Vaccibody's lead therapeutic DNA vaccine, developed for the treatment of precancerous changes in the cervix caused by human papillomavirus (HPV) infection, is expected to move into the clinic in late 2013 once funding is in place, the company CEO Ole Henrik Brekke told FierceVaccines at BIO 2012. The trial will recruit women who are infected with HPV-16 and have cervical intraepithelial neoplasia (CIN) at grade 1 or 2.The Norwegian vaccine company has designed the vaccine to trigger a T cell response in a single shot by targeting the dendritic cells (also known as antigen-presenting cells). The HPV vaccine is administered just under the skin or into the muscle using electroporation technology, where a small charge allows the plasmid (a small circle of coding DNA) into the cell. The genetic information then harnesses the cell's manufacturing capabilities to create the three-component protein vaccine."We see a higher immune response than other DNA vaccines in animal studies, and it doesn't need an adjuvant," says Brekke. "We think that this is because the vaccine molecules adhere to the dendritic cells."Future formulations of the vaccine could use needle-free administration techniques. The technology also has potential for infectious disease and in veterinary use, as a prophylactic vaccine, and the company is in discussion with a number of potential partners, according to Brekke.- read the company overview at BIO 2012Related Articles:
GeoVax: Meeting the HIV vaccine challenge
DNA vaccine swats TB and HIV
Army uses ducks and DNA vax to make antivirals
Scancell's DNA melanoma vaccine poised for Phase II
DNA vaccine for prostate cancer moves into Phase III read more..
Friday, 22 June 2012
Cervical Intraepithelial Neoplasia-Human Papillomavirus-Prophylactic Vaccine-Dendritic Cells
Government Of India-Cervical Cancer-Clinical Trial-Andhra Pradesh-Hpv Vaccine
Human papillomavirus infection is the cause of nearly all cases of cervical cancer, and so immunizing young women before they are exposed to the virus could save a great many lives. So, the idea of a large scale clinical trial of an HPV vaccine in India seems like a valid idea, based on the country's supposed huge cervical cancer healthcare burden. Not so--according to a paper published in the Journal of the Royal Society of Medicine, the epidemiology behind the study is flawed and the trial is currently the subject of an investigation by the Indian government.The trial was under the auspices of PATH, an international health charity, and included over 23,000 girls in the Indian states of Gujarat and Andhra Pradesh. The charity had claimed that "in raw numbers, India has the largest burden of cancer of the cervix of any country worldwide." However, according to the study, led by Allyson Pollock of Barts and The London Medical School, the cancer surveillance, registration and monitoring in India in general, particularly in the Gujarat and Andhra Pradesh regions, were incomplete, so that it would be impossible to tell whether the vaccine would be successful in preventing the disease.The figures that do exist for India show that there were only 22 cases of cervical cancer per 100,000 in 2004/2005 in india, falling from 43 cases per 100,000 in 1982/1983--this is around half the rate in countries like Brazil and Zimbabwe."This trial has clearly raised serious concerns for the people and government of India," says Pollock. "We found that current data on cervical cancer incidence do not support PATH's claim that India has a large burden of cervical cancer or its decision to roll out the vaccine program."India does have major health burdens, for example in malaria and other infectious diseases, maternal anemia and malnutrition, and so the use of an expensive HPV vaccine, which is one of the more expensive vaccines on the market, for a health issue with a lower impact would seem to be a flawed use of limited financial resources.- read the press release
- see the paperRelated Articles:
GAVI Alliance could be closer to HPV vax deal
Gardasil could cut cancer in women already infected with HPV
Study: Most girls who get HPV vax say they see need to practice safe sex read more..
Monday, 14 May 2012
Drug Withdrawal Symptoms-Antidepressant Drugs-Moderate Depression-Clinical Trials
I was just checking out on line yesterday's "60 Minutes" segment--
http://www.cbsnews.com/video/watch/?id=7399362n&tag=contentBody;storyMediaBox
--that features a friend, Dr. Irving Kirsch of Harvard, a psychologist whose work on placebo effect and expectancy I have long admired. But the segment is only peripherally about placebo effect; it's rather about Kirsch's now oft-repeated finding that except for severe depression, the difference between antidepressants and placebos in clinical trials is negligible.
As seems typical, the news program featured as "gosh golly gee whiz" news stuff that we've been over in this blog many times before:
If I had any major quibble with the program, it was that the magic words "side effects" were first mentioned at around 11:30 of the 13:40 segment (by the British psychiatrist). Those words tell the whole story. Placebos might be equivalent to drug in regards to benefits--but certainly not with regard to adverse reactions. We have been incredibly slow (aided by aggressive drug company marketing) to realize in medicine that most of these "nonaddictive" drugs actually have serious withdrawal syndromes, such that the worsening symptoms when patients go off their antidepressants--interpreted by the drug companies as sure proof that they work--might just as well be drug withdrawal symptoms as recurrence-of-depression symptoms.
The other fun part of the program was watching the US psychiatrist (and of course, consultant for several drug firms) who was put on to defend the track record of these drugs. He naturally made no mention of side effects whatever, but he did insist that in his own independent studies, 14% of moderately depressed patients do better on drug than on placebo. (He admitted that it was a wash in mild depression.) In his mind this justified current practice. Can you believe it--14%??? For a condition where the drugs have serious side effects and where talk therapy or exercise work as well? And that's apparently the best rebuttal the drug industry can come up with?
I must here repeat the usual disclaimer--don't try this at home--if you're depressed see your doctor and do what the doctor says, and above all don't discontinue any drug without the doctor's advice. read more..
Sunday, 13 May 2012
Pharmaceutical Companies-Research And Development-Pharmaceutical Company-Direct Marketing
Big pharmaceutical companies are drastically cutting back on research and development. The economics just do not support the model that has been the driving force of the drug industry over the past 15 years.
According to a Forbes analysis reported by Matthew Herper, "The average drug developed by a major pharmaceutical company costs at least $4 billion, and it can be as much as $11 billion" (see "The Truly Staggering Cost Of Inventing New Drugs").
Some pundits suggest that lowering the cost of performing clinical trials will help get more drugs to market faster. Andrew von Eschenbach, former FDA Commissioner and now employed as chairman of conservative think tank Manhattan Institute's Project FDA initiative, suggested that instead of the FDA asking pharma companies to complete "laborious clinical trials proving efficacy, after proof of concept and safety testing, the product could be approved for marketing with every eligible patient entered in a registry so the company and the FDA can establish efficacy through post-market studies" (see here).
However, Herper points out that the "main expense is failure. AstraZeneca (AZ) does badly by this measure because it has had so few new drugs hit the market." AZ spent about $59 billion on R&D between 1997 and 2011, but only managed to get 5 new drugs approved. According to simple arithmetic, that means each of these 5 drugs cost about $11.8 billion to develop.
That's an interesting number. A very similar number came up during last night's 60 Minutes segment on "Treating Depression: Is there a placebo effect?" (see it here). It turns out that antidepressants sales in the U.S. bring in $11.3 billion a year to pharmaceutical companies that sell them -- including AstraZeneca!
Could it be that the drug industry is merely "breaking even" in the anti-depressant market?
I suspect they are probably making a pretty good profit -- but that profit may be diminishing as more and more anti-depressants go off patent. In fact, it has been suggested that 60 Minutes dared to air this expose -- four years after the research was first published -- because the "news" can no longer harm the drug companies that CBS depends upon for advertising -- most of the drugs mentioned are off patent (see “You’re telling me this now?” Why the news is suddenly critical of statins and antidepressants).
I did a blog post about antidepressants and the placebo effect two years ago in January 2010 (read "A Common Goal of Research and Marketing: Fool the Doctor"). In that post, it was noted that clinical evidence suggests these drugs are not any more effective than a placebo in patients with less severe depression. But drug company marketing to physicians does not mention this. Thus, physicians are led to believe that the drugs ARE effective for all patients with depression.
As pointed out in the 60 Minutes piece, "a clinician who cares, who takes the time, who listens to you, who asks questions about your condition and pays attention to what you say, that's the kind of care that can help facilitate a placebo effect." That goes double if the clinician actually believes what he or she is prescribing is a drug with proven efficacy.
Consequently, marketing to physicians along with direct marketing to consumers can play a huge role in "facilitating" a placebo effect. Which leads me to this idea: pharmaceutical companies should be in the business of developing placebos rather than dangerous, ineffective chemical compounds. There would be no need for expensive clinical trials and it would be easy for FDA to adopt von Eschenbach's idea to approve these new "drugs" before they are proven effective. It will be up to marketing to make them effective by facilitating the placebo effect!
Of course, to be successful, this new approach to drug development must be done surreptitiously and the FDA must conspire with the drug industry (not too much of a stretch there). After all, if everyone kn read more..
Sunday, 29 April 2012
Hoag Memorial Hospital Presbyterian-Brain Cancer Vaccine Trial-Northwest Biotherapeutics
Another site in the U.S., Hoag Memorial Hospital Presbyterian in Orange County, CA, has begun recruiting for a Phase II clinical trial of Northwest Biotherapeutics' ($NWBO) DCVax-L personalized brain cancer vaccine for the treatment of glioblastoma multiforme, the most aggressive and lethal form of brain cancer. By the end of February 2012, Northwest Biotherapeutics had 30 sites open and recruiting in the U.S., and the company plans for 40 by the end of the second quarter. DCVax-L is made from the patient's blood and tumor tissue. In January 2011, FierceVaccines reported that Northwest Biotherapeutics had restarted recruitment into Phase II trials after a two-year postponement, because of the company's cash issues. Press release read more..
Tuesday, 17 April 2012
University Of South Florida-Florida State University-Antidepressant Drug-Drug Development
TAMPA A promising antidepressant drug developed at the University of South Florida and sought by major pharmaceutical firms conjured dreams of vast royalties akin to Gatorade enriching the University of Florida."We all know Gatorade, and we all know some of the big names" of cash-cow products spun out of university labs, Karen Holbrook, then USF's vice president for research and innovation, said back in 2009 when the university's drug caught industry attention. "One of those is hitting the University of South Florida."But things have not gone as hoped. Clinical trials of the USF drug known as "TC-5214" are a bust, dashing the university's vision of a commercial blockbuster, a royalty home run and R&D bragging rights among the nation's big research universities. Gatorade has delivered close to $12 million a year and more than $150 million overall to UF in royalties. Another drug that did succeed in reaching the market, the cancer drug Taxol developed at Florida State University, generated $65 million in FSU royalties in just 2000, though sums have since dropped with the rise of generic drugs.Breakthroughs in university research that hit commercial paydirt are rare. USF's experimental TC-5214, which specifically was being tested as a secondary drug to augment the effects of a primary antidepressant drug, smacked of such potential."This was the biggest thing of financial potential to come out of USF," said Valerie McDevitt, the university's assistant vice president of patents and licensing. "It would have been great if it had succeeded."But when it comes to drug development and clinical trials, there are very few Taxols at the end of the day. We hope one of them will be ours."Two drug companies seeking to develop TC-5214 — Targacept and its much bigger partner, AstraZeneca PLC — recently scrapped plans to develop the drug and win federal FDA approval. It was one of Targacept's lead product candidates.TC-5214 affects the same neuron receptors as nicotine. But it failed in the drug company tests to show a substantial increase in the standard measurement for depression — the Montgomery-Asberg Depression Rating Scale — compared to a placebo.For North Carolina's Targacept, which has patent agreements on the drug with USF, the poor performance of TC-5214 contributed to devastating financial results. Since Nov. 8, Targacept shares have dropped nearly 80 percent. Shares closed Friday at $4.40, down from nearly $20 a share in early November.The 150-employee company added about 35 employees in the past 18 months, some on the assumption of commercializing TC-5214. Further, the company recently learned its top shareholder, The baupost Group LLC of Boston, had sold its entire stake in Targacept holdings of 6 million shares.AstraZeneca has also taken its lumps. In December 2009, it announced it would make a $200 million payment to Targacept to begin a joint effort to develop the drug. Last month, AstraZeneca said it will write off $50 million tied to the failed trials with TC-5214.USF's McDevitt emphasized that TC-5214 may still have potential as a future drug, and it will be up to the drug companies to decide what alternative testing may be considered."I do not think this is over," she said.Paul Sanberg, USF vice president of research and innovation and one of the patent holders on TC-5214, acknowledged the drug did not work for the application pursued by the drug companies. But he stated the drug and its licensing agreement was a bigger story than that in terms of developing a mechanism to help the brain. Sanberg was traveling in China last week and relayed his remarks through a USF spokesman. He did not respond directly to an email seeking more detail."I think we are just starting to see the university become more mature," McDevitt said Friday. "Some of these drug developments can take 10 years just to get where we are. This is a natural progression."Despite the disappointment, the bigger message seems clear: Don't count USF out of th read more..
Sunday, 8 April 2012
Pfizer Announced Plans-Pfizer, Social Media -Personal Technology-Clinical Trial
Last year, Pfizer announced plans to run the first clinical trial to allow patients to participate from home by using computers and smartphones instead of going to a clinic or doctor’s office. The idea was to create a model for saving money that will rely on personal technology to more easily recruit patients and monitor [...] read more..
Monday, 2 April 2012
Autoimmune Disease-Hpv Vaccination-Cancer In Women-Vulvar Disease-Hpv Infection
Merck's ($MRK) Gardasil is used for its ability to protect women and girls against HPV infection. However, it seems as if it may also help some women who are already infected. In fact, data from a study published in the British Medical Journal demonstrate women who are diagnosed with and treated for HPV-related disease may have a considerably reduced risk of reoccurring disease if they have had the shot.The study looked at the 1,350 women who were vaccinated in the FUTURE I and FUTURE II studies and then diagnosed with HPV-related vaginal or vulval diseases (including genital warts) or had cervical surgery. Previous studies have shown vaccination doesn't lower a woman's chance of developing cervical pre-cancers if she had an HPV infection at the time of vaccination. However, this study showed that for women who had cervical surgery after the trials, the chance of developing another bout of HPV-related disease was almost halved. For women with vaginal or vulvar disease, the risk of another HPV disease was cut by around a third.According to the authors, only long-term surveillance can determine the effectiveness of the vaccination in this population. There are a number of ongoing trials to look at the safety and impact of HPV vaccines on subsequent diseases.Still, "[t]he current study moves us closer to understanding the full scope of benefits from HPV vaccination by showing for the first time that vaccine protection against disease can endure beyond the management of HPV related disease in women already vaccinated," states Jane Kim, assistant professor of health decision science at the Harvard School of Public Health, in the BMJ editorial. However, she adds it's too early to generalize from these results. To find out more about the value of Gardasil in women who are already infected will take more and longer studies, but this one does show a glimmer of hope.- get more from the BMJ
- see the abstract in the BMJ
- check out the editorial in the BMJ (reg. req.)
- follow-up the article in Medscape Medical News (reg. req.)
- read the piece in CNN HealthRelated Articles:
Study: Gardasil does not cause autoimmune disease
Gardasil bests Cervarix in cost effectiveness battle
FDA rejects Merck's Gardasil for women over 26
Study: Gardasil effective in boys, men
HPV shot provides sustained protection against pre-cancerous growths read more..
Wednesday, 14 March 2012
Clinical Trials-Pharmalot-Pfizer
After Years of Telling Consumers Not to Trust the Internet, Pfizer Discovers that It Cannot Convince Patients to Participate in Internet-based Clinical Trials. Duh!
As reported on Pharmalot (here): "Last year, Pfizer announced plans to run the first clinical trial to allow patients to participate from home by using computers and smartphones instead of going to a clinic or doctor’s office. The idea was to create a model for saving money that will rely on personal technology to more easily recruit patients and monitor their progress. Known as a ‘clinical trial in a box,’ the study is testing the Detrol overactive bladder drug in 10 states and gained an FDA blessing. However, Pfizer ran into some snags winning over patients."
Craig Lipset, Head of Clinical Innovation at Pfizer, explained it this way: "I think some of the staunch advocates for using online and social media for recruitment are still reticent to claim silver bullet status and not use conventional channels in parallel. In terms of health literacy, the patient population is largely unaware of clinical trials and participation. You’re going in at a level where there’s still a lot of basic learning needed for individuals to make informed decisions about whether to participate. And doing that without an interaction with a healthcare provider is a challenge."
I wouldn't say there's a lack of "health literacy" regarding decisions to participate, but more lack of credible information and TRUST, which is what Lipset is talking about in the last two sentences quoted above.
As Lipset admits later on in the interview with Pharmalot:
"In a world where we’ve been telling people not to trust (web) sites online and then to ask them to do everything online is still a challenge. A very important takeaway is that online is great, but make sure these folks know they’re not alone and have a sense of contact that they need… The twist here was to go from awareness to randomized participant entirely online, and this is where ensuring some human contact as well as an optimized online process have proven extremely important."
Is this a case of the "dead rat" coming home to roost? See "Was a Rat Harmed in the Filming of This Pfizer Commercial?" read more..