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COMBATING THE SILENT EPIDEMIC of VIRAL HEPATITIS
Action Plan for the Prevention, Care & Treatment of Viral Hepatitis
U.S. Department of Health & Human Services
INTRODUCTION
Viral hepatitis is a silent epidemic in the United States. Although it is a leading infectious cause of
death and claims the lives of 12,000–15,000 Americans each year, viral hepatitis remains virtually
unknown to the general public, at-risk populations, and policymakers (1–3); even health-care
providers lack knowledge and awareness about these infections (1). As a consequence, most of
the 3.5–5.3 million Americans living with viral hepatitis do not know that they are infected, placing
them at greater risk for severe, even fatal, complications from the disease and increasing the
likelihood that they will spread the virus to others. Viral hepatitis is a major cause of liver cirrhosis
and liver cancer in the United States (1–4); persons living with viral hepatitis are at increased risk
for both conditions.
In January 2010, the Institute of Medicine (IOM) released the report Hepatitis and Liver Cancer: a
National Strategy for Prevention and Control of Hepatitis B and C (1). In this report, IOM identifies
viral hepatitis as an underappreciated health concern for the nation and outlines multiple barriers
impeding efforts to prevent viral hepatitis transmission and disease. In its 2010 report, IOM
provides 22 specific recommendations to help improve 1) disease surveillance, 2) knowledge
and awareness of viral hepatitis among the public and providers, 3) access to vaccination, and 4)
delivery of viral hepatitis prevention and care services (Appendix A).
In response to the IOM report, Assistant Secretary for Health Dr. Howard Koh convened a Viral
Hepatitis Interagency Working Group comprised of subject matter experts from various U.S.
Department of Health and Human Services (HHS) agencies (Appendix B). This group was charged
with responding to the IOM comments by developing a comprehensive strategic viral hepatitis
action plan that would:
• address IOM recommendations for viral hepatitis prevention, care, and treatment;
• set forth actions to improve viral hepatitis prevention and ensure that infected persons are
identified and provided care and treatment; and
• improve coordination of all viral-hepatitis–related activities across HHS and promote
collaborations with other government agencies and non-governmental organizations.
To prepare the report Combating the Silent Epidemic of Viral Hepatitis: U.S. Department of Health
and Human Services Action Plan for the Prevention, Care and Treatment of Viral Hepatitis (referred
to as the Viral Hepatitis Action Plan), the Working Group convened expert panels from various
HHS agencies and offices (Appendix B). Panel members were tasked with developing components
of the action plan specific to their area of expertise. To engage key federal stakeholders in the
planning process, the Working Group solicited input from other government agencies. Additionally,
two meetings were held to solicit feedback from professional societies, community-based
organizations, and other members of the public.
VIRAL HEPATITIS: THE SILENT EPIDEMIC
An estimated 3.5–5.3 million persons are living with viral hepatitis in the United States, and
millions more are at risk for infection. Because viral hepatitis can persist for decades without
symptoms, 65%–75% of infected Americans remain unaware of their infection status and are not
receiving care and treatment (1). Most morbidity and mortality result from the chronic form of
viral hepatitis caused by hepatitis B virus (HBV) and hepatitis C virus (HCV) infection.
Viral hepatitis is the leading cause of liver transplantation in the United States (5). In the absence
of treatment, 15%–40% of persons living with viral hepatitis will develop liver cirrhosis (6–8) or
experience other conditions that affect the liver, including liver cancer. Rates of liver cancer have
tripled over the last several decades (4), with at least half of these cases attributable to HCV (9).
In the decade to come, more than 150,000 Americans are expected to die from viral-hepatitisassociated
liver cancer or end-stage liver disease (1).
Liver cancer and other liver diseases caused by viral hepatitis (e.g., cirrhosis) affect some U.S.
populations more than others, resulting in substantial health disparities. Persons with certain risk
behaviors, including men who have sex with men (MSM) and injection-drug users (IDUs), have
high rates of viral hepatitis. Also at risk are baby boomers. Compared with other age groups, a
greater proportion (about 1 in 33) of persons aged 46–64 years is infected with HCV (10). African
Americans are twice as likely to be infected with HCV when compared with the general U.S.
population (10), and approximately 1 in 12 Asian/Pacific Islanders (APIs) are living with hepatitis B,
representing half of all HBV-infected persons in the United States (11). These health disparities are
reflected in viral-hepatitis–associated morbidity and mortality; for example, liver cancer incidence
is highest among APIs and is increasing among African Americans, persons aged 46–64 years, and
men.
Persons with HIV also are disproportionately affected by viral hepatitis and related adverse health
conditions. Because HIV, HBV, and HCV share common modes of transmission, one third of HIV infected persons are coinfected with HBV or HCV. The progression of viral hepatitis is accelerated
among persons with HIV; therefore, persons who are coinfected experience greater liver-related
health problems than non-HIV infected persons (1–3,5,7,12).
Recipients of organs, blood, and tissue, along with persons working or receiving care in health
settings continue to be at risk for viral hepatitis infection. Although dramatic progress has been
made towards reducing the risk for health-care-associated HBV and HCV infections among these
persons, outbreaks continue to occur as a result of breakdowns in basic infection control and
limitations in the laboratory screening of donated organs, blood, and tissues.
In addition to causing substantial morbidity and mortality, viral hepatitis infection has adverse
economic consequences. End-stage treatments for viral hepatitis (e.g., liver transplants) are
expensive — the lifetime health-care costs for a person with viral hepatitis can easily total
hundreds of thousands of dollars (1). During the 1990s and early 2000s, hospital discharges with
an HBV diagnosis increased fourfold, with a rise in health-care costs from $357 million in 1990
to $1.3 billion in 2006 (13). Compared with other patients of similar age and sex, managed-care
enrollees with HCV are hospitalized more frequently (24% for HCV-infected persons versus 7%
for other patients) and have higher annual health-care expenses (approximately $21,000 per
HCV-infected enrollee versus about $5,500 for each non-infected enrollees), exceeding the
:person costs associated with diabetes (approximately $10,000 per year) (14–16). Hepatitis C also
increases other societal costs. A study of 339,456 workers revealed that employees with HCV had
significantly more lost work days than other employees, resulting in lost productivity (17).
Computer models indicate that cases of life-threatening liver disease caused by viral hepatitis
infections and health-care-associated costs will increase as infected persons grow older and as
their disease progresses (1,2). Fortunately, treatments for hepatitis B and hepatitis C can reduce
morbidity and are cost-effective (18,19). Economic studies of therapy have yielded estimates of
cost-saving to $33,900 per quality-adjusted life year (QALY) gained for HBV therapy and cost saving
to $120,000 per QALY gained for HCV therapy (20–34).
Current rates of viral hepatitis in the United States are reflective of the large global disease burden
involving hundreds of millions of persons. One in every 12 persons worldwide is living with viral
hepatitis; approximately 350–370 million persons are infected with HBV, and another 130–170
million are living with HCV infection (35–37). Globally, an estimated 78% of primary liver cancer
and 57% of liver cirrhosis cases are caused by viral hepatitis (36), and 1 million deaths from viral
hepatitis occur each year (35,36). The proportion of persons living with viral hepatitis is greatest
in Asia, sub-Saharan Africa, and Egypt; however, prevalence of HCV infection is high among
subpopulations (e.g., IDUs and persons living in correctional settings) in almost all parts of the
world. Increasing immigration to the United States from endemic countries has resulted in more
infections within U.S. borders; approximately 54,000 persons infected with hepatitis B immigrate
to the United States annually (CDC, unpublished data).
Calcsmart,
I have heard of the different govt. grants/projects only from JJ's press releases. I looked up some of the info. online from those agencies and got the feel that the HP because of its unique broad spectrum capabilities would be recognized by the govt.
From what I understand one would know of the status of the grants only when the approvals are announced.
Competitors - To my knowledge no one has the broad spectrum capacity which AEMD offers.
-CTSO - recently got approved by the EU for sepsis application
-Vrad - (Asahi Kasei Kuraray Medical Co., Ltd.) - this mainly deals with HCV
-Spectrum - again mainly for sepsis.
-Gambro - for toxins and sepsis?
AEMD is going to be participating here. Biotech companies dealing with Mab seem to be here also. I think JJ is going to be mainly presenting the ADAPT here.
http://www.techvision.com/c21/overview/
Better explanations of Monoclonal antibodies -
http://www.bio.davidson.edu/Courses/molbio/MolStudents/01rakarnik/mab.html
http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/M/Monoclonals.html
http://www.cancer.org/treatment/treatmentsandsideeffects/treatmenttypes/immunotherapy/immunotherapy-monoclonal-antibodies
This monoclonal antibody was developed jointly by FRESENIUS!!! - http://en.wikipedia.org/wiki/Catumaxomab
Monoclonal antibody therapy (Scroll to the info highlighted in bold - very smart move by JJ in naming it ADAPT - todays PR is making a lot of sense now!)
From Wikipedia, the free encyclopedia
Monoclonal antibodies (mAb or moAb) are monospecific antibodies that are the same because they are made by identical immune cells that are all clones of a unique parent cell.
Given almost any substance, it is possible to produce monoclonal antibodies that specifically bind to that substance; they can then serve to detect or purify that substance. This has become an important tool in biochemistry, molecular biology and medicine. When used as medications, the non-proprietary drug name ends in -mab (see "Nomenclature of monoclonal antibodies").
Each antibody binds only one specific antigen.
Monoclonal antibody therapy is the use of monoclonal antibodies (or mAb) to specifically bind to target cells. This may then stimulate the patient's immune system to attack those cells. It is possible to create a mAb specific to almost any extracellular/ cell surface target, and thus there is a large amount of research and development currently being undergone to create monoclonals for numerous serious diseases (such as rheumatoid arthritis, multiple sclerosis and different types of cancers). There are a number of ways that mAbs can be used for therapy. For example: mAb therapy can be used to destroy malignant tumor cells and prevent tumor growth by blocking specific cell receptors. Variations also exist within this treatment, e.g. radioimmunotherapy, where a radioactive dose localizes on target cell line, delivering lethal chemical doses to the target.[1]
Targeted conditions
[edit]Cancer
Anti-cancer monoclonal antibodies can be targeted against malignant cells by several mechanisms:
-Radioimmunotherapy (RIT) involves the use of radioactively conjugated murine antibodies against cellular antigens. Most research currently involved their application to lymphomas, as these are highly radio-sensitive malignancies. To limit radiation exposure, murine antibodies were especially chosen, as their high immunogenicity promotes rapid clearance from the body. Tositumomab is an exemplar used for non-Hodgkins lymphoma.
-Antibody-directed enzyme prodrug therapy (ADEPT) involves the application of cancer associated monoclonal antibodies which are linked to a drug-activating enzyme. Subsequent systemic administration of a non-toxic agent results in its conversion to a toxic drug, and resulting in a cytotoxic effect which can be targeted at malignant cells. The clinical success of ADEPT treatments has been limited to date.[15] However it holds great promise, and recent reports suggest that it will have a role in future oncological treatment.
-Immunoliposomes are antibody-conjugated liposomes. Liposomes can carry drugs or therapeutic nucleotides and when conjugated with monoclonal antibodies, may be directed against malignant cells. Although this technique is still in its infancy, significant advances have been made. Immunoliposomes have been successfully used in vivo to achieve targeted delivery of tumour-suppressing genes into tumours, using an antibody fragment against the human transferrin receptor. Tissue-specific gene delivery using immunoliposomes has also been achieved in brain, and breast cancer tissue.[16]
[edit]Autoimmune diseases
Monoclonal antibodies used for autoimmune diseases include infliximab and adalimumab, which are effective in rheumatoid arthritis, Crohn's disease and ulcerative Colitis by their ability to bind to and inhibit TNF-a.[17] Basiliximab and daclizumab inhibit IL-2 on activated T cells and thereby help preventing acute rejection of kidney transplants.[17] Omalizumab inhibits human immunoglobulin E (IgE) and is useful in moderate-to-severe allergic asthma.
The first FDA-approved therapeutic monoclonal antibody was a murine IgG2a CD3 specific transplant rejection drug, OKT3 (also called muromonab), in 1986. This drug found use in solid organ transplant recipients who became steroid resistant.[18] Hundreds of therapies are undergoing clinical trials. Most are concerned with immunological and oncological targets.
Since 2000, the therapeutic market for monoclonal antibodies has grown exponentially. The current “big 5” therapeutic antibodies on the market are bevacizumab, trastuzumab (both oncology), adalimumab, infliximab (both autoimmune and inflammatory disorders, ‘AIID’) and rituximab (oncology and AIID) accounted for 80% of revenues in 2006. In 2007, eight of the 20 best-selling biotechnology drugs in the U.S. are therapeutic monoclonal antibodies.[22] This rapid growth in demand for monoclonal antibody production has been well accommodated by the industrialization of mAb manufacturing.[23]
Exosomes research is showing a lot of results and gaining momentum -
http://janlotvall.wordpress.com/2011/05/17/thoughts-on-how-to-bring-the-exosome-and-microvisicles-communities-together/
Anyone have any idea of this? -
http://www.bharatbook.com/detail.asp?id=187025&rt=Aethlon-Medical-Inc-AEMD-Product-Pipeline-Analysis.html
Some interesting data from Australia - HIV/HCV coinfection patients may end up being prime targets for the HP! They are difficult to treat, have lot of comorbidities which make them prone to drug related side effects, etc.,
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6W7C-519DF0J-4&_user=10&_coverDate=05%2F31%2F2011&_rdoc=16&_fmt=high&_orig=browse&_origin=browse&_zone=rslt_list_item&_srch=doc-info(%23toc%236623%232011%23999459994%233107738%23FLA%23display%23Volume)&_cdi=6623&_sort=d&_docanchor=&_ct=43&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=d793b6fa68d1fd6eb5e9b99b467a36b9&searchtype=a
Results
The study cohort comprised 42,480 individuals with HBV mono-infection and 82,034 with HCV mono-infection. HIV co-infection increased the overall mortality rate three to 10-fold compared to mono-infected groups. Liver-related deaths were associated with high excess risk of mortality in both HBV and HCV groups (SMR 10.0, 95% CI 9.0–11.1; 15.8, 95% CI 14.8–16.8). Drug-related deaths among the HCV group also represented an elevated excess risk (SMR 15.4, 95% CI 14.5–16.3). Rates of hepatocellular carcinoma (HCC)-related death remained steady in both groups. A decrease in non-HCC liver-related deaths was seen in the HBV group between 1997 and 2006, but not in the HCV group. After a sharp decrease between 1999 and 2002, drug-related mortality rates in the HCV group have been stable.
Patients with TB and HCV together may benefit from the HP before starting antiTB meds -
http://www.journalofinfection.com/article/PIIS0163445311001149/abstract?rss=yes
RFA for better diagnostics - would the HP by virtue of removing the viruses would also be able to diagnose some of the viral pathogens mentioned below?
http://grants.nih.gov/grants/guide/rfa-files/RFA-AI-11-024.html
Responsive projects will focus on development of improved and/or field-appropriate diagnostics for at least one of the following pathogens:
Bacteria
Salmonella enterica
Vibrio cholerae
Escherichia coli (diarrheal)
Shigella spp.
Campylobacter jejuni
Borrelia burgdorferi
Viruses
Ebola Virus (EBOV)
Marburg Virus (MARV)
Lassa Virus (LV)
Dengue Virus (DENV)
Chikungunya Virus (CHIKV)
Japanese Encephalitis Virus (JEV)
Eastern Equine Encephalitis Virus (EEEV)
West Nile Virus (WNV)
Enterovirus 71 (EV71)
Diarrheagenic enteric viruses
Is there scope for the HP here?
http://grants.nih.gov/grants/guide/rfa-files/RFA-AI-11-014.html
Therapeutics for Biodefense
Development of safe and effective antimicrobials against biodefense agents and emerging pathogens is a high priority. Applications for preclinical development of a therapeutic that targets a NIAID Category A, B, or C priority agent are invited, with particular interest in therapeutics targeting antibiotic-resistant pathogens and/or pathogens for which no standard clinical treatment exists.
The NIAID Strategic Plan for Biodefense Research emphasizes development of broad spectrum therapeutics. An anti-infective characterized by broad spectrum activity might target a common, invariable, or essential component of different classes of microbes and potentially be effective against traditional and non-traditional agents. Applications for development of either a broad spectrum anti-infective against multiple NIAID Category A, B, or C agents, or a broad spectrum anti-infective against a non-listed agent that would also protect against a listed NIAID Category A, B, or C agent, are encouraged. Applications proposing development of a therapeutic against a non-listed antibiotic-resistant pathogen must focus on development of a broad-spectrum therapeutic. For these projects, applicants must clearly describe the broad-spectrum capability of the proposed therapeutic technology.
Therapeutics projects may include, but are not limited to, one or more of the following product development activities:
Lead optimization:
Synthesizing, purifying, and testing drugs/inhibitors for efficacy and toxicity in model assays and preclinical in vivo systems;
Performing preliminary pharmacokinetic and pharmacodynamic analyses on lead compounds;
Preclinical testing for safety in animals;
Optimization of dose, dosing interval, and route of delivery in preclinical evaluation or in animal models;
Determination of drug interactions in host molecular processes;
Methods to modify existing antimicrobials to improve half-life in vivo, microbial clearance rates, or tissue accessibility; or to decrease adverse side effects of administration;
Evaluation of the potential for the emergence of drug resistance in model systems;
Assessing bioavailability and mechanism of action;
Process development for the manufacturing of drugs, including QA/QC, methods for product recovery, characterization, purification, identity, stability etc.; and
Performing required benchmarks for successful submission and review of an IND application by the FDA (www.fda.gov/cder/regulatory/default.htm).
This is interesting - there seems to be 2 parts to this BAA - vaccine component and a technology component to enhance the effect of the vaccine. The HP certainly is effective against a lot of the mentioned pathogens. I have copied some of the info relevant to the HP.
https://www.fbo.gov/index?s=opportunity&mode=form&id=aa22c918e89875f56b8182a3ad1ac203&tab=core&_cview=1
Description
The primary objective of this solicitation is to support the advanced development of candidate products which consist of a vaccine component and a technology that accelerates the immune response for use in post-event settings following the intentional release of NIAID Category A and B Priority Pathogens excluding B. anthracis or in response to naturally occurring outbreaks of infectious diseases caused by NIAID Category A and B Priority Pathogens excluding B. anthracis. In these settings, simplicity and efficiency of delivery of vaccine to, and the effectiveness in large numbers of patients are key considerations.
Candidate products that increase vaccine stability and/or reduce logistical requirements are important secondary objectives and would further enhance the capabilities of a candidate product that accelerates the immune response. Anticipated benefits may include: decreased manpower and time required to prepare and administer the vaccine, maximum compliance of the vaccine recipients, and production of a protective immune response with 1-2 doses of vaccine.
Organizations responding to this Broad Agency Announcment should have documented expertise in product development, including regulatory submissions, to advance the development and evaluation of candidate products, against biological threats identified as NIAID Category A and B Priority Pathogens (http://www.niaid.nih.gov/topics/BiodefenseRelated/Biodefense/research/pages/cata.aspx) or Top Priority Biological Threats in the HHS, 2007 PHEMCE Implementation Plan (https://www.medicalcountermeasures.gov/BARDA/PHEMCE/enterprise/strategy/strategy.aspx).
Eligible candidate products include those for agents identified as NIAID Category A and B Priority Pathogens excluding B. anthracis.
2.Technology Component
a.The technology components used in the proposed candidate product may consist of a new adjuvant, an immune modulator, a formulation technology or a delivery platform designed to enhance the immune response onset for category A excluding B. anthracis and Category B priority pathogen vaccine candidates. Simply changing a vaccine formulation, for example taking a liquid to a stable lyophilized vaccine formulation, would not be sufficient to meet the objectives.
b.Technology components should address reduced time to establish immunity with proof of concept efficacy data in animal models that demonstrate efficacy with the proposed vaccine- component and the feasibility of attaining a safety profile that meets all existing U.S. Food and Drug Administration (FDA) requirements.
It is anticipated that multiple cost reimbursement, completion type contracts will be awarded for a 5 year period of performance beginning on or about April 1, 2012.
The NIAID estimates that one or more contracts may be issued for a total cost (direct and indirect costs combined) of up $44.5 million for a five-year period of performance. Importantly, contract activities will be divided into manageable time frames with initial funding of only the Base Period. Funding of subsequent timeframes will be funded by Options. Each Option will be fully funded when exercised and will be dependent on successful completion of critical predecessor activities, including USG acceptance of associated deliverables when applicable. The critical predecessor activities should constitute Go/No Go criteria for successor activities. The contract budget will be aligned with the Base Period, Options and associated tasks identified in the Product Development Plan and associated Gantt Chart.
HCV and HIV coinfection - technical, relevant info is highlighted. This can be a big market for the HP just like ESRD.
Treatment of hepatitis C virus (HCV) infection in patients coinfected with HIV in the HIV Outpatient Study (HOPS), 1999-2007
Authors: Vellozzi, C.1; Buchacz, K.1; Baker, R.2; Spradling, P. R.3; Richardson, J.2; Moorman, A.3; Tedaldi, E.4; Durham, M.1; Ward, J.3; Brooks, J. T.1
Source: Journal of Viral Hepatitis, Volume 18, Number 5, May 2011 , pp. 316-324(
Abstract:
Summary.
Liver disease due to hepatitis C virus (HCV) infection is a leading cause of non-AIDS-related morbidity and mortality in patients infected with HIV. We assessed the frequency of and predictors for initiation of treatment for HCV infection among patients coinfected with HCV/HIV enrolled in the HIV Outpatient Study (HOPS) during 1999-2007. We included patients with confirmed HCV infection, at least 1?year of subsequent follow-up, and no evidence of prior HCV treatment. We assessed predictors of HCV treatment initiation using Cox proportional hazards analyses. During 1999-2007, 103 (20%) HOPS patients coinfected with HCV/HIV initiated HCV treatment during a median of 4.3?years of follow-up (interquartile range: 2.7, 6.7). In multivariable analysis, non-Hispanic black race/ethnicity (hazard ratio HR] 0.3; 95% confidence interval [CI]?=?0.2, 0.6) was independently associated with a lower likelihood of HCV treatment. Elevated alanine aminotransferase (ALT; HR 3.5; 95% CI?=?2.2, 5.6) and CD4+ cell count =500 cells/mm3 (HR 1.8; 95% CI?=?1.2, 2.8) at the start of observation were independently associated with higher likelihood of HCV treatment. For patients starting observation in 1999-2001, 2002-2004 and 2005-2007, 5%, 11% and 21% of patients initiated treatment during the first year of follow-up, respectively. Between 1999 and 2007, despite a stable low fraction of patients coinfected with HCV/HIV initiating treatment for HCV infection, an increasing proportion initiated treatment within the first year after the infection was confirmed. Treatment of HCV infection in patients coinfected with HCV/HIV should be considered a priority, given the increased risk of accelerated end-stage liver disease.
Keywords: HAART; HCV treatment; hepatitis C; HIV HCV; HIV infection; interferon
Document Type: Research article
DOI: 10.1111/j.1365-2893.2010.01299.x
Affiliations: 1: Division of HIV/AIDS Prevention, National Center for HIV, STD and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA 2: Cerner Corporation, Vienna, VA 3: Division of Viral Hepatitis, National Center for HIV, STD and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA 4: Temple University, Philadelphia, PA, USA
Publication date: 2011-05-01
We need results from the studies in India soon followed by the IDE approval for HCV!
http://www.medpagetoday.com/InfectiousDisease/Hepatitis/26472?utm_content=&utm_medium=email&utm_campaign=DailyHeadlines&utm_source=WC&userid=335313
Hi Calcsmart,
Sorry for the delay in the response.
This company from what I know, has a lot going for it :
-an incredible product with broad spectrum applications ranging from Infectious diseases, both acute and chronic, to Cancer. Most companies come out with one product and spend millions in research to develop and test it for one indication and then wait for FDA approval. Imagine having one drug which works very well in a lot of different diseases!!!
The product has already proven to be safe which is a big requirement for FDA approval.
-It has already been demonstrated to be effective in reducing the viral load in a number of different viral infections. The ability of the HP to counteract viral infections is very impressive and according to me that list is currently restricted as the company is rightfully focusing on some of the most common conditions to gain acceptance by the medical profession and some of the conditions which the govt. is focusing on as WMD. Once approved I am sure that MDs will perform studies on other less common but still significant conditions which also drain the healthcare systems substantially. These illnesses though not common as HCV can still be a source of tremendous revenue for AEMD.
-Cancer application for the HP - I feel that although this is very promising, it requires a lot of research. The HP will most likely be an adjuvant to chemotherapy, but how will it be used needs to be studied - every week, every few days, for months to keep the cancer under check once it is under control? A lot more questions, will take a long time as the studies will have to be done for each disease specifically. Once proven to be effective as a part of treatment the revenues the sky would be the limit in terms of revenues.
-Currently the biggest catalyst for the stock should be govt. approval for the HP. I have been looking at the web sites and it is amazing how some of the requirements/ideas from the govt perfectly fit a small company like AEMD. These grants can bring major recognition and revenue to AEMD and also faster FDA approval for the HP, as I did read somewhere that getting BARDA/DARPA approval helps for FDA approval.
All this IMHO.
http://www.medpagetoday.com/MeetingCoverage/DDW/26419?utm_content=&utm_medium=email&utm_campaign=DailyHeadlines&utm_source=WC&userid=335313
-More use for the HP if more cases are diagnosed!
Some interesting points-
-If everyone born from 1946 to 1964 were screened for the virus, about 48,000 fewer HCV-related deaths could be expected in this population, given current patterns of treatment among individuals diagnosed with HCV infection, said Lisa McGarry, MPH, of the research firm Innovus in Medford, Mass.
Another 11,000 lives could be saved by expanding the screening population to include those born from 1965 to 1970, McGarry told attendees here at Digestive Disease Week.
Estimates are that some three-quarters of people with HCV are unaware of it.
These individuals are at high risk to develop liver disease, which may be less responsive to treatment when it has become symptomatic. The result for such people is transplantation and/or death in many cases, she pointed out.
-Adrian Di Bisceglie, MD, of St. Louis University, who moderated the press briefing, said the Department of Health and Human Services is scheduled to release a new action plan on hepatitis virus screening that may recommend changing the scope of HCV screening.
"I think they'll be looking at strategies like this," he said.
Sorry for the typo in message 2170 - BOCEPREVIR!
TELAPREVIR (T)
Studies done with this drug and the results in concise -
ADVANCE trial -
Patients received 12 weeks of T, with 24 or 48 weeks of PEG/RBV, based on response-guided parameters of viral negativity between 4 & 12 weeks. Almost 60% of the patients qualified for the shorter duration of therapy. SVR rates of 75% were achieved.
7% of the patients discontinued T due to rash.
Incidence of anemia upto 40%.
ILLUMINATE trial -
SVR of 72%
REALIZE trial -
SVR of 64%. Complete response to be presented. Pts with a previous relapse had an SVR of 86%, partial responders had a SVR of 57% and null responders 31%.
Bottom line for AEMD - these new drugs are not a cure all for HCV. Both have a lot of limitations which if considered the millions of people who have HCV can translate into a lot of patients who will need other options. Limitations include costs, access to treatment, age, race, other comorbidities like renal disease, HIV, general medical conditions etc.,
BOCEPRVIR (B)
Drug studied in a few trials - results in concise
SPRINT-2 trial- overall SVR rate was 66% ( 68% in non-black & 53% in african americans).
Here PEG/RBV was used for a 4 week lead-in followed by addition of B for 24 weeks. A response- guided therapy paradigm was then used to determine ultimate length of PEG/RBV of 28 wks or 48 wks based on viral negativity at and beyond wk 8.
Overall, approximately 50% of the patients qualified for the shortened duration (28 weeks).
Approx. 25 % reqd. 24 weeks of B and 48 wks of PEG/RBV.
The remaining 25% of patients discontinued due to futility at week 24 or side effects.
RESPOND -2 trial - SVR rates were 66% in the 48 wk arm and 59% in the response guided arm.
25% of the patient in this study had very little interferon response during the initial 4 week lead in. These patients had SVR rates of only 34% compared with upto 79% in patients with some interferon response at the end of lead-in.
Incidence of Anemia upto 50% but discontinuation due to anemia, however, occurred in less than 2% of patients.
Bottom line for HP/AEMD - Still a big chunk of patients who failed the new combination therapy.
New HCV drugs-
Gets technical.
Boceprevir (B) and Telaprevir(T) are the new Direct Acting Antivirals (DAA).
They are serine protease (NS3- NS4A) inhibitors. This serine protease is used by the HCV virus for viral replication. So use of the inhibitors leads to rapid viral decline. However these cannot be used as monotherapy because of rapidly developing resistance. Hence the are used in combination with the current SOC therapy. which is PEG/RBV.
Incidence of HCV increasing -
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6017a2.htm
-The increase in case reports appears to represent an epidemic of HCV infection related to IDU among new populations of adolescents and young adults in Massachusetts.
-Although similar increases in human immunodeficiency virus (HIV) infection were not identified for this age group, increases in reports of HCV infection among injection drug users might be a harbinger of increases in IDU-associated HIV.
-Other states have indicated similar increases in HCV infection among adolescents and young adults. For example, in 2008, New York reported an increase in HCV infection among persons aged <30 years in suburban Buffalo (5). Since that time, surveillance data have indicated continued transmission and possibly new activity in other areas of New York (Elena Rizzo, New York State Department of Health, personal communication, 2011).
-The recent Institute of Medicine report on viral hepatitis and liver cancer noted that younger injection drug users might be at highest risk for seroconversion in the years immediately following initiation of injection practices (2).
-The findings in this report are subject to at least four limitations. First, the surveillance data only include information for persons who have access to and obtain serologic testing and thus might underrepresent the number of persons with HCV infection.
Is AEMD going to be here also?
https://www.medicalcountermeasures.gov/BARDA/PHEMCE/Workshop/2011/workshop.aspx
So this is part of what JJ has been referring to-
http://www.niaid.nih.gov/topics/BiodefenseRelated/Biodefense/research/Pages/CatA.aspx
i-box/intro message updated
HCV (continued)-
Currently, Genotype 1, which is the most common in the US, is the most difficult to treat and requires 48 weeks of treatment. A SVR is achieved in only 40%-45% of the patients.
Genotypes 2 & 3 comprise 25-30% of the infections in the US, usally require 24 weeks of therapy, and have SVR rates of 65 -80%.
Side effects of current SOC often make adherence to therapy difficult, further reducing the chance for a SVR.
Upto 80% of African Americans with type 1 genotype do not respond to current SOC.
HCV in the elderly - In this population antiviral therapy is limited by existing conditions such as hypertension, heart failure, lung disease, diabetes and heart disease.
Also, with the current SOC therapy, the SVR rates are lower in the elderly.
HIV coinfection is not uncommon with HCV, as both the viruses are blood borne. The prevalence of HIV is from 8-19% in patients with HCV. Patients infected with both viruses are more likely to progress to cirrhosis and advanced liver disease.
Also, coinfection with HCV affects the progression of HIV infection, and is independently associated with a 70% increased risk of progression to a new AIDS related event or death.
HCV is the leading non-AIDS-related cause of death in coinfected patients.
The AEMD HP would have a tremendous potential, inspite of new drugs coming to the market soon, for a lot of reasons in my opinion :
- the current SOC may remain the SOC in many places in the world because the cost of the to be approved medications would be too prohibitive. The HP is a cheaper alternative in the US as well as the rest of the world.
- the HP from AEMD would decrease the initial viral load, which is a big factor in improving the SVR and thus the cure, regardless of the genotype, race, age, HIV coinfection, other coexisting illnesses.
- there is no reason that the HP should not decrease the viral load in nonresponders, partial responders or relapsers and thus improve their chances for clearing HCV.
- Killing two birds with one stone? studies need to be done, but the potential of treating both HIV and HCV, byitself would be a huge application for the HP.
- Viral mutation should not be an issue with the HP because of the way it works.
This is where the HP factors in -
Predictors of SVR (with current SOC)
- non-genotype 1
- low baseline viral load
- an RVR at week 4
- (no portal HTN)
- (low serum GGT)
Patients who achieved an SVR had an event-free survival rate at 5 years of 98% versus 59% in nonresponders.
With current SOC, 45% of patients infected with HCV genotype 1( most common in the US) achieve an SVR, whereas 65% of those infected with genotype 2 or 3 do so.
Also, for non-responders extended therpy (upto 72 weeks) is recommended.
Virologic Response in HCV
SVR Sustained Virologic Response
Absence of HCV 24 weeks after discontinuation
therapy.
SVR is also considered a virologic "cure"
RVR Rapid Virologic Response
Undetectable HCV at week 4 of treatment.
Highly predictive of SVR
EVR Early Virologic Response
> 2 log reduction or complete absence of HCV at week
12 of therapy.
Failure to achieve EVR is most accurate
predictor that SVR will not be achieved.
Null Responder - Failure to suppress HCV by 1 log after 4 weeks and <2 logs after 12 weeks of therapy.
Partial nonresponder - HCV levels <2 logs but never undetectable.
Nonresponder - Failure to clear HCV after 24 weeks.
HCV
Some statistics in the previous and this post. If one looks at the big picture it becomes easy to understand why the HP can be a crucial and essential component of the SOC.
-6 major genotypes and atleast 50 subtypes
Most common genotypes in US are 1a and 1b which account for 75% of the cases.
10 - 20% are infected with genotypes 2 and 3
This is important to know because response to current SOC and also the 2 new drugs to be available soon is different in the different genotypes. Infact genotyping is recommended in all patients wisth HCV prior to interferon treatment.
-the virus has a propensity to mutate which may be one of the reasons it is difficult to eradicate.
-Long term complications are Cirrhosis, End-stage liver disease and Liver Cancer.
-People with HIV and HCV both have a higher rate of cirrhosis.
HEP C(HCV)
-most common chronic blood borne infection in the US
-leading cause of cirrhosis and liver transplantation
-According to the CDC (Centers for Disease Control and Preventation) 2.7 - 3.9 million individuals have the chronic infection. It is difficult to assess the prevalence of HCV infection; the asymptomatic nature of acute infection and early chronic infection leaves many infected individuals undiagnosed. Therefore it is estimated that up to 5 million people in the US have HCV.
-Chronic HCV is responsible for 8000 - 12000 deaths each year.
-75%-80% of individuals acutely infected with HCV will progress to chronic infection and 60-70% will develop chronic liver disease.