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Nature Editorial, SEPTEMBER 2010 (more on the same)
The identity problem
http://www.nature.com/nbt/journal/v28/n9/full/nbt0910-877.html
The US Food and Drug Administration (FDA) decision to approve a generic heparin derivative without clinical safety or efficacy data raises the possibility that clinical trials might not always be required for the approval of follow-on biologics.
At the end of July, the FDA granted marketing approval to an anticoagulant, the low-molecular-weight heparin (LMWH) enoxaparin sodium injection. The product, co-developed by Momenta Pharmaceuticals and Sandoz, was approved under generics regulations and was designated equivalent to and substitutable for Lovenox, manufactured by Sanofiaventis. The FDA’s decision to consider enoxaparin under the Abbreviated New Drug Application (ANDA) pathway has raised some eyebrows. It not only runs counter to the established European regulatory framework for biosimilars but also suggests that the FDA might, in some cases at least, not require extensive clinical trials for follow-on biologics.
Enoxaparin is not the first generic biologic approved in the United States. Six other generic biologics have been approved under ANDAs, a major advantage of which is that no clinical trial data are required and products can be designated therapeutically equivalent to a brand. Under this path, FDA can also designate a generic as automatically substitutable for the brand in the pharmacy. Of the biologics, only Lovenox and calcitonin generics have been approved under an ANDA and received brand substitutability status. Sandoz’s Omnitrope (human growth hormone) was licensed using a New Drug Application (NDA) filed under 505(b)2, a regulatory pathway that allows submission of clinical data demonstrating safety and efficacy but does not offer substitutability.
When Momenta filed its ANDA for enoxaparin in August 2005, the challenge facing the FDA was how to demonstrate its therapeutic equivalence to Lovenox. The problem, ostensibly, is that enoxaparin is complex and difficult to define chemically. Its manufacture involves the alkaline depolymerization of heparin from pig intestinal mucosa. Heparin itself is a mixture of linear polysaccharide chains consisting of repeating disaccharide units composed of glucuronic or iduronic acid and N-sulfated or N-acetylated glucosamine; during its depolymerization to enoxaparin, additional distinctive chemical modifications may occur. The resulting final product has a mean molecular mass of 4.5 kDa but consists of polysaccharide chains varying in length, composition and distribution. The brand drug has never been fully characterized, nor has the contribution of its components to therapeutic efficacy been established.
In information that accompanied the approval, the FDA indicated how it compared the brand and generic versions, an assessment with possible implications for other biologics. The agency’s analysis was based on five criteria.
First, the comparison involved gross physicochemical properties (molecular mass distribution and overall chemical composition): the FDA wanted to see that similar oligosaccharide chain lengths were present in the same relative abundance in generic and brand enoxaparin. Second, the drug sources were compared: the source heparin had to have a similar distribution of disaccharide building blocks, and beta-elimination of the heparin benzyl ester had to be shown during depolymerization. A third comparison looked at the products’ molecular nature: besides confirming the presence of a pharmacologically important 1,6-anhydro ring at the ends of 15–25% of enoxaparin chains, the FDA looked at the spectrum of disaccharide building blocks and the oligosaccharide lengths and sequences—factors affected by the temperature, depolymerization time and other conditions of preparation.
Besides these physiochemical analyses, the FDA required not only biological and biochemical assay data to demonstrate equivalentanticoagulant activity in vitro and in vivo but also pharmacodynamic data from healthy human volunteers. Taking all the data together, FDA concluded “that generic enoxaparin will have the same active ingredient components as those of
Lovenox’s enoxaparin (within the context of its variability), even though the contribution of each component has not been fully elucidated.”
As immune reactions, such as pruritus, urticaria and anaphylactic and anaphylactoid responses, have been observed with Lovenox, the agency also requested that manufacturers demonstrate quivalent immunogenicity for generic enoxaparin. Again, it stopped short of requiring clinical studies, accepting data from in vitro and ex vivo assays and from animal studies.
Overall, the generic enoxaparin approval indicates that current analytical technology and integrated, multivariate data analysis can convince the FDA of the equivalence of two complex, biologically derived preparations. The FDA has determined that the product is the same if it meets its criteria of identity (even if the product is not identical)—a substantial departure from European guidelines for LMWH biosimilars designed for products that contain a similar active ingredient. The good news, it seems, is that as long as the FDA is satisfied that the data package sufficiently establishes the sameness of the active ingredient, the need for clinical data diminishes.
The billion-dollar question—as yet unanswered—is whether the FDA will consider similar supporting data for complex biologics approved under the Biologic License Application pathway as sufficient to demonstrate therapeutic equivalence without large clinical trials. As the complexity of the biologic being reproduced becomes greater—from peptides, to hormones and growth factors, and all the way to monoclonal antibodies—the capacity of current technology is likely to approach its limits. In this respect, another generic product may soon provide an answer.
An ANDA for a generic of Copaxone, Teva’s treatment for multiple sclerosis, has been before the FDA since July 2008. Copaxone is perhaps the quintessential complex peptide drug, a heterogeneous mixture containing a huge number of synthetic polypeptides. Its analysis will certainly push the envelope for current technology and illustrates how important sophisticated technical capability will be to sponsors wishing to work in this area.
Even the Copaxone case, though, may still not provide much guidance for recombinant biologics. Like enoxaparin, Copaxone’s complexity largely stems from the active ingredient. In contrast, variation in most recombinant products—and thus the analytical challenge—arises not in the active ingredient but in post-translational modifications, proteolysis, oxidation and aggregation that occur during manufacture, formulation and storage. All of which adds up to a different challenge again.
GM animals - transgenic salmon
Transgenic fish go large
http://www.nature.com/news/2010/100914/full/467259a.html
Approval expected for genetically modified salmon.
By Emma Marris
A genetically modified animal is on the brink of making an appearance on US dinner tables for the first time. The Food and Drug Administration (FDA) is expected to approve a genetically modified (GM) Atlantic salmon that grows twice as fast as wild Atlantics, reaching market weight in a year and a half instead of three. Approval could come as soon as next week.
The fish contains a single copy of a DNA sequence that includes code for a Chinook salmon growth hormone and regulatory sequences derived from Chinook salmon and the eel-like ocean pout. Whereas Atlantic salmon normally stop growing in the winter, the GM fish produces growth hormones throughout the year. Developer AquaBounty Technologies, based in Waltham, Massachusetts, has spent more than a decade shepherding the fish towards approval in a new regulatory landscape. In 2009, the FDA decided to classify GM traits in animals as veterinary drugs. Some have criticized this decision, as it allows companies to shield some details of their product from public view as proprietary information (see Nature doi:10.1038/news.2008.1120; 2010).
To appease critics, the FDA has posted all the information behind its decision on the salmon online, and has opened much of the deliberations of an advisory body — the Veterinary Medicine Advisory Committee (VMAC) — to the public. Next week the VMAC will hold public sessions to hear about the science, safety, environmental impact and possible labelling of the fish. The FDA's Center for Veterinary Medicine, which will decide on approval after hearing from the VMAC, has already released a favourable report.
Some environmental groups are concerned that the fish might escape from their pens and mate with wild Atlantic salmon. "There is always going to be a possibility of escape," says Peter Bridson, aquaculture research manager at the Monterey Bay Aquarium in California. "We would oppose the approval of the current application."
AquaBounty's chief executive Ronald Stotish says those concerns are misplaced. More than 99% of his salmon are triploid, which renders them sterile, and the fish are farmed inland, in large tanks fitted with filters and baffles to imprison eggs, smolt and fish. "The possibility of an escape or an event with any possibility to interact with the wild population is infinitesimal," says Stotish.
According to Mark Abrahams, a biologist at Memorial University in St John's, Newfoundland, Canada, the transgenic fish's ramped-up metabolism is maladapted to life in the wild. "They are willing to incur huge risks to gain access to food," he says, allowing predators to pick off the fish easily.
The next GM animal on dinner plates may be the Enviropig, developed at the University of Guelph, Ontario, Canada, and submitted to the FDA for approval. The pig can better absorb phosphorus from its food, reducing the phosphorus content of its manure. High-phosphorus manure can induce algal blooms in waterways.
There are no requests for authorization of transgenic food animals pending in the European Union, and the European Food Safety Authority, based in Parma, Italy, is just beginning to draft regulatory guidelines. For now, AquaBounty plans to market its salmon only in the United States. "Other countries are interested but they are all looking to the United States for the regulatory imprimatur," says Stotish.
Just to add to what Peter already wrote. I don't think it's a big enough trial to make any real sense. It provides some indication that will need to be verified later if anyone cares to go on with a bigger trial. Also, the authors commented that they do not believe that improvement in lung function by albuterol therapy is the reason for the improved walking time, but did not provide any explanation.
IJ, this group is working on this combo for long time and results from this trial were presented by Dr. Khoury as early as 2008 at WCTRIMS and later at ECTRIMS, ACTRIMS and LACTRIMS and now she published. I will try to get the paper to see if there's anything new because as far as I remember there was a high rate of discontinuations.
FDA panel unanimously recommend approval for FRX' ceftaroline in the CABP and cSSSI indications.
http://finance.yahoo.com/news/FDA-Advisory-Committee-bw-2542658315.html?x=0&.v=1
I think that MRK is trying to say that even though prior nulls were excluded from RESPOND-2 study, since 25% of patients in the trial had < 1 log reduction in viral load at week 4 while in the lead, they might be considered nulls. Still, I don't think nulls will be included in boceprevir's label in opposed to telaprevir.
Give it a rest, comparison like Dew did, as much as one is possible across studies is perfectly fine and we all know the limitations.
On null responder definition - there's more acceptance and I think it will grow, for the “early null responder” who is characterized by <1 log drop in HCV RNA levels at week 4 according to data from the IDEAL study.
The reasons given to the upgrade were: generic Effexor XR, the denial of motion for summary judgment filed by Sandoz/Momenta in the Copaxone patent litigation, and possible near term competition by Gilenia not that bad.
FRX/ceftaroline (apropos to the FDA guidance and ever-changing goalposts)
Phase III program for ceftaroline was initiated in 2007 under the old FDA standards and the primary efficacy endpoint was noninferiority on symptoms resolution at the test-of-cure visit 7-14 days after EOT. Interestingly, the antibiotic was noninferior to the comparator even under the FDA's new efficacy criteria - cessation of spread of the lesion along with absence of fever at day 3.
Briefing docs:
http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/Anti-InfectiveDrugsAdvisoryCommittee/UCM224656.pdf
US FDA staff: Forest antibiotic seems effective
http://www.reuters.com/article/idCNN3127328720100902?rpc=44
* FDA staff back safety, efficacy of ceftaroline
* Advisory panel to review drug on Tuesday
* Forest shares up 5.4 pct in afternoon
* Nearly $361 million in ceftaroline sales seen in 2014
By Lisa Richwine
WASHINGTON, Sept 2 (Reuters) - A Forest Laboratories Inc (FRX.N) antibiotic appears effective with risks similar to current options, U.S. drug reviewers said in an analysis that raised hopes for the medicine's approval.
Shares of Forest, which needs new medicines to offset looming patent expirations on its major drugs, were up $1.49 or 5.4 percent at $29.14 on the New York Stock Exchange after the Food and Drug Administration released its preliminary review on Thursday.
Analysts expect nearly $361 million in sales in 2014 for the potential new antibiotic called ceftaroline, according to Thomson Reuters forecasts.
An FDA advisory panel will review the drug at a public meeting on Tuesday. A positive vote would move the medicine closer to the U.S. market.
In a 70-page analysis released on Thursday, FDA staff said ceftaroline seemed effective for fighting serious skin infections and pneumonia. Potential side effects were similar to alternative treatments, they said.
"FDA appears to go into the panel with a positive bias toward approval" for both conditions, Robert W. Baird analyst Thomas Russo said in a research note. He predicted the stock would close $1 to $2 higher on Thursday.
Ceftaroline is one of six medicines in late-stage development that Forest says will more than replace the coming revenue losses from patent expirations on flagship antidepressant Lexapro and Alzheimer's treatment Namenda.
The company reported net revenue of nearly $4.2 billion for the fiscal year ended March 31.
Ceftaroline is an intravenous antibiotic developed to fight serious and possibly life-threatening infections including methicillin-resistant Staphylococcus auereus (MRSA), a growing public health threat.
FDA staff analyzed Forest's data from two clinical trials in adults with bacterial pneumonia acquired outside a hospital setting. The agency reviewers said their analysis "supported the efficacy conclusions" from Forest that the drug worked as well as an older antibiotic, ceftriaxone.
The drug also appeared equivalent to a combination of the antibiotics vancomycin and aztreonam in two studies of adults with complicated skin infections, FDA staff said.
Ceftaroline is a new medicine in the cephalosporin class of antibiotics that have been used for decades.
The most common possible side effects include diarrhea, headache, nausea and insomnia.
In a separate summary prepared for the advisory panel, Forest said new antibiotics were needed to fight resistant infections that do not respond to current treatments.
"Ceftaroline addresses these distinct areas of unmet medical need," the company said.
The FDA will consider the advisory panel's input when it decides in the coming weeks whether to approve the drug. The agency usually follows panel recommendations.
Forest obtained rights to ceftaroline with its 2007 purchase of privately held biotech company Cerexa Inc. Swiss drugmaker AstraZeneca (AZN.L) is co-developing the drug in markets outside the United States, Canada and Japan. Takeda Pharmaceutical Co (4502.T) holds the rights in Japan.
The European Commission has granted marketing authorisation for Shire's VPRIV
http://www.checkorphan.org/grid/news/treatment/shire-announces-european-approval-of-vpriv-r-velaglucerase-alfa-for-the-treatment-of-type-1-gaucher-disease
Scientific Meeting Calendar
NOTE: ANYONE MAY UPDATE THIS FILE
Edits: Deleted old entries; Added ASBD, ECTRIMS, ESMO, ASBMR
SEPTEMBER 2010
International Symposium on Hepatitis C Virus and Related Viruses
Yokohama, Japan
September 10-14, 2010
http://www.hcv2010.jp/
Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC)
Boston
September 12-15, 2010
http://www.icaac.org/
American Neurological Association - ANA
San Francisco
September 12-15, 2010
http://www.aneuroa.org/i4a/pages/index.cfm?pageID=3311
The Society for Hematology and Stem Cells - ISEH
Melbourne, Australia
September 15-18, 2010
http://www.iseh.org/i4a/pages/index.cfm?pageid=3431
European Respiratory Society - ERS
Barcelona, Spain
September 18-22, 2010
http://www.erscongress2010.org/
European Association For the Study of Diabetes - EASD
Stockholm
September 20-24, 2010
http://www.easd2010.com/
Transcatheter Cardiovascular Therapeutics - TCT
Washington, D.C.
September 21-25, 2010
http://www.tctconference.com/
International Society of Hypertension - ISH
Vancouver, Canada
September 26-30, 2010
http://www.ish-world.com/default.aspx?Home
OCTOBER 2010
American Society of Breast Disease, Breast Cancer Symposium - ASBD
San Francisco, CA
1-3 October, 2010
http://www.breastcasymposium.org/
European Society for Medical Oncology Congress - ESMO
Milan, Italy
8-12 October, 2010
www.esmo.org/
European Committee for Treatment and Research in Multiple Sclerosis - ECTRIMS
Gothenburg, Sweden
13-16 October, 2010
http://www.congrex.ch/index.php?id=77
American Society for Bone and Mineral Research - ASBMR
Toronto, Canada
15-19 October, 2010
http://www.asbmr.org/
American Association for the Study of Liver Diseases - AASLD
Boston
October 29 - November 2, 2010
http://www.aasld.org/
NOVEMBER 2010
American Society of Human Genetics - ASHG
Washington, DC
November 2-6, 2010
http://www.ashg.org/
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Form 8-K for PROTALIX BIOTHERAPEUTICS, INC.
16-Aug-2010
Other Events
Item 8.01. Other Events
On August 10, 2010, Pfizer Inc. ("Pfizer") entered into a $30 million [PLX share will be $12M] short-term supply agreement with the ministry of health of a Latin American country [probably Brazil] pursuant to which Protalix BioTherapeutics, Inc. and Pfizer will provide taliglucerase alfa to Gaucher disease patients in such country. ... snip
Hehe, that's a good one! although I do think their technology is (I should probably use past tense here) exciting. Sorry for the spelling mistake. I used to have an editor but he is too busy these days...
Gene testing could have saved weight-loss drug
http://www.reuters.com/article/idUSN1220142320100812
* Genomics could have kept Acomplia on market - study
* Finding points way to better drug development
By Julie Steenhuysen
CHICAGO, Aug 12 (Reuters) - Genetic testing might have helped identify people who would become depressed or suicidal while taking Sanofi-Aventis' (SASY.PA) weight loss drug Acomplia, which might have helped keep the drug on the market, U.S. researchers said on Thursday.
They said partial results from a study of the drug in which five people committed suicide confirmed that it increased the risk of psychiatric side effects.
The study was halted in 2008 and the company pulled the drug from the market in Europe, but the researchers think genetic testing might have been able to identify people who were at risk of the side effects, and rescue the once-promising treatment, said Dr. Eric Topol of Scripps Translational Science Institute in La Jolla, California, whose study appears in the journal Lancet.
Acomplia, known generically as rimonabant, blocks the same reward receptors in the brain that become active during marijuana use, and for some people, it caused serious bouts of anxiety and depression that led to suicide.
"Finding the gene for severe adverse drug reactions is a lot easier than we ever thought it would be," Topol said in a telephone interview.
Topol thinks if they had thought to collect genetic information on the study's more than 18,000 participants, they might have spared the drug.
"We probably could have figured out genomically who was susceptible and that drug could be quite viable," Topol said in a telephone interview.
Hopes had been high for Acomplia, which not only helped people lose weight but helped them achieve more normal blood sugar levels and improvements in blood fats known as triglycerides and HDL cholesterol, the so-called good cholesterol.
In Topol's study, which looked at the heart benefits of the drug, four patients taking rimonabant and one person taking a placebo committed suicide.
Of the results they had, they found deaths from heart disease, heart attacks and strokes occurred at similar rates in both groups, and they did find that serious psychiatric side effects were increased in rimonabant users compared with placebo.
Due to these side effects, the European Medicines Agency recommended doctors no longer prescribe rimonabant from October 2008. Concerns about side effects prevented the drug from winning U.S. regulatory approval.
Topol says it is likely too late to revive Acomplia, but he said the study does offer insights about how to avoid similar problems with drugs in the future.
"Genomics could potentially be used to pre-empt use of the drug in individuals with risk of serious adverse events," he said in a statement.
last time I took Jeffrey Shuren for lunch he said they are primarily after direct-to-consumer genetic tests, so I think MYGN tests are safe :)
Colaris (colorectal and uterine cancer risk) and Colaris AP became commercially available in the U.S. in 2000 and 2002 respectively. Theraguide for predicting adverse events from 5-FU, was launched in July 2007, so perhaps it needs a couple of more years.
MYGN/Colaris test
I would wait until I see data from phase III trial against warfarin for stroke prevention in AF setting (ROCKET-AF)
http://clinicaltrials.gov/ct2/show/NCT00403767?term=xarelto&phase=2&rank=3 mainly because of the tendency for increased bleeding.
Found this free full text review from Oct. 2009 - The new oral anticoagulants.
Don't know if it was posted already.
http://bloodjournal.hematologylibrary.org/cgi/content/full/115/1/15#T4
GTCB indeed has an exiting technology and choose the wrong product but from all they had at that time combined with the problem it takes 15 years from conceiving an idea in transgenic technology till maturation plus you cannot afford developing other candidates in parallel, it was the more sexy one. Too bad.
One more for that list is Astellas YM-150:
Source: http://www.astellas.com/en/ir/library/pdf/1q2011_pre_en.pdf
MYGN
BRACAnalysis accounted for $82.5M which is nearly 88% of total revenues ($93.9M) for the 4Q10.
http://investor.myriad.com/releasedetail.cfm?ReleaseID=498131
More work from ADNI grant on CSF biomarkers of Alzheimer's disease:
Diagnosis-Independent Alzheimer Disease Biomarker Signature in Cognitively Normal Elderly People
http://archneur.ama-assn.org/cgi/content/abstract/67/8/949?maxtoshow=&hits=10&RESULTFORMAT=&fulltext=Trojanowski&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT
De Meyer et. al.
Objective
To identify biomarker patterns typical for Alzheimer disease (AD) in an independent, unsupervised way, without using information on the clinical diagnosis.
Design
Mixture modeling approach.
Setting
Alzheimer's Disease Neuroimaging Initiative database.
Patients or Other Participants
Cognitively normal persons, patients with AD, and individuals with mild cognitive impairment.
Main Outcome Measures
Cerebrospinal fluid–derived ß-amyloid protein 1-42, total tau protein, and phosphorylated tau181P protein concentrations were used as biomarkers on a clinically well-characterized data set. The outcome of the qualification analysis was validated on 2 additional data sets, 1 of which was autopsy confirmed.
Results
Using the US Alzheimer's Disease Neuroimaging Initiative data set, a cerebrospinal fluid ß-amyloid protein 1-42/phosphorylated tau181P biomarker mixture model identified 1 feature linked to AD, while the other matched the "healthy" status. The AD signature was found in 90%, 72%, and 36% of patients in the AD, mild cognitive impairment, and cognitively normal groups, respectively. The cognitively normal group with the AD signature was enriched in apolipoprotein E {varepsilon}4 allele carriers. Results were validated on 2 other data sets. In 1 study consisting of 68 autopsy-confirmed AD cases, 64 of 68 patients (94% sensitivity) were correctly classified with the AD feature. In another data set with patients (n = 57) with mild cognitive impairment followed up for 5 years, the model showed a sensitivity of 100% in patients progressing to AD.
Conclusions
The mixture modeling approach, totally independent of clinical AD diagnosis, correctly classified patients with AD. The unexpected presence of the AD signature in more than one-third of cognitively normal subjects suggests that AD pathology is active and detectable earlier than has heretofore been envisioned.
Makes sense. Also, AEs and discontinuations were as expected. So overall the study did achieve its purpose and showed the majority of patients can get the shorter 24-week treatment.
And don't ignore the huge 20 CSF samples :)
It sure sounds like they were thinking: great, the lower dose might not kill anyone and although this arm alone isn't powered to show stat-sig on efficacy we do have CSF samples of 20 patients demonstrating a biological effect on amyloid-beta.
I wouldn't go that far. I meant strange as I have no explanation.
Strange (in the sense that it is opposed to what I'd expect), that patients in the shorter treatment arm had higher SVR rate but higher relapse rate than the longer 48 weeks arm.
VRTX/ILLUMINATE trial
Phase 3 ILLUMINATE Study Supports 24-Week Telaprevir-Based Therapy Within a Response-Guided Regimen for People with Hepatitis C Who Had Not Received Prior Treatment
http://finance.yahoo.com/news/Phase-3-ILLUMINATE-Study-bw-3201562659.html?x=0&.v=1
Press Release Source: Vertex Pharmaceuticals Incorporated On Tuesday August 10, 2010, 7:00 am EDT
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX - News) today announced results from the Phase 3 ILLUMINATE study, which was designed to evaluate whether there was any benefit to extending therapy from 24 to 48 weeks in people whose hepatitis C virus (HCV) was undetectable at weeks 4 and 12 of treatment (extended rapid viral response or eRVR). People in the trial who met these eRVR criteria and who remained on treatment were then randomized at week 20 to receive 24 or 48 weeks of total treatment. People who did not meet these criteria were assigned to 48 weeks of pegylated-interferon and ribavirin therapy.
Sustained viral response (SVR or viral cure) rates of 92% and 88% were observed in the randomized 24 and 48-week telaprevir-based treatment groups, respectively. 72% of all 540 people treated with telaprevir in the study achieved a viral cure. The safety and tolerability profile of the telaprevir-based regimen was consistent with results reported previously from the pivotal Phase 3 ADVANCE study.
“The viral cure rates seen in ILLUMINATE showed that there was no benefit to extending telaprevir-based therapy to 48 weeks for the majority of people,” said Kenneth Sherman, M.D., Ph.D., Professor of Medicine at the University of Cincinnati College of Medicine, Director of the Division of Digestive Diseases for UC Health and Principal Investigator of the trial. “Patients who had a rapid response to telaprevir-based regimens at weeks 4 and 12 had a high likelihood of achieving a cure with 24 weeks of total treatment, which may provide important information to motivate people to continue therapy.”
“Data from ILLUMINATE and ADVANCE support our belief that the use of 24-week telaprevir-based therapy within a response-guided regimen may provide an important future treatment option for people with hepatitis C,” said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer for Vertex.
Telaprevir is an investigational, oral inhibitor of HCV protease, an enzyme essential for viral replication, and is being developed by Vertex Pharmaceuticals in collaboration with Tibotec Pharmaceuticals and Mitsubishi Tanabe Pharma. Results from the ILLUMINATE study are expected to supplement data obtained from ADVANCE and REALIZE - the two pivotal Phase 3 studies of telaprevir - as part of a New Drug Application submission to the U.S. Food and Drug Administration planned for the fourth quarter of 2010.
Efficacy Results from ILLUMINATE
Primary analysis for people who met certain response criteria*:
24-week telaprevir-based treatment regimen:
* SVR Rate: 92% (149/162)
* Relapse Rate: 5.7% (9/159)
48-week telaprevir-based treatment regimen:
* SVR Rate: 88% (140/160)
* Relapse Rate: 1.9% (3/154)
*Reflects people whose hepatitis C virus was undetectable (<25 IU/mL and undetectable by Roche COBAS Taqman HCV test) at weeks 4 and 12 (eRVR) and who remained on treatment through week 20.
Overall efficacy analysis for all patients treated with telaprevir in ILLUMINATE (ITT or intent-to-treat analysis):
* SVR Rate: 72% (388/540)
* Relapse Rate: 7.7% (36/469)
* Rapid Viral Response (RVR) Rate: 72% (389/540)
* Extended RVR (eRVR): 65% (352/540)
Safety & Tolerability Results from ILLUMINATE
The safety and tolerability profile of the telaprevir-based regimen in the ILLUMINATE study was similar to results reported from the Phase 3 ADVANCE study. The most common adverse events reported in the ILLUMINATE study, in order of frequency, were fatigue, pruritus, nausea, anemia, rash and headache. The majority of these adverse events were mild or moderate. Adverse events leading to discontinuation of all study drugs during the 12-week telaprevir dosing period occurred in 6.9% of people in the study. Treatment discontinuation of all drugs due to anemia and rash occurred in 1.1% and 0.6% of people in the study, respectively, during the telaprevir dosing period. Like in ADVANCE, the use of erythropoiesis-stimulating agents (ESAs) was not allowed in this study.
Data from ILLUMINATE have been submitted for presentation at the 2010 Annual Meeting of the American Association for the Study of Liver Diseases.
About the ILLUMINATE Trial
ILLUMINATE was a Phase 3, supplemental, open-label, randomized study in people infected with genotype 1 chronic hepatitis C, the most common form of the virus in the U.S. and Europe, who had not been previously treated (treatment-naïve). In this study, people who met protocol-defined response criteria of achieving eRVR were randomized at week 20 to receive 24 or 48 weeks of total treatment. The primary endpoint of the study was the proportion of patients who achieved SVR in the randomized treatment groups, and evaluated by a non-inferiority analysis. Based on this analysis, the study achieved its primary endpoint of non-inferiority with respect to SVR rates in the randomized 24 and 48-week telaprevir-based arms. The trial enrolled people at 76 clinical trial sites in the U.S. and Europe. A greater proportion of people in the ILLUMINATE study (approximately 90%) were enrolled at U.S. sites compared to the proportion in ADVANCE. As in all studies evaluating telaprevir-based regimens, patients received no more than 12 weeks of triple therapy (telaprevir, pegylated-interferon and ribavirin) followed by pegylated-interferon and ribavirin only, as part of either 24 or 48 weeks of total treatment, as noted in the trial design.
Scientific Meeting Calendar
NOTE: ANYONE MAY UPDATE THIS FILE
Edits: Removed old entries; Added HCV2010, ANA, ERS, EASD, TCT, ISEH, ISH
AUGUST 2010
American Society of Retina Specialists - ASRS
Vancouver, Canada
August 28 - September 1, 2010
http://www.asrs.org/
European Society of Cardiology - ESC
Stockholm, Sweden
August 28 - September 1, 2010
http://www.escardio.org/congresses/esc-2010/Pages/welcome.aspx
World Congress On Pain - IASP
Montreal, Canada
August 29 - September 3, 2010
http://www.iasp-pain.org//AM/Template.cfm?Section=Home
SEPTEMBER 2010
International Symposium on Hepatitis C Virus and Related Viruses
Yokohama, Japan
September 10-14, 2010
http://www.hcv2010.jp/
American Neurological Association - ANA
San Francisco, CA
September 12-15, 2010
http://www.aneuroa.org/i4a/pages/index.cfm?pageID=3311
The Society for Hematology and Stem Cells - ISEH
Melbourne, Australia
September 15-18, 2010
http://www.iseh.org/i4a/pages/index.cfm?pageid=3431
European Respiratory Society - ERS
Barcelona, Spain
September 18-22, 2010
http://www.erscongress2010.org/
European Association For the Study of Diabetes - EASD
Stockholm, Sweeden
September 20-24, 2010
http://www.easd2010.com/
Transcatheter Cardiovascular Therapeutics - TCT
Washington, D.C.
September 21-25, 2010
http://www.tctconference.com/
International Society of Hypertension - ISH
Vancouver, Canada
September 26-30, 2010
http://www.ish-world.com/default.aspx?Home
OCTOBER 2010
American Association for the Study of Liver Diseases - AASLD
Boston, Massachusetts
October 29 - November 2, 2010
http://www.aasld.org/
NOVEMBER 2010
American Society of Human Genetics - ASHG
Washington, DC
November 2-6, 2010
http://www.ashg.org/
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I'm sure he doesn't need an extra pair :)