, Female Sexual Distress Scale-Revised
  • About 10 percent more Addyi-treated patients than placebo-treated patients reported meaningful improvements in satisfying sexual events, sexual desire or distress

Safety: Boxed warning and REMS

  • Severely low blood pressure (hypotension) and loss of consciousness (syncope).
  • Risks increased and more severe when patients drink alcohol or take Addyi with moderate or strong CYP3A4 inhibitors
  • BOXED WARNING :  Risks of severe hypotension and syncope in patients who drink alcohol during treatment with Addyi, in those who also use moderate or strong CYP3A4 inhibitors, and in those who have liver impairment

Stringent Risk Evaluation and Mitigation Strategy (REMS) – Elements to Assure Safe Use  (ETASU)

Certification of HCPs, Pharmacy enrollment tracking

Mitigate the increased risk of hypotension and syncope due to an interaction with alcohol by:

  • Ensuring prescribers and pharmacists are educate and need to counsel patients about this risk.
  • Informing patients of the increased risk

Summary:

Approval viewed as controversial with high probabilities of off-label use and unanticipated safety issues vs. unmet need and effectiveness. FDA’s proposed mitigation by Boxed Warning and stringent (REMS)

FDA ‘s approval part of Patient-Focused Drug Development – scientific workshop on female sexual dysfunction on October 27 and October 28, 2014, to solicit patient perspectives

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New FDA Guidances on Unique Drug Development Topics

botanical

  • unique nature of botanical drugs
  • regulatory policies differ from those for synthetic, semi-synthetic, chemically modified drugs
  • OTC, IND, NDA requirements provided
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM458484.pdf?source=govdelivery&utm_medium=email&utm_source=govdelivery

rare diseasesRARE DISEASE  affects < 200,000 persons in US; most  affect far fewer persons. Guidance addresses  important aspects of drug development:

  • Disease’s natural history
  • Pathophysiology of disease and drug’s proposed mechanism of action
  •  Nonclinical pharmacotoxicology considerations
  • Reliable endpoints and outcome assessment
  • Standard of evidence to establish safety and effectiveness
  • Drug manufacturing considerations during drug development
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM458485.pdf?source=govdelivery&utm_medium=email&utm_source=govdelivery

Parkinson’s Disease : New Drugs in Development

The loss of dopamine-producing cells in the brain is an underlying issue in Parkinson’s disease.

Currently approved or in R&D medicines for Parkinson’s disease treat the symptoms of the disease, such as mobility problems and tremors, but do not replace lost nerve cells or halt the progression of the disease itself.

Several drugs in development are disease-modifying therapies focused on protecting brain cells in an attempt to halt disease progression, or treatments aimed at generating new cells or repairing damaged nerve cells.

Product Name Sponsor Indication Development Phase*
AAV-hAADC

gene therapy

Genzyme

Cambridge, MA

University of California San Francisco

San Francisco, CA

Voyager Therapeutics

Cambridge, MA

Parkinson’s disease Phase I

http://www.voyagertherapeutics.com

Duodopa®

levodopa/carbidopa intestinal gel

ORPHAN DRUG

AbbVie

North Chicago, IL

advanced Parkinson’s disease

(Fast Track)

application submitted

http://www.abbvie.com

AAV2 GDNF

gene therapy

UniQure

Amsterdam, Netherlands

University of California San Francisco

San Francisco, CA

Parkinson’s disease Phase I

http://www.uniqure.com

Ampyra®

dalfampridine

Acorda Therapeutics

Ardsley, NY

University of Miami

Miami, FL

Parkinson’s disease

(improve gait)

Phase I/II

http://www.acorda.com

AVE8112

(PDE4 inhibitor

The Michael J. Fox Foundation for

Parkinson’s Research

New York, NY

Sano_ US

Bridgewater, NJ

Parkinson’s disease Phase I

http://www.michaeljfox.org

AZD3241

(myeloper-oxidase [MPO]

inhibitor)

AstraZeneca

Wilmington, DE

Parkinson’s disease Phase II

http://www.astrazeneca.com

BIA 9-1067

(opicapone)

Bial

Coronado, Portugal

Parkinson’s disease Phase I completed

http://www.bial.com

DopaFuse

levodopa continuous infusion

therapy

SynAgile

Piedmont, CA

Parkinson’s disease Phase I

http://www.synagile.com

GM608 Genervon Biopharmaceuticals

Pasadena, CA

Parkinson’s disease Phase II

http://www.genervon.com

HT-1067

(MOA-B inhibitor

Dart NeuroScience

San Diego, CA

Parkinson’s disease Phase I

http://www.dartneuroscience.com

IPX203 Impax Pharmaceuticals Hayward, CA Parkinson’s disease Phase II http://www.impaxpharma.com
istradefylline (KW-6002) Kyowa Hakko Kirin Pharma Princeton, NJ severe Parkinson’s disease Phase III http://www.kyowa-kirin-pharma.com
levodopa inhalation (CVT-301) Civitas Therapeutics Chelsea, MA Parkinson’s disease (adjunctive therapy) Phase II http://www.civitastherapeutics.com
LY03003 (rotigotine extended-release microsphere formulation) Luye America Pharmaceuticals Princeton, NJ Parkinson’s disease (early-stage disease) Phase I http://www.luye.cn/en/
OS-320 (levodopa/carbidopa) Osmotica Pharmaceutical Wilmington, NC Parkinson’s disease Phase III http://www.osmotica.com
P2B001 (pramipexole/rasagiline ­ xed-dose combination) Pharma Two B Rehovot, Israel Parkinson’s disease (early-stage disease) Phase II http://www.pharma2b.com
Phosphen® R-phenserine QR Pharma Berwyn, PA Parkinson’s disease Phase II http://www.qrpharma.com
Rytary™ levodopa/carbidopa extended release Impax Pharmaceuticals Hayward, CA idiopathic Parkinson’s disease application submitted http://www.impaxpharma.com
safinamide Newron Pharmaceuticals Bresso, Italy early-stage Parkinson’s disease (adjunctive therapy)

——————————— late-stage and mid-stage Parkinson’s disease (adjunctive therapy)

Phase III http://www.newron.com

———————————— Phase III http://www.newron.com

tozadenant (SYN-115) Biotie Therapies South San Francisco, CA UCB Brussels, Belgium Parkinson’s disease (adjunctive therapy) Phase II/III http://www.biotie.com http://www.ucb.com
V81444 Vernalis Winnersh, United Kingdom Parkinson’s disease Phase I/II http://www.vernalis.com
vatiquinone Edison Pharmaceuticals Mountain View, CA Parkinson’s disease Phase II http://www.edisonpharma.com
XP21279 XenoPort Santa Clara, CA Parkinson’s disease Phase II http://www.xenoport.com
Florbenazine (18F-AV-133) Eli Lilly Indianapolis, IN Parkinson’s disease (diagnosis) Phase II

http://www.lilly.com

NAV5001

(123-I labeled imaging agent)

Navidea Biopharmaceuticals Dublin, OH Parkinsonian disorders (diagnosis) Phase III http://www.navidea.com
NuroPro® neurotrophic factor companion diagnostic Amarantus BioScience San Francisco, CA Parkinson’s disease (diagnosis) Phase I http://www.amarantus.com
Parkinson’s Disease—Related Conditions
ADS-5102 (amantadine controlled release) Adamas Pharmaceuticals Emeryville, CA levodopa-induced dyskinesia Phase II/III http://www.adamaspharma.com
AQW051 (alpha7 nicotinic receptor) Novartis Pharmaceuticals East Hanover, NJ Levodopa-induced dyskinesia Phase II completed http://www.novartis.com
AVP-923 (dextromethorphan/quinidine) Avanir Pharmaceuticals Aliso Viejo, CA Levodopa-induced dyskinesia Phase II

http://www.avanir.com

camicinal (motilin receptor agonist) GlaxoSmithKline , PA gastroparesis in Parkinson’s disease Phase II http://www.gsk.com
dipraglurant-IR (ADX48621) Addex Therapeutics Geneva, Switzerland Levodopa-induced dyskinesia Phase II http://www.addextherapeutics.com
eltoprazine Amarantus BioScience San Francisco, CA Levodopa-induced dyskinesia Phase II

http://www.amarantus.com


		

FDA News, Week of Aug 10, 2015

FDA Voice

precision medicine

Advancing precision medicine by enabling a collaborative informatics community

  •  FDA proposing an informatics community ‘precisionFDA .’ in support of President Obama’s Precision Medicine Initiative
  • Use of next generation sequencing (NGS) to determine future risk of disease, behavior, or treatment choices
  • Novel regulatory framework – using shared databases to ease regulatory burden

Storyline : Innovative and collaborative proposals along with novel regulatory pathways being proposed by the FDA to develop individualized treatment options

http://blogs.fda.gov/fdavoice/index.php/2015/08/advancing-precision-medicine-by-enabling-a-collaborative-informatics-community/?source=govdelivery&utm_medium=email&utm_source=govdelivery

Homage:

Frances Oldham Kelsey, Ph.D., M.D.: A Pioneer in Public Health and Protection of Patients

kelseyJoined FDA in 1960 as a medical officer

Refused to approve thalidomide because of inadequate evidence about its safety

Spared the tragic birth defects and deaths experienced by patients in those countries where thalidomide was available

Kefauver-Harris Drug Amendments became law in 1962 – mandating “substantial evidence” of a drug’s effectiveness + Safety

Revered as a leader in drug safety and the protection of patients

http://blogs.fda.gov/fdavoice/index.php/2015/08/frances-oldham-kelsey-ph-d-m-d-a-pioneer-in-public-health-and-protection-of-patients/

FDA approved

ORBERA™ Intragastric Balloon System (Apollo Endosurgery, Inc. Austin, TX)

orbera

Reg pathway: PMA

Ex-US approvals : Several, since the 1990s. PMA supported by safety data from clinical product surveillance and studies in Australia and France

Indications for Use: Adjunct to weight reduction for adults with obesity with Body Mass Index (BMI) of ≥ 30 and ≤ 40 kg/m2 and is to be used in conjunction with a long-term supervised diet and behavior modification program designed to increase the possibility of significant long-term weight loss and maintenance of that weight loss.

Description:  Non-surgical aid, soft, smooth silicone elastomer balloon that is placed in the stomach endoscopically and filled with saline, causing it to expand into a spherical shape. The filled balloon is designed to occupy space and move freely within the stomach (Figure). Self-sealing valve permits detachment of the balloon from external catheters used during the ORBERA™ placement procedure

Effectiveness: 

  • Single pivotal study (IB-005), n= 448
  • Two co-primary endpoints : Percent excess weight loss (%EWL) at Month 9, and Percent subjects with ‘significantly greater weight loss’ (≥ 15% EWL).

  • Did not meet prespecified EWL target; however treatment group showed significant Total Body Weight Loss (TBWL, 5.7% over control) at month 9.
  • Met second co-primary endpoint with 45.6% treated subjects achieving at least 15% EWL over control
  •  Treated group lost significantly more weight than the control group over the study and was able to maintained significant weight loss through Month 12; 6 months after removal of the device.

Safety:

  • No unanticipated adverse device effects or deaths; 5% Serious Adverse events due to device intolerance

Benefit/Risk:

  • Probable benefits of demonstrated statistically significant weight loss over the control group at device removal (6 months); maintenance of 70% of the weight loss out to 12 months
  • Risks for patients developing adverse events related to the device
  • Limited less invasive obesity treatment options currently available.  ORBERA  can offer patients significant weight loss, with low risk,  when used in conjunction with a diet and exercise program.

 

Malaria Vaccine: Current Status

malaria

Malaria occurs in nearly 100 countries worldwide, exacting a huge toll on human health and imposing a heavy social and economic burden in developing countries, particularly in Sub-Saharan Africa and South Asia. An estimated 207 million people suffered from the disease in 2012, and about 627,000 died. About 90 percent of the deaths were in Sub-Saharan Africa, and 77 percent were among children under age 5.

It is transmitted among humans by female mosquitoes of the genus Anopheles. Female mosquitoes take blood meals to carry out egg production, and such blood meals are the link between the human and the mosquito hosts in the parasite life cycle.  The parasite Plasmodium, a single-celled organism that has multiple life stages and requires more than one host for its survival. Five species of the parasite cause disease in humans – Plasmodium falciparum, P. vivax, P. ovale, P. malariae, and P. knowlelsi. Plasmodium falciparum is the most dangerous strain in humans and the target of most scientific research today.

Malaria symptoms are high fever, chills, flu-like symptoms, and severe anemia. These symptoms can be especially dangerous for pregnant women and young children who are experiencing the disease for the first time. Severe malaria can cause lifelong intellectual disabilities in children, and malaria’s economic impact is estimated to cost billions of dollars in lost productivity every year.

Calling the Ebola epidemic a “critical moment in the history of global health,” Bill Gates, Co-chair of the Bill & Melinda Gates Foundation (PATH Malaria Vaccine Initiative), urged greater investment in scientific innovation to ensure that the world stays ahead of rapidly evolving disease threats such as drug-resistant malaria and dengue fever.

Addressing the annual meeting of the American Society of Tropical Medicine and Hygiene, Gates announced that the foundation is committing more than $500 million to reduce the burden of malaria, pneumonia, diarrheal diseases, and an array of parasitic infections that are leading causes of death and disability in developing countries. Gates also announced that the foundation has boosted its annual funding for malaria by 30 percent, and he laid out a vision for how malaria can be eradicated by the middle of the 21st century.

World’s first malaria vaccine, backed by Bill Gates, received a green light for future use in babies in sub-Saharan Africa. GlaxoSmithKline worked with the PATH Malaria Vaccine Initiative to develop the vaccine, which was called RTS,S when it was experimental and which now has the brand name Mosquirix. The European Medicines Agency has OK’d it for use in children 6 weeks to 17 months old.Jul 24, 2015.

Mosquirix. is the most advanced vaccine candidate against the most deadly form of human malaria, Plasmodium falciparum. A Phase III trial began in May 2009 and has completed enrolment with 15 460 children in the following seven countries in sub-Saharan Africa: Burkina Faso, Gabon, Ghana, Kenya, Malawi, Mozambique, and the United Republic of Tanzania. The World Health Organization lists malaria as the fifth biggest killer in sub-Saharan Africa.

There are two age groups in the trial: 1) children aged 5-17 months at first dose receiving only the RTS,S/AS01 vaccine; and 2) children aged 6-12 weeks at first dose who receive the same malaria vaccine co-administered with pentavalent vaccines in the routine immunization schedule. Both groups receive 3 doses of Mosquirix. vaccine at 1 month intervals.

The final Phase III results were published in April 2015. The vaccine will be evaluated as an addition to, not a replacement for, existing preventive, diagnostic and treatment measures. The need for long-lasting insecticidal nets, rapid diagnostic tests and artemisinin-based combination therapies will continue if Mosquirix. becomes available and is used. It prevented a substantial number of cases of clinical malaria over a 3–4 year period in young infants and children when administered with or without a booster dose. Efficacy was enhanced by the administration of a booster dose in both age categories. Thus, the vaccine has the potential to make a substantial contribution to malaria control when used in combination with other effective control measures, especially in areas of high transmission.

STORYLINE:  Drug-resistant malaria is viewed as an epidemic in developing countries. Vaccines being developed and approved to curb the spread of malaria. Vaccines will complement the existing therapies and preventive measures.

malaria vaccine development

FDA News, Week of Aug 3, 2015

FDA approved

FDA Approves 3D printed tablets (Aprecia Pharmaceuticals, Blue Ash, OH)

 zipdoseFDA has approved SPRITAM® levetiracetam for oral use as a prescription adjunctive therapy in the treatment of partial onset seizures, myoclonic seizures and primary generalized tonic-clonic seizures in adults and children with epilepsy.

SPRITAM utilizes Aprecia’s proprietary ZipDose® Technology platform, that uses three-dimensional printing (3DP) to produce a porous formulation that rapidly disintegrates with a sip of liquid.1 While 3DP has been used previously to manufacture medical devices, this approval marks the first time a drug product manufactured with this technology has been approved by the FDA.

ZipDose® Technology product candidates are intended to improve the patient experience and help increase adherence by being designed to1:

  • Rapidly disintegrate in less than 10 seconds—a previously unachievable rate for high-dose formulations (based on demonstrator development testing)
  • Offer a wider range of taste-masking capabilities than were previously possible

FDA Approves DELTOID Injection Site for Abilify Maintena® (aripiprazole) for extended-release injectable suspension in the Treatment of Schizophrenia (Otsuka Pharmaceuticals, Princeton, NJ)

MaintenaPatients being treated for schizophrenia now have a new administration site option 

Approval based on data demonstrating  comparable pharmacokinetics, tolerability and safety of deltoid vs gluteal administration

Drug Safety Podcasts for Healthcare Professionals

CapturesafetyDivision of Drug Information has posted new Drug Safety Podcasts for Healthcare Professionals. Click on the following links to read transcripts and listen to podcasts.

.

Vaccine candidate shows efficacy against Dengue

dengue

Dengue is caused by four distinct virus serotypes transmitted by mosquitoes. It is a threat to nearly half of the world’s population. Currently, there is no specific treatment available for dengue. It is a health priority in many countries of Latin America and Asia where epidemics occur regularly.

The yellow fever mosquito can spread the dengue fever and yellow fever viruses, and other diseases. The mosquito is a small, dark mosquito of approximately 4 to 7 millimeters with typical white markings on the legs and a marking of the form of a lyre on the thorax. Dengue is transmitted by a mosquito bite that could cause infection of one of four dengue virus (DENV) serotypes, known as DENV1-4.

Symptoms of dengue include fever, severe headache, joint pain, muscle and bone pain, severe pain behind the eyes and mild bleeding – such as nose bleed. A more severe form of the virus is known as dengue hemorrhagic fever, characterized by prolonged fever, abdominal pain, persistent vomiting, bleeding and breathing problems. According to the World Health Organization, more than 22,000 people worldwide die from dengue each year, the majority of whom are children. Dengue is underreported because the disease is often misdiagnosed due to a large spectrum of clinical symptoms from mild non-specific illness to life threatening complications and because of the limitations of the surveillance systems.
Sanofi Pasteur’s dengue vaccine candidate is the most clinically and industrially advanced vaccine candidate in development. Two pivotal Phase III efficacy studies involved more than 31,000 volunteers from Asia (Indonesia, Malaysia, the Philippines, Thailand and Vietnam) and Latin America (Brazil, Colombia, Honduras, Mexico and Puerto Rico). The Phase III trials provided pivotal data on efficacy, safety, and immunogenicity of the vaccine candidate in a broad population and different epidemiological environments and assess the potential public health impact of the vaccine on the disease burden.
“The results of this first phase III study show the potential of the vaccine to have a significant impact on public health,” commented Dr. Maria Rosario Capeding, study principal investigator, Research Institute for Tropical Medicine, the Philippines. “The threat of severe dengue disease creates fear in the community. The vaccine’s impact on preventing dengue hemorrhagic fever is noteworthy. A vaccine that is able to avoid the personal suffering and reduce this significant health burden would change the lives of millions.”

“The high efficacy observed against severe dengue and the reduction of hospitalization by two thirds is an extremely important public health outcome. Furthermore this dengue vaccine continues to meet the highest safety expectations, which is very reassuring,” commented Professor Duane Gubler, Professor and Founding Director of the Signature Research Program on Emerging Infectious Diseases, Duke-NUS Graduate Medical School, Singapore, and Chairman of the Partnership for Dengue Control.

Pooled vaccine efficacy against dengue of any severity and any serotype from the efficacy surveillance phase among participants who were 9 years of age or older was 65.6%; pooled vaccine efficacies for serotype-specific dengue were all higher than the nonpooled vaccine efficacies. On the basis of a limited number of participants in the immunogenicity subgroups, pooled analyses of data from participants who were 9 years of age or older showed that the vaccine efficacies were 81.9% (95% CI, 67.2 to 90.0) among seropositive participants and 52.5% (95% CI, 5.9 to 76.1) among seronegative participants

Efficacy and Long-Term Safety of a Dengue Vaccine in Regions of Endemic Disease” study report can be found in the New England J Med link (July 27, 2015) http://www.nejm.org/doi/full/10.1056/NEJMoa1506223

Public Meeting on Patient-Focused Drug Development for Nontuberculous Mycobacterial Lung Infections

pt focus dd

On October 15, 2015, FDA is conducting a public meeting on Patient-Focused Drug Development for Nontuberculous Mycobacterial Lung Infections. FDA is interested in obtaining patients’ perspectives on the impact of Nontuberculous Mycobacterial Lung Infections on daily life and patient views on treatment approaches.

In the afternoon, FDA will hold a workshop and provide information for and gain perspective from patients and patient advocacy organizations, health care providers, academic experts, and industry on various aspects of clinical development of drug products intended to treat NTM lung infections.

To register : http://www.fda.gov/Drugs/NewsEvents/ucm453877.htm

FDA News, Week of July 27th

FDA approved

Medrobotics Flex System (Medrobotics Corporation, Raynham,  MA – a Carnegie Mellon Unv. spinoff)

First robot-assisted surgical platform with a unique, flexible, robotic scope that precisely moves through the body’s natural twists and turns

medroboticsReg Pathway : 510 K ; has received EU CE mark.

Indication for use:  Transoral Procedures in the Mouth and Throat; for use in head and neck surgeries

Effectiveness : A flexible endoscopic system that enables surgeons to access and visualize hard-to-reach anatomical locations, the system extends the benefits of minimally invasive surgery — shorter hospital stays and recovery times — to a broader population of patients

ReShape™ Integrated Dual Balloon Systemn  (ReShape Medical, Inc., San Clemente, CA)

balloonReg Pathway : PMA

Indication for Use : Weight reduction when used in conjunction with diet and exercise, in obese patients with a Body Mass Index (BMI) of 30 – 40 kg/m2 and one or more obesity-related comorbid conditions. It is indicated for use in adult patients who have failed weight reduction with diet and exercise alone.

Effectiveness:

  • Feasibility Study : 30 subjects, ReShape Duo Balloon (Treatment Group) vs diet/ exercise  (Control Group). ReShape Duo Balloon treated subjects had a mean weight loss greater than that of the control subjects at every point of follow-up.
  •  Pivotal REDUCE Study: 300 obese subjects, ReShape plus a diet/exercise (Treatment) vs. endoscopic procedure plus a diet/exercise (Active Sham) . ReShape group had 13.0% greater Excess Weight Loss vs sham group and the Responder rate (% weight loss >25%) of 49%.  However, weight maintenance for 24 weeks after device removal in the Treatment Group was not met consistently.

 Safety: No unanticipated adverse device effects. Higher nausea, vomiting, and abdominal pain with ReShape. Most significant concern –  gastric ulcerations and gastric bleeding

Benefit/Risk :

  • Probable benefits of demonstration of moderate weight loss with the device and some weight lost maintenance in some subjects 24 weeks after the device was removed.
  • Most worrisome risk is the development of gastric ulcerations.
  • Limited options currently available. ReShape better than diet and; however,  substantially less effective than approved gastric banding or other surgical interventions.
  • ReShape has potential for moderate short-term weight loss with an acceptable safety profile for subjects with mild to moderate obesity who have failed other means for conservative weight loss.

http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm456293.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery

PRALUENT (Alirocumab, Sanofi-Aventis Bridgewater, NJ and Regeneron Pharmaceuticals Inc., Tarrytown, NY)

Alirocumab is a human monoclonal antibody (IgG1 isotype) that targets proprotein convertase subtilisin kexin type 9 (PCSK9). To be administered subcutaneously once every 2 weeks

 Indication : indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease, who require additional lowering of LDL-C.

Efficacy:

Five double-blind placebo-controlled trials, 3499 patients

  • Study 1 : At week 24, the treatment difference between PRALUENT and placebo in mean LDL-C percent change was -58% (p: <0.0001).
  • Study 2 : At week 12, the mean percent change from baseline in LDL-C was -45% with PRALUENT compared to 1% with placebo,
  • Study 3 & 4 : At week 12, the treatment difference between PRALUENT 75 mg Q2W and placebo in mean LDL-C percent change was -48%
  • Study 5 : At week 24, the mean percent change from baseline in LDL-C was -43% with PRALUENT and -7% with placebo, and the treatment difference between PRALUENT and placebo in mean LDL-C percent change was -36% (p- <0.0001).The effect of PRALUENT on cardiovascular morbidity and mortality has not been determined

Safety : Hypersensitivity reactions (e.g., pruritus, rash, urticaria), including some serious events (e.g., hypersensitivity vasculitis and hypersensitivity reactions requiring hospitalization) Injection site reactions. Overall safety comparable to placebo

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm455883.htm

ODOMZO (sonidegib  Novartis, East Hanover, NJ)

Smoothened (Smo) antagonist which inhibits the Hedgehog (Hh) signaling pathway.

 Indication: Locally advanced basal cell carcinoma (BCC) that has recurred following surgery or radiation therapy, or those who are not candidates for surgery or radiation therapy.

 Efficacy:

Single study, n=194.

Objective Response rate 58% with 3 complete responses and 35 partial responses. 18% patients experienced subsequent disease progression with 4 of these 7 patients having maintained a response of 6 months or longer. The remaining 82% have ongoing responses ranging from to 1.9+ to 18.6+ months

 Safety: Most serious- Musculoskeletal adverse reactions. Other common adverse reactions including muscle spasms, alopecia, dysgeusia, fatigue, nausea, decreased weight, decreased appetite, myalgia, pain, and vomiting

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm455862.htm

TECHNIVIE (AbbVie Inc. North Chicago, IL)

Fixed-dose combination tablet containing ombitasvir (hepatitis C virus NS5A inhibitor), paritaprevir (hepatitis C virus NS3/4A protease inhibitor), and ritonavir (CYP3A inhibitor, inhibits CYP3A mediated metabolism of paritaprevir and therefore increases its systemic exposure) for oral administration.

 Indication : TECHNIVIE is indicated in combination with ribavirin for the treatment of patients with genotype 4 chronic hepatitis C virus (HCV) infection without cirrhosis

Efficacy:

PEARL-1. N= 135, with chronic HCV genotype 4 infections without cirrhosis. Technivie with ribavirin vs Technivie without ribavirin. Sustained virologic responses after week 12: 100% for Technivie + ribavirin,  91 percent for technivie only.

 Safety

Increased Risk of ALT Elevations requiring hepatic laboratory testing. Other reactions were Fatigue, Nausea, Insomnia, Pruritus, Skin reactions

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm455857.htm

 medwatch

Brintellix (vortioxetine) and Brilinta (ticagrelor): Drug Safety Communication – Name Confusion

guidance_prop namesISSUE: Reports of confusion between the antidepressant BRINTELLIX and anti-coagulant BRILLINTA have resulted in the wrong medication being prescribed or dispensed.

RECOMMENDATION: Include generic (established) name i.e. vortioxetine or ticragrelor, in addition to the brand name

STORYLINE : FDA has established a fairly rigorous procedure for Proprietary Name assessment based on safety aspects to reduce medication errors, and promotional implications that has helped reduce medication errors. Learnings from this latest report will be important in updating review standards.

http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm456569.htm

Current status of Ebola Vaccine research

ebola

Experimental Ebola vaccine tested on thousands of people and might help shut down the waning epidemic in West Africa. Merck, Johnson & Johnson and GlaxoSmithKline already have their candidates in mid-stage trials. Novavax completed Phase I trial.

Merck

Merck stated that its investigational Ebola vaccine candidate, rVSV-ZEBOV, was found to have 100 percent efficacy based on an interim data analysis from a Phase 3 ring vaccination trial in Guinea. The authors report that vaccine efficacy was 100 percent (95% confidence interval: 74.7 – 100%; p=0.0036) following vaccination with a single dose of the rVSV-ZEBOV vaccine.

In late 2014, when the current Ebola outbreak was at its most severe, Merck was licensed rVSV-ZEBOV from NewLink Genetics Corporation. Vaccinated individuals developed antibodies against the Ebola virus, which would help protect against future infection. It appeared that all vaccinated individuals were protected against Ebola virus infection within 6 to 10 days of vaccination. To date, the rVSV-ZEBOV vaccine has been administered to more than 9,000 people in phase 1, 2 and 3 clinical trials. The significance and durability of this immune response have not been determined.

GSK and J&J/Bavarian Nordic

GlaxoSmithKline recently reported positive results from the Liberian Phase II trial of its candidate and that it may advance to Phase III. Johnson & Johnson announced in March that it was ready to start trialing its vaccine candidate in Ghana, Tanzania and Kenya.

Novavax

Novavax took its Ebola vaccine candidate to Australia for a Phase I trial. The company reported positive top-line results from the 230-person trial. The ebolavirus glycoprotein recombinant nanoparticle vaccine, or Ebola GP vaccine for short, was well-tolerated and provoked high ebolavirus antibody responses, said Dr. Greg Glenn, Novavax’s research chief, in a statement.

“We’re not at the same stage as some of the other developers … but what we have is an improvement over what’s already being tested,” Glenn said, as quoted by Reuters. If all goes well, the vaccine could be market-ready in two to three years, he said.

ebola_WHO

Health workers in Guinea check the blood pressure and other vital signs of a man about 30 minutes after he was given the trial Ebola vaccine. Photo by WHO