FDA News, Week of July 20, 2015

Improving Access to Medical Devices: FDA Uses Existing Clinical Data to Reduce Premarket Data Needs

Ben Fisher, Ph.D., Director, Division of Reproductive, Gastro-Renal, and Urological Devices, ODE, CDRH.

Utilizing publicly available clinical data to design less burdensome clinical design for new medical devices to reduce cost and time for device clinical development.  Criteria:

More Collaboration, Research Needed to Develop Cures,

Robert Califf, M.D., Deputy Commissioner for Medical Products and Tobacco.

Focus on targeted drug development so that drug discovery and development is in pace with unmet needs for many diseases.

Improve the efficiency and predictability of clinical drug development using advanced scientific tools such as:

  • genomic data, biomarkers and surrogate endpoints
  • modernized clinical trial designs, disease modeling and clinical trial simulation (bioinformatics)
  • advanced imaging technology

Focus on four key disease areas other than cancer and HIV/AIDS.

  • Alzheimers
  • Diabetes
  • Rare disease (<20,000 patients)
  • Hepatitis C


Storyline : CDER and CDRH recent blogs draw attention to FDA’s focus on innovation.  In keeping with the spirit of the 21st Century Cures Act, Senior CDER and CDRH members are highlighting approaches to drug/device development that could enable quicker access to new therapies and devices that have been demonstrated to be safe and effective.

FDA approved

Theranos secures FDA CLIA waiver for the Herpes simplex 1 virus Lab Test (Theranos, Palo Alto, CA)

theranosTest system for the herpes simplex 1 virus IgG (HSV-1), which was cleared by the FDA earlier this month, received a Clinical Laboratory Improvement Amendments (CLIA) Waiver from FDA, permitting its use in locations outside of traditional clinical laboratories. The decision is based on submission of comprehensive data, beyond the extend required by the FDA, to demonstrate the reliability and accuracy of test outside certified laboratories. Data demonstrated that conditions expected in non-laboratory testing would not affect the integrity of results – temperature fluctuations, humidity, tilting, power fluctuations, contamination, and storage and shipping conditions, among other variables in samples and conditions

Storyline : The approval of the kit and its subsequent CLIA waiver is in line with Theranos’ mission is to make actionable information accessible to everyone at the time it matters most. The company is also active in interacting with FDA on developing framework for regulation of Laboratory Developed tests (LDTs) https://www.theranos.com/content/pdf/theranos_comment_ldt_guidance.pdf

Edwards SAPIEN 3™ Transcatheter Heart Valve (Edwards Lifesciences LLC, Irvine, CA )


Regulatory Pathway : PMA, Priority Review ( availability of the device is in the best interest of the patients). No Advisory Committee Meeting.

Indications for Use : Relief of aortic stenosis in patients with symptomatic heart disease due to severe native calcific aortic stenosis who are judged by a heart team, including a cardiac surgeon, to be at high or greater risk for open surgical therapy


  • PARTNER II trial, single arm, non-randomized, historical-controlled study to compare the third generation Edwards SAPIEN 3 THV system with the first generation Edwards SAPIEN THV system in patients who either have high risk for surgery or cannot undergo surgery
  • Supplemental : Study S3OUS conducted in Europe and Canada to support the CE Mark.
  • Primary Endpoint : Composite of all cause death, stroke, and aortic insufficiency (AI) ≥ moderate at 30 days : 6.7% (SAPIEN 3) vs . 15.6% (SAPIEN) meeting pre-specified non-inferiority criteria in PARTNER II. Supported by ex-US study outcomes.
  • Supportive secondary endpoints were improvement in AI, Major Vascular Complications, improvement in valve performance, 6 min walk test, Length of Stay in ICU, NYHA classification, QoL measures

Safety : Procedure related complications such as death, stroke, myocardial infarction, major vascular complications, bleeding, conduction disturbance, and acute kidney injury.

Benefit/Risk : probable benefits (improved valve hemodynamic performance, functional status, QoL) outweigh procedure related risks in patients with severe native aortic stenosis who are at high or greater risk for open aortic valve replacement surgery.

activL® Artificial Disc (Aesculap Implant Systems, LLC, Center Valley, PA)

artificial disk

Intended Use: Reconstruction of the disc at one level (L4-L5 or L5-S1) following single-level discectomy in skeletally mature patients with symptomatic degenerative disc disease (DDD) with no more than Grade I spondylolisthesis at the involved level.

Reg pathway : PMA. No Advisory Committee.


  • Randomized (2:1), single masked, concurrently controlled, non-inferiority clinical trial to compare the safety and effectiveness of the activL to one of two alternative lumbar total disc replacement control devices (DePuy Spine Charité (Charité) or DePuy Synthes Spine ProDisc-L (ProDisc-L)).
  • Post-operative success (improvement in pain and disability) at 24 mo composed of Oswestry Disability Index (ODI), neurological status, radiographic range of motion status, device status, and no serious device related adverse events. Noninferiority demonstrated.

Safety: Adverse event rates, neurologic status, and the need for subsequent surgery at the index level similar to comparative devices.


Drug Approvals:

  • Praluent (alirocumab) injection : For use in addition to diet and maximally tolerated statin therapy in adult patients with heterozygous familial hypercholesterolemia (HeFH) or patients with clinical atherosclerotic cardiovascular disease such as heart attacks or strokes, who require additional lowering of LDL cholesterol.
  • Odomzo (sonidegib) :  To treat patients with locally advanced basal cell carcinoma that has recurred following surgery or radiation therapy, or who are not candidates for surgery or radiation therapy.
  • Technivie (ombitasvir, paritaprevir and ritonavir) : For use in combination with ribavirin for the treatment of hepatitis C virus (HCV) genotype 4 infections in patients without scarring and poor liver function (cirrhosis).

Reviews to be posted next week

ASCO 2015 Highlights

ASCO ASCO Annual Mtg

The 51st ASCO Annual Meeting took place in Chicago May 29 – June 2, brought together more than 30,000 oncology professionals from a broad range of specialties from around the world. This year’s Annual Meeting was focused on the theme of Innovation and Illumination, pointing to the potential for integrating cancer science and health information technology to achieve more rapid improvements in patient care. Along with new research,

ASCO President Peter Yu, MD stated at the meeting, “We are in an information age and there is a lot of data coming at us. We need to become smarter and more nimble about how we look at data and derive knowledge, and then that drives actual decision-making that improves patient outcomes.”

Prostate Cancer Foundation’s a few highlights for patients

Upfront Therapy with Docetaxel Prolongs Overall Survival in Men with Hormone-Naïve Metastatic Prostate Cancer Commencing Androgen Deprivation Therapy: First survival results from STAMPEDE: Dr. Nicholas James, University of Warwick and Queen Elizabeth Hospital Birmingham.

Dr. Nicholas James presented the first survival results released from the STAMPEDE clinical trial, which tested the outcome of adding various therapies to standard of care (SOC) consisting of androgen deprivation therapy (ADT) with or without radiotherapy (RT), in hormone-naïve patients either presenting with metastatic disease or relapsing after prostatectomy or RT. Results were presented from four randomized study arms: SOC (1184 patients), SOC + zoledronicacid (593 patients), SOC + docetaxel + prednisolone (592 patients), and SOC + zoledronicacid + docetaxel + prednisolone (593 patients). No benefits to failure free survival (FFS) or overall survival (OS) were observed with addition of zoledronicacid, a bisphosphonate that reduces bone fractures and pain from bone metastases. The addition of docetaxel + prednisolone to SOC extended median FFS from 21 months to 37 months and extended median OS from 67 months to 77 months. These results supported previous results from the CHAARTED trial where a median overall survival (OS) improvement from 44 to 57.6 months with the addition of docetaxel to ADT in hormone-sensitive metastatic prostate cancer patients was observed. Collectively, these results supported a paradigm change in clinical practice. Docetaxel in combination with ADT should now be considered much earlier in the treatment regimen for men with hormone-naïve metastatic prostate cancer.

Neoadjuvant Chemotherapy Combined with ADT and IMRT Shows Survival Benefit in Localized High-Risk Prostate Cancer Patients: Results from RTOG 0521. Dr. Howard Sandler, Cedars-Sinai Medical Center

Dr. Howard Sandler presented results from RTOG 0521, a Phase III trial testing the addition of docetaxel + prednisone to ADT+ Intensity-Modulated RT (IMRT) in treatment-naïve high-risk localized prostate cancer. At a median of 6 years of follow up, 563 patients were evaluable. The addition of docetaxel + prednisone to ADT + IMRT improved the 4-year overall survival (OS) rate from 89% to 93% of patients and improved 6-year disease-free survival rates from 55 to 65%. These studies indicated that neoadjuvant chemotherapy in combination with ADT and IMRT may benefit patients with localized high-risk prostate cancer and should be considered as the first line of therapy. These studies indicate that neoadjuvant chemotherapy in combination with ADT and IMRT may benefit patients with localized high-risk prostate cancer and should be considered as the first line of therapy.

Genomic Analysis of Circulating Cell-free DNA Identifies Mechanisms of Primary and Acquired Resistance to Enzalutamide in Metastatic Castration-Resistant Prostate Cancer (mCRPC). Dr. Arun Azad, BC Cancer Agency, Vancouver, Canada

Dr. Arun Azad (BC Cancer Agency, Vancouver, Canada) and colleagues assessed genomic alterations in cfDNAfrom metastatic castrate resistant prostate cancer (mCRPC) patients prior to and following the development of resistance to treatment with enzalutamide.Poorer median progression-free survival (mPFS) in response to enzalutamide was associated with pre-existing copy-number amplifications of the oncogenes AR, MYC and MET, mutations in AR, or copy-number losses of the tumor-suppressor gene RB1. Ten of 44 patients acquired new copy-number changes during enzalutamide treatment. Acquired AR or MYC amplifications or RB1-loss were associated with poorer mPFSduring treatment with enzalutamide. Five patients acquired new AR mutations during enzalutamide treatment and also had significantly reduced mPFS. Ongoing studies are assessing tumor genomic alterations in patients enrolled in clinical trials with other therapies. These studies will lead to the establishment of Precision Medicine treatment models, in which tumor genomic profiles are used to select treatments most likely to provide benefit and avoid treatments for which benefit is unlikely.

Statin Use at the Time of Initiation of Androgen Deprivation Therapy Delays Time to Progression in Patients with Hormone-Sensitive Prostate Cancer. Dr. Lauren Harshman, Dana-Farber Cancer Institute, Harvard Medical School.

Dr. Lauren Harshman and colleagues hypothesized that the use of statins may boost the efficacy of androgen deprivation therapy (ADT) by competing with DHEAS for SLCO2B1 uptake and thereby further limiting the amount of androgens available to fuel prostate cancer cells. In a retrospective analysis of 926 analyzable patients who initiated ADT between 1996 and 2013, statin use at the time of ADT initiation was associated with a significantly increased median time to progression on ADT (27.5 months for statin users vs. 17.4 months for non-statin users). These differences were observed regardless of whether patients had radiographic evidence of metastasis or only biochemical relapse at the time of ADT initiation. These results require validation in a prospective study and further studies are needed to definitively define the mechanisms involved. Nevertheless, statins have an established safety profile and may be an effective anti-cancer therapeutic in combination with ADT

Other Hightights

The Saturday, May 30, Education Session of “Introduction to Methods in Comparative Effectiveness Research,” chaired by Sharon H. Giordano, MD, MPH, of The University of Texas MD Anderson Cancer Center, provided an overview of a variety of approaches to comparative effectiveness research (CER).

“A lot more people are starting to conduct research in this area,” Dr. Giordano said. “There has been a general realization that, although it would be ideal to do a randomized clinical trial for every situation in every population, it is not realistic, and because of those gaps in knowledge, people are interested in using comparative effectiveness research to help determine the best way to treat their patients. The purpose of CER is to assist consumers, clinicians, purchasers, and policy makers to make informed decisions that will improve health care at both the individual and population levels.”

Natasha K. Stout, PhD, of Harvard Medical School and Harvard Pilgrim Health Care Institute, discussed the use of disease simulation modeling in CER. Disease simulation modeling is an Institute of Medicine -endorsed methodology that helps to fill evidence gaps left by clinical trials or observation studies. According to Dr. Stout, models can often be used in cases in which a decision needs to be made immediately but for which traditional research would take years to produce an outcome of interest. Modeling can project both near- and long-term outcomes in a timely manner, and, in some cases, can project the value of conducting more research in a given area.

PK poster presentation:

PK of the chimeric anti-GD2 (ch14.18) antibody in children with high-risk neuroblastoma: Children’s Hospital of Philadelphia, PA and United Therapeutic Corp,, RTP, NC

Ch14.18 is a Chimeric Monoclonal Antibody (cMoAb), improves survival in high-risk neuroblastoma according previously reported study. Ch14.18 disposition was highly variable in children. Infusion dose was of 25 mg/m2 over 10 h to male (n-6) and female (n=4) children of 1 to 7 yr old. Mean Cmax, half-life (HL) clearance (CL) and volume distribution (Vd) were 14 mcg/mL, 260 hr, 11 mL/h/m2 and 2.8 L/m2, respectively. C14.18 CL, Vd and HL in children were similar to those in adults at same dose level.


FDA News, Week of July 13th

century curesUS House passes 21st Century Cures Act to accelerate drug approvals

  • Removing barriers to increased research collaboration
  • Incorporating the patient perspective into the drug development and regulatory review
  • Measuring success and identifying diseases earlier through personalized medicine.
  • Modernizing clinical trials.
  • Removing regulatory uncertainty for the development of new medical apps
  • Providing new incentives for the development of drugs for rare diseases
  • Helping the entire biomedical ecosystem coordinate more efficiently to find faster cures

Storyline :  Step in the right direction for expedited development of drugs and devices (including Apps). However, use of non-traditional approaches for drug approval, e.g. biomarkers, Patient Reported Outcomes, will still need to meet evidentiary standards for the protection of public health. http://energycommerce.house.gov/cures

FDA approved

FDA Approval: In vitro Diagnostic test :VENTANA ALK (D5F3) CDx Assay (Ventana Medical Systems, Inc. Tucson, AZ)

Reg pathway : PMA

Indication : Qualitative detection of the anaplastic lymphoma kinase (ALK) protein in formalin-fixed, paraffin-embedded (FFPE) non-small cell lung carcinoma (NSCLC) tissue stained with a BenchMark XT automated staining instrument. It is indicated as an aid in identifying patients eligible for treatment with XALKORI® (crizotinib).

Clinical Program : Clinical outcome results and retrospective samples from Phase 3 Pfizer Study of efficacy and safety study of crizotinib vs. first-line chemotherapy (pemetrexed/cisplatin or pemetrexed/carboplatin) in previously untreated patients with ALK positive locally advanced or metastatic nonsquamous NSCLC.

Effectiveness : Based on agreement rates between the VENTANA ALK (D5F3) CDx Assay and the FDA-approved Vysis ALK Break Apart FISH Probe Kit. A statistically significant efficacy benefit for crizotinib vs. chemotherapy was observed in the subset of NSCLC patients whose tumors had ALK protein expression, as detected by the VENTANA ALK (D5F3) CDx Assay.

Safety : No additional safety hazard as tissues are routinely removed as part of NSCLC diagnosis.

Benefit/Risk : Adds another option of screening and diagnosis of ALK positivity as a key part of diagnostic evaluation for NSCLC patients supporting crizotinib treatment options.


FDA Approval : Atypical antipsychotic Rexulti (Brexpiprazole, Otsuka Pharmaceuticals, Tokyo Japan, Princeton, NJ)

Indication : Adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD), and Treatment of schizophrenia

Efficacy :

MDD :   Rexulti superior to placebo in change from baseline to Week 6 in the Montgomery-Asberg Depression Rating Scale (MADRS) in 2 studies.

Schizophrenia :  Rexulti superior to placebo in change from baseline to Week 6 in the Positive and Negative Syndrome Scale (PANSS) total score in 2 studies

Safety: Increased risk of death in patients with dementia-related psychosis, risk of suicidal thoughts and behaviors

Storyline : Brexpiprazole being positioned as a better alternative to aripiprazole that has lost patent exclusivity.


FDA Approval : Tyrosine kinase inhibitor, Iressa (Gefitinib, AstraZeneca, Wilmington, DE)

Reg Pathway :  Orphan Drug Designation, Concurrent labeling expansion of the therascreen EGFR RGQ PCR Kit, a companion diagnostic test for patient selection.

Indication : For the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test.

Efficacy : Single trial in metastatic NSCLC containing EGFR exon 19 deletions or L858R substitution mutations. Tumor samples tested retrospectively using the therascreen® EGFR RGQ PCR Kit . A 50% objective response rate with a median duration of response of 6 months. Response rates were similar in patients whose tumors had EGFR exon 19 deletions and exon 21 L858R substitution mutations.

Supportive exploratory anlaysis in patients with metastatic adenocarcinoma histology NSCLC receiving first-line treatment. Median Progression Free Survival of 10.9 months vs 7.4 months for the carboplatin/paclitaxel. Duration of Response 9.6 months vs 5.5 months.

Safety : Most common skin reactions, aspartate aminotransferase (AST) increased, alanine aminotransferase (ALT) increased, proteinuria, and diarrhea

Storyline : Iressa has received Accelerated Approval in 2003 for the broad indication of metastatic NSCLC, third line setting without demonstration of clinical benefit. Phase IV commitments under Subpart H, failed to demonstrate increase in survival, and the drug was withdrawn. This new approval is based on demonstration of clinical benefit in specific NSCLC patient subsets – for optimized, individualized therapy.http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm454692.htm

FDA News, Week of July 6th


Biomarker guidance

FDA Guidance on Biomarker Qualification

Drug Development Tool, from CDER’s Biomarker Qualification Program. Provides qualified context of use (COU) for the biomarker plasma 29 fibrinogen for COPD trials, experimental conditions and constraints, patient selection, and options for enrichment designs. CDER Biomarker Qualification program

Storyline : Framework for scientific development and regulatory acceptance of biomarkers for use in drug development

SBIA WebinarEndtoEnd

Storyline : FDA encouraging End-to-End capture to streamline and standardize data capture and enhance FDA review

Oncologic Drugs Advisory Committee :  Necitumumab for Squamous Non Small Cell Lung Cancer, (Eli Lilly, IN)  

 An FDA advisory panel indicated  that the benefits of Eli Lilly’s investigational lung cancer drug necitumumab outweigh its risks. Most panel members described the drug’s survival benefit as modest, yet meaningful, and in line with other FDA-approved therapies, but they suggested measures should be adopted to mitigate its potential risks particularly potentially fatal thromboembolic events.

Storyline : Impact of ODAC favorable assessment on FDA Action and Labeling awaited.

FDA approved

PromusPROMUS Element Plus Everolimus-Eluting Platinum Chromium Coronary Stent System (Monorail and Over-The-Wire), and Promus PREMIER Everolimus-Eluting Platinum Chromium Coronary Stent System (Monorail and Over-The-Wire) (Boston Scientific Corporation , MN)

Regulatory Pathway : PMA Supplement to support expansion of the indications to medically treated diabetes. Original PMA approved Nov  2011

Indication (expanded) : The PROMUS Element™ Plus and Promus PREMIER™ Everolimus-Eluting Platinum Chromium Coronary Stent Systems are indicated for improving luminal diameter in patients, including those with diabetes mellitus, with symptomatic heart disease or documented silent ischemia due to de novo lesions in native coronary arteries ≥2.25 mm to ≤4.00 mm in diameter in lesions ≤34 mm in length.

PLATINUM Clinical Program (PMA and Supplements) : Several studies  – small vessel,  long lesion,  pharmacokinetics, quantitative coronary angiography, US Post Approval Study – latter for this supplement)

Effectiveness , The 12-month Cardiac Death (CD)/Myocardial Infarction (MI) rate +  diabetic endpoint of target vessel failure (TVF) rate – both significantly lower than performance goal

Safety : Adverse event rates  clinically acceptable. Death, MI, and stent thrombosis low.

Benefit/Risk Assessment : The risks and benefits of the PROMUS Element Plus similar to other approved drug-eluting stents (eg TAXUS). Probable benefits outweigh the probable risks, and adds to the treatment options available to patients with symptomatic coronary artery disease

entresto moreENTRESTO 

Regulatory Pathway : Priority Review (approved prior to Action Date), Fast Track designation

Indication : ENTRESTO is combination of sacubitril, a neprilysin inhibitor, and valsartan, an angiotensin II receptor blocker, indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction.

Efficacy: Single pivotal study.  PARADIGM-HF demonstrated Entresto (sacubitril + RAS inhibitor valsartan) , superior to another RAS inhibitor (enalapril), in reducing the risk of the combined endpoint of cardiovascular death or hospitalization for heart failure, based on a time-to-event analysis (hazard ratio [HR]: 0.80,  p <0.0001). Also improved overall survival (HR 0.84; p = 0.0009)

 Safety: Angioedema higher with Entresto particularly in Black patients (2.4% vs 0.5%)

2015 BIO International Convention


The Department of Community and Economic Development welcomed the 2015 BIO International Convention, June 15-18 at Pennsylvania Convention Center, Philadelphia, hosted by the Biotechnology Industry Organization. More than 15,000 leaders from 69 countries and 49 states were participated.

Here are highlights:

Keynote Speaker Tom Brokaw (on June 16)

Brokaw described his observations on the state of the U.S. and the world with important political headlines, economic challenges and social issues in the news—and the people behind the headlines. He mentioned about the challenges that face America in the new millennium and offered reflections on how we can restore America’s greatness. In 2014, President Obama awarded Brokaw with the Presidential Medal of Freedom.

He talked to Dr. Oz, in an interview, about beating multiple myeloma with a nagging back pain. Multiple myeloma is a cancer formed by malignant plasma cells. Brokaw said “what happens is that the white blood cells invade the bone marrow.” His cancer is now in remission, although he is still dealing with some bone damage that comes with this type of cancer. As a result he had some unexpected fractures in his back and in pelvic area but they’re beginning to heal.

Keynote Speaker Dr Eric Topol (on June 17)

Dr. Eric Topol mentioned the importance of the Precision Medicine Initiative as a way to further revolutionize how we improve health and treat disease with early diagnostic and personalized treatment.

He mentioned, in partnership with the Wireless-Life Sciences Alliance, the Digital Health program would explore the intersection of digital health, biotech and pharma. Industry thought leaders, stakeholders and innovators would highlight digital health’s role in drug development, clinical trials, medication compliance, prescribable apps, new business models, big data and much more.


Start-ups get chance to shine at BIO convention

This year’s event attracted close to 16,000 industry leaders to Philadelphia, as well as Mayor Nutter, Gov. Wolf, and other government and civic leaders. Mayor said, “As home to an extraordinary lineup of education, health, and biotech-related organizations, our region set the tone for the high-energy buzz.”

One of the most exciting events of BIO was the Start-Up Stadium, which gave seed-stage companies the opportunity to pitch to potential investors, venture philanthropy groups, and other attendees from across the country and around the world. In the style of the popular Shark Tank TV show, the judges provided live feedback and interacted directly with the 30 start-up business owners, almost all of whom were based in Pennsylvania, New Jersey, or Delaware.

The innovative products that were showcased ranged from digital-health solutions to new methods of DNA testing and unique therapy delivery options.

The founder of Biomeme conducted a live demonstration of a testing device that enables health and government authorities to treat the sick and protect the healthy by using a hand-held device that lets them isolate and detect DNA and RNA in under an hour.

Another innovation on display was DenovoNow, a mobile platform that increases patient engagement by enhancing and further personalizing a patient’s relationship with his or her doctor at no additional cost to either party.

The other cutting-edge pharmaceutical and therapeutic treatments presented included a product developed by InteguRx Therapeutics described about one of their product that delivers once-daily anti-nausea treatment in a very small dose via a gel or patch to treat pregnancy-induced nausea and vomiting.

With the large pharmaceutical companies and biotech firms starting to look more to external sources for the next wave of innovation, the sessions were very well-attended. The investor community remains key to the success of these companies, and the Start-Up Stadium attracted investor judges from groups such as the Bill & Melinda Gates Foundation, New Enterprise Associates, Bristol-Myers Squibb, Flagship Vetnures, J&J Innovation Center, and Roth Capital Partners.

 Complexities of Rare Diseases Take the Spotlight at BIO

Nicole Boice, Global Genes Founder, addressed the BIO 2015 Orphan & Rare Disease Track by saying: “We’re all working to eliminate the challenges of rare diseases, but patients and their advocates aren’t always equipped to fight.” Organizations like Global Genes helped families affected by rare disease by connecting them with much needed tools and resources.

He said, “Understanding the distinctions is an important part of understanding the state of the orphan drug development worldwide, both where it’s going and where it needs to go. However, the various stakeholders involved in the development and administration of orphan drugs tend to define rare diseases differently. Regulators define rare diseases by the number of patients affected, FDA defines a rare disease as affecting less than 200,000 Americans per year.. Most importantly, for patients the concept of “rare” can manifest itself as isolation from others, which is a problem that industry should address as it also seeks to develop innovative orphan drugs. However, when taken together, rare diseases as a whole affect a large number of patients worldwide.”

 Can Vaccination, Diagnostics Help to Combat Antibiotic Resistance?

Resistance to antibiotics and other antimicrobials is growing worldwide, with deaths from resistant infections at about 700,000 per year, and estimated to rise to 10 million per year by 2050.

“The problem is so serious that it threatens the achievements of modern medicine,” the World Health Organization (WHO) wrote in a recent report. In late May, the WHO formally endorsed an international plan, which calls for all member states to have national plans in place by May 2017 to stop the growth of resistant germs globally. A major component of the plan is to develop novel antibiotics, but strengthening surveillance of these drugs is of utmost importance.

“Vaccines are not the solution, obviously, but this is an ‘all hands on deck’ problem,” said Bruce Gellin, deputy assistant secretary for health and director of the National Vaccine Program Office at the BIO International Convention 2015 in Philadelphia. “And vaccines need to be a part of the discussion.”

Targeting pathogens with antibiotic-resistant strains

 In 2005, a vaccine for Staph infection by Nabi Biopharmaceuticals failed to reduce infections among kidney patients in late-stage trials. Staph infections, caused by staphylococcus bacteria, can turn life-threatening if bacteria invade the bloodstream, joints, bones, lungs or heart. Treatment usually involves antibiotics and drainage of the infected area; however, some staph infections no longer respond to common antibiotics.

“It set the field back,” said Charles Knirsch, MD, MPH, vice president, therapeutic vaccines program lead, Vaccine Clinical Research and Development at Pfizer, referring to the failure of the single-antigen vaccine called StaphVax.

Currently, Pfizer is helping to usher in a new era of vaccine innovation — both to prevent and treat disease. Specifically, the company is working on a vaccine for methicillin-resistant Staphylococcus aureus (MRSA), the leading cause of hospital-acquired infections. MRSA infects an estimated 53 million people globally, and in the U.S. alone, MRSA kills 20,000 people each year. But rather than focus on a single target, Pfizer’s new approach, said Knirsch, contains four vaccine components to generate a broad immune response. “Sometimes, it’s more art than science getting those conjugates right, and we’ve been able to do it so far with these widely sharing antigens,” said Knirsch. “Because of the recurrent nature of this disease, we believe the vaccine would work like the pneumococcal vaccine, and reduce overall use of antibiotics.” Pfizer recently began enrollment in a Phase 2b clinical trial evaluating its investigational Staphylococcus aureus multi-antigen vaccine in adult patients undergoing spinal fusion surgery. Competitors, including GlaxoSmithKline, Novartis and Sanofi are also investigating Staphylococcus aureus vaccines.

Role and complexity of infectious disease diagnostics development

Inappropriate use, a reason for the rise in antibiotic resistance, includes starting patients on antibiotics before test results come back, putting them on a broad-spectrum antibiotics when it’s unknown what bacteria is causing an infection, or keeping them on medications even when tests come back negative.

“As a diagnostics company, how do we approach this paradigm?” asked Tom Lowery, Ph.D., chief scientific officer at T2 Biosystems in Lexington, Mass. Currently, a blood culture can take two to six days to process and what’s more, a blood culture often misses 50 percent to 60 percent of bloodstream and tissue-based infections, said Lowery. “Today, with the diagnostic paradigm, there’s a lot of guesswork, and with the significant delay, patients get put on broad-spectrum antibiotics unnecessarily.”

A solution? “Highly-sensitive, rapid tests that can give not only species identification but resistance identification within the first three to five hours,” said Lowery.

In that vein, T2 Biosystems’s FDA-approved diagnostic is the first sepsis pathogen diagnostic panel requiring no blood culture that identifies with 91.1 percent sensitivity the five clinically relevant species of Candida “directly from whole blood which enables physicians to initiate appropriate therapy on day zero,” according to the T2 Biosystems website. Candida is the most common cause of fungal infections worldwide.

Said Lowery, “This represents a new class of diagnostic test that can have the same, or better sensitivity, as blood cultures and deliver those results rapidly so that a clinician can put a patient directly on the targeted therapy that he should be on right away, without this waiting time, without this inappropriate therapy that can drive mortality rate up.”


Storyline: The 2015 BIO spanned a range of topics from classics such as rare disease complexities, antibiotics resistance to the innovatives such as Digital Health Solutions and Start-Up stadium. This was topped by having Tom Brokaw and Eric Topol  as the keynote speakers.

FDA Advisory Committee Meetings, July 2015

Public Meeting: Exploring Naloxone Uptake and Use (July 1-2)

FDA in collaboration with the National Institutes of Drug Abuse, the Centers for Disease Control and Prevention, the Substance Abuse and Mental Health Services Administration, and the Health Resources and Services Administration, is announcing a scientific workshop to initiate a public discussion about issues surrounding the uptake of naloxone in certain medical settings – such as on ambulances and in association with prescriptions for opioids – as well as outside of conventional medical settings to reduce the incidence of opioid overdose fatalities. Academia, government, industry experts, and patient advocates will discuss which populations are at risk for opioid overdose and how public health groups can work together to use naloxone to reduce the risk of overdose. We will also explore legal, regulatory, logistical and clinical aspects related to making naloxone more widely available. http://www.fda.gov/Drugs/NewsEvents/ucm442236.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery

Joint Meeting of the Drug Safety and Risk Management Advisory Committee and the Anesthetic and Analgesic Drug Products Advisory Committee (Jul 7-8)

The committees will discuss the results of post marketing studies evaluating the misuse and/or abuse of reformulated Oxycontin (oxycodone hydrochloride) extended-release tablets, supplemental new drug application (sNDA) 022272, manufactured by Purdue Pharma L.P. The committees will discuss whether these studies have demonstrated that the reformulated Oxycontin product has had a meaningful impact on abuse of Oxycontin. http://www.fda.gov/AdvisoryCommittees/Calendar/ucm448718.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery

Oncologic Drugs Advisory Committee (Jul 9)

The committee will discuss biologics license application 125547, necitumumab injection, application submitted by Eli Lilly and Company. The proposed indication (use) for this product is in combination with gemcitabine and cisplatin for first-line treatment of patients with locally advanced or metastatic squamous non-small cell lung cancer. http://www.fda.gov/AdvisoryCommittees/Calendar/ucm448239.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery

Public Meeting: Medical Device User Fee Reauthorization (Jul 13)

FDA will hold a public meeting to gather initial input on reauthorization of the Medical Device User Fee program, as required by section 738A of the Federal Food, Drug, and Cosmetic Act. Additional information and Federal Register announcement available.  http://www.fda.gov/MedicalDevices/NewsEvents/WorkshopsConferences/ucm445541.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery

Public Meeting: Prescription Drug User Fee Reauthorization (Jul 15)

The Federal Food, Drug, and Cosmetic Act (FD&C Act) requires that FDA hold public meetings and conduct discussions with both the regulated industry and stakeholder groups in developing recommendations for the next PDUFA program (FY2018-2022).https://s3.amazonaws.com/public-inspection.federalregister.gov/2015-11537.pdf?source=govdelivery&utm_medium=email&utm_source=govdelivery

Public Workshop: Robotically-Assisted Surgical Devices – Challenges and Opportunities (Jul 27-28)

The purpose of this workshop is to obtain public feedback on scientific, clinical and regulatory considerations associated with RAS devices. Comments and suggestions generated through this workshop will facilitate further development of regulatory science for RAS technologies. The participants of this workshop will discuss current challenges and opportunities related to RAS devices and address clinical, technical and training questions related to the safe and effective use of these devices. http://www.fda.gov/MedicalDevices/NewsEvents/WorkshopsConferences/ucm435255.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery

FDA News, July 5, 2015

FDA approved

proteusProteus Digital Health (redwood City, CA) has received an update to its FDA 510(k) clearance for its digital medicine platform, adding a new indication to the clearance. The system is now, to the company’s knowledge, the first technology to have an indication in its FDA clearance for measuring medication adherence. Reviews to be provided shortly

Storyline: This new digital. medicine technology could potentially address patient compliance issues and help ensure correct dosing.

Orkambi (Vertex Pharmaceuticals, Boston, MA)

First drug approved for cystic fibrosis directed at treating the cause of the disease in people who have two copies F508del mutation, which causes the production of an abnormal protein that disrupts how water and chloride are transported in the body

Orkambi (lumacaftor 200 mg/ivacaftor 125 mg) is now approved to treat cystic fibrosis (CF) in patients 12 years and older.

Expedited Development and FDA Review : Breakthrough Therapy designation, Priority Review, Orphan Drug Designation. Review to be posted shortly

Storyline:  Expedited review and approval underscores FDA’s commitment to innovative treatments for serious rare diseases