"Antibiotics May Relieve Chronic Lower Back Pain Cases
As many as four in 10 cases of chronic lower back pain are probably caused by bacteria, and treatment with antibiotics may cure them, a study showed . . ."
From March 18 Bloomberg article.
“Parents' worries raise hurdles for Merck, GSK HPV shots
Merck and GSK have some persuading to do. A growing share of U.S. parents say they won't vaccinate their daughters against human papillomavirus, which causes cervical cancer. And that leaves Merck's Gardasil and GSK's Cervarix with a shrinking market.
According to a survey released in the journal Pediatrics, some 40% of U.S. parents were against HPV vaccination in 2008. By 2012, the share of parents who wouldn't use the vaccine grew to 44%. "That's the opposite direction that rate should be going," Mayo Clinic pediatrician and researcher Robert Jacobson said in a statement.
About 1 in 6 parents worry that the vaccines aren't safe, Bloomberg notes. That's despite studies that have shown HPV shots aren't linked to serious side effects--and do protect against cancer.
Some media reports seem to have outweighed the safety data, said one researcher who wasn't involved in the Pediatrics study. "There were a lot of very sensationalized anecdotal reports of (girls) having bad reactions to the vaccine . . .”
"For GSK, advancing a malaria vaccine into Phase III in 2009 was a triumph. When now R&D chairman Moncef Slaoui joined the firm in 1988, the project had stalled. Many doubted it was even possible to make a vaccine for parasitic infections.
Fresh thinking reenergized the project and it started to rack up impressive results. In 2004 it cut the risk of infants contracting the most severe form of malaria by 57%, raising hopes a disease that kills 660,000 a year can be brought under control. Recent months have seen small setbacks, though. New data--published in the NEJM shows the effectiveness of the vaccine declines quickly.
"It was a bit surprising to see the efficacy waned so significantly over time. In the fourth year, the vaccine did not show any protection," Ally Olotu of the Wellcome Trust Research Program in Kenya told Reuters. Olotu led follow-up work into how kids 5 to 17 months old vaccinated in a Phase II trial fared over 4 years. The team is now looking into whether giving a booster shot can extend protection.
Even at current levels of protection, there are positives to be taken from the study. For every 100 children vaccinated, 65 cases of malaria were averted over a 4-year period. Malaria Vaccines Initiative director David Kaslow told the Guardian this is a major public health benefit, and warned against becoming "over-fixated on efficacy." There is also a risk of reading too much into the trial. GSK is playing down the significance of the findings, with a spokesperson saying no "definitive answers about the duration of protection" can be drawn from the small, mid-stage trial.
Phase III trials have also had mixed results, with a paper in December suggesting the vaccine is less effective in babies than infants. Further research is now needed to assess the sub-groups of kids that benefit most and the duration of protection but overall researchers are encouraged. "There is still a clear benefit to the vaccine," study author Phil Bejon said."
Exactly right DrJ. Now we know the backstory to the corruption of Dr. Robert Daum by GSK. Basically, GSK saying "since our novel vaccine adjuvant doesn't work, we won't let DVAX's novel adjuvant reach the public". Pretty awful and cowardly of GSK.
I do not believe DVAX uses the GSK adjuvant mentioned above.
That being said, I guess the point of the Reuters article was to highlight why GSK (via Daum) corrupted the AdComm panel - because GSK couldn't get their novel adjuvant to work, they had Daum transfer this fear to the completely unrelated novel DVAX adjuvant. Note that the problematic GSK adjuvant was used in a pediatric setting - the exact same idiotic and hypothetical rationale Daum partially used to justify a no vote for Heplisav safety (even though Heplisav was targeted for 18-70 years).
To be fair, a brilliantly corrupt strategy to get Daum on board to plant the seed of fear for DVAX that was experienced by GSK for their failed adjuvant. Daum can honesty say that he was worried about the Heplisav adjuvant in children (even though that was not the age groups being sought by DVAX nor even remotely related to the DVAX adjuvant).
Check out Reuters story today RE: GSK (and likely Dr.Daum's corrupted negative vote on new vaccine adjuvants.)
(Reuters) - Growing evidence of a link between GlaxoSmithKline Plc's pandemic flu vaccine and an increase in narcolepsy cases among children who received it in Europe, is giving pause to health regulators weighing approval of a similar vaccine in the United States.
Data published recently in the British Medical Journal found that children in England who received GSK's Pandemrix vaccine during the 2009-10 H1N1 swine flu pandemic had a 14-fold heightened risk of developing narcolepsy, a chronic and potentially debilitating sleep disorder that can cause hallucinations, daytime sleepiness and cataplexy, a form of muscle weakness precipitated by strong emotion.
Authors of the study - whose results echo those of similar studies in Sweden, Finland and Ireland - said the data had implications for the approval and use of future vaccines that, like Pandemrix, contain AS03, a new adjuvant, or booster, that turbo-charges the body's immune response to the vaccine...
Rebu, the following quote is absolutely wrong "At this point, generic biologics, including generic Engerix-B, are not allowed to be made." See the PPACA of 2010. This law is fairly well known - copycat biological drugs are legally permissable - whether FDA approves them (or market accepts them) is another story.
Also, Figuring out when biological drugs "come off patent protection" is a bit more complicated than traditional small molecule drugs (like Lipitor). unfortunately, there is no Orange Book equivalent for biological drugs - so knowing what patents protect what biological drug requires some deep digging.
jack, technically, any copy of the biological drug Energix would be either a (i) a "biosimilar" or an (ii) "interchangeable" biologic - the latter being more similar to a generic drug as we currently know it. Interchangeable biologics would be available to be substituted by a health care professional (e.g., pharmacist). "biosimilars" wold not - they would be treated pretty much as a new drug.
You likely know that the Patient Protection and Affordability Act was passed in 2010 allowing for such biological copycat drugs. It may be a while before any biosimilars are approved (5 years ??) - truly interchangeable biologics (a.k.a. "generic biologics") approval even further off.
Excerpts from a March 4, 2013 Pink Sheets article. Note significance of paragraph 6 and GSK’s failures with novel adjuvants. Just shocking.
Title: Vaccine Manufacturing Changes Aim To Boost Effectiveness Rate
1. “CDC and FDA officials testify about research underway to make more effective flu vaccines…”
2. “Flu vaccines have been going through a technical makeover even as manufacturers continue to struggle with fulfilling their basic promise of efficacy.”
3. “And FDA recently approved two vaccines that utilize cell-based and recombinant technology, which have the potential to speed up vaccine production over the traditional egg-based method. But manufacturers still need to boost the effectiveness of their vaccines.”
4. “At a recent congressional hearing on influenza, CDC Director Thomas Frieden noted that some progress is being made to improve vaccine manufacturing. ‘You could describe these as important and useful tweaks, but yet no breakthroughs in terms of better, longer-lasting, more effective vaccines,’ he stated at a Feb. 13 hearing of the House Energy and Commerce Committee’s Subcommittee on Oversight and Investigations.”
5. “FDA Chief Scientist Jesse Goodman also testified that the development of a more effective flu vaccine is a high priority for the agency . . .. In his written testimony, Goodman noted that the government and industry are also supporting R&D on novel adjuvants, substances added to a vaccine to boost an individual’s immune response.”
6. “In an interview of GSK’s Leonard Friedland, VP and head of North America Vaccines Clinical Development and Medical Affairs, noted that GSK has ongoing research to see if vaccines can be changed to provide more protection. Specifically, the company is continuing to look at new adjuvants to see if they can increase protection. Friedland said GSK conducted a study with a new adjuvant a few years ago in people 65 and older, and found that the vaccine with the adjuvant was not superior, Friedland said.
To those affected by corrupted FDA AdComm panels.
I think now is a great time to coin a fresh neologism pertaining to the corruption of an FDA AdComm meeting by one or more conflicted persons. It’s been going on for years and is hurting the US economy. Now is the ideal time to give it an easy to remember name.
I suggest the phrase “Daumgraded” and variants thereof (e.g., “Daumgrading”) in light of Dr. Robert Daum’s bizarre actions on the DVAX AdComm panel. Daumgrading would apply to any thinly veiled corruption at an FDA AdComm meeting that leads to an unfair negative review of an otherwise safe and effective drug application. It would obviously be analogous to an analyst “downgrading’ of a stock. Not unlike the negative connotations of Gerrymandering or the manipulative aspects of Mesmerizing.
For example, “After that bizarre AdComm meeting, biotech analysts were forced to Daumgrade the stock”.
Thanks for reading. My therapy session is now over. Cheers.
Hey dnb. Do we know who DVAX hired as a "consultant" - or if they even had a consultant? Someone clearly dropped the ball here. I'd like to avoid such consultant personnel in the future. Cheers.
Hanging well Kersh. Seems probable that all of the damage from the AdComm fabricated safety issue has passed. Kind of nice to just sit back an take slow steady gains for an inevitable approval for the limited indication. FDA wants this thing approved and the issuance of the illogical CRL has now provided cover for their #$%$.
Sentiment: Strong Buy
I encourage all followers of this message board to read Theodore Cohen's 2010 semi-fictitious book "Death by Wall Street: Rampage of the Bulls". While fiction, the parallels between the plot of his highly readable 2010 book and those of the 2012/13 DVAX Heplisav saga are disturbingly uncanny - i mean right down to the single NO vote at the AdComm meeting and mysterious grant payments to Dr. Daum by GSK. You can get a Kindle download for like $4. I knocked it out in a few hours.
Please excuse me if this book is already well-known to those of this board.
Sentiment: Strong Buy
Raven, nicely put. I also assumed that Daum's corrupted opinion would be simply acknowledged by FDA, then promptly dismissed FDA as having no factual basis. Prior to AdComm, I can only assume FDA was well aware of the faux safety concerns and chose not to even waste time concerning themselves with it - hence, no mention of it in FDA's AdComm review.
What does surprise me is DVAX's inability to get that "medium deal" by PUDUFA. I realize FDA did screw them by suggesting the larger age group, only to cower in light of Daum's bizarre logic. Funny how a pediatrician gets to make the call for adult vaccinations. Still holding long - Heplisav will be approved, just after special interests cover their butts.
Sentiment: Strong Buy
In a “complete response” letter for the novel, adjuvanted hepatitis B vaccine, FDA cites the need for more safety data in the broad population of adults for which approval was sought; however, Dynavax says the agency appears open to considering a more restricted use, such as in patients with chronic kidney disease.
Dynavax Technologies Corp. is eyeing narrower populations – including chronic kidney disease patients and individuals ages 40 years and older – as a potential route to approval for its novel, adjuvanted hepatitis B vaccine Heplisav now that FDA has issued a “complete response” letter for broad use in adults.
On Feb. 25, one day after the vaccine’s user fee date, Dynavax announced that FDA had declined to approve Heplisav (rHBsAg-1018 ISS) for adults ages 18-70 years. The “complete response” letter cited several deficiencies, most notably the need for further clinical evaluation of safety in this broad age group.
FDA also cited concerns that the vaccine’s novel adjuvant may cause rare autoimmune events, according to the company.
The 1018 ISS adjuvant is a synthetic cytosine phosphoguanine oligodeoxynucleotide that interacts with toll-like receptor 9 to increase the immune response to the vaccine’s antigen. Heplisav is designed to provide higher and earlier protection, with fewer doses, than currently licensed vaccines.
Yet, Dynavax saw a ray of sunshine in FDA’s negative regulatory action on its BLA.
“The agency indicated its willingness to continue discussions regarding a more restricted use of Heplisav,” the company said in a press release. “Dynavax plans to discuss the CRL with the FDA to identify the most expeditious path to approval for Heplisav, particularly in adults who may receive the greatest benefit.” The company said it believes the meeting with FDA will take place within six weeks.
Aside from the clinical deficiencies cited in the “complete response” letter, FDA also requested additional data from Dynavax’s process validation program and clarifying information on the manufacturing controls and facilities related to quality assurance of the commercial product. “Dynavax believes it can provide the information but the exact timeframe for its response cannot be determined until it has met with the agency,” the company said.
Dynavax’s stock was down sharply on news of the “complete response” letter, falling 32% to close at $2.01 on Feb. 25. Nevertheless, FDA’s regulatory action should not have been viewed as surprising, particularly given safety concerns raised by agency staff ahead of a November 2012 meeting of the Vaccines and Related Biological Products Advisory Committee meeting and the outcome of that meeting ("Vaccine Adjuvant Heightens Panel’s Worries About Rare Adverse Events With Heplisav" — "The Pink Sheet," Nov. 19, 2012).
Safety Data Limitations …
The Heplisav BLA was supported by two Phase III trials that evaluated the investigational vaccine against GlaxoSmithKline PLC’s nonadjuvanted hepatitis B vaccine Engerix-B.
The safety population for Dynavax’s vaccine consisted of 4,425 clinical trial subjects administered Heplisav and 1,420 who received Engerix-B. Follow-up for adverse events was 28 weeks in the two pivotal studies; for serious adverse events, follow-up was 28 weeks in one study and 52 weeks in the other.
In briefing documents released ahead of the Nov. 15 advisory committee meeting, FDA said the pre-licensure safety database for Heplisav may lack sufficient power to detect rare adverse events. The agency raised concerns about the limited prior human experience with the 1018 ISS adjuvant, the limited follow-up periods in the studies, and the fact that autoimmune diseases have a relatively low incidence in the general population ("Dynavax Hepatitis B Vaccine Could Get Comparative Post-Market Autoimmunity Assessment" — "The Pink Sheet" DAILY, Nov. 13, 2012).
Concerns about the potential for autoimmune reactions with Heplisav date back to 2008, when a participant in one of the Phase III trials developed Wegener’s granulomatosis, a rare inflammation of the blood vessels. This event led FDA to place the development program under a clinical hold in March 2008, an action that ultimately doomed Dynavax’s co-development deal with Merck & Co. Inc. ("Merck Returns Heplisav To Dynavax After FDA Rules Vaccine Too Risky For Healthy Adults" — "The Pink Sheet" DAILY, Dec. 19, 2008).
FDA lifted the clinical hold in September 2009, allowing Dynavax to resume Phase III studies that targeted adults who are less responsive to current vaccines, including those over 40 years of age, and those with chronic kidney disease (including end-stage renal disease), HIV or chronic liver disease ("FDA Lifts Clinical Hold On Dynavax's Hep B Vaccine Heplisav, Narrows Population" — "The Pink Sheet" DAILY, Sep. 10, 2009).
… Lead To Negative AdComm Recommendation
In connection with its BLA filing, Dynavax had proposed to conduct a post-marketing, open-label, prospective, 30,000-patient observational study to #$%$ the incidence of medically significant adverse events, including autoimmune disease, in individuals vaccinated with Heplisav versus those given Engerix-B. However, the majority of committee members said this proposed study was not enough to alleviate their safety concerns, and they voted 8-5, with one abstention, that the available data do not support the vaccine’s safety in individuals 18-70 years of age. The panel voted 13-1 that immunogenicity data supported the product’s efficacy ("FDA Panel Considers Dynavax’s Heplisav Safety Database Insufficient" — "The Pink Sheet" DAILY, Nov. 15, 2012).
Committee members believed a larger safety database was needed, particularly for a vaccine with a novel adjuvant. However, they also conceded that a larger dataset still may not shed much light on the occurrence of very rare autoimmune events. Some panelists therefore suggested the vaccine should be considered for approval in high-risk patients who would derive the greatest benefit.
New Populations Targeted
During a Feb. 25 conference call, Dynavax CEO Dino Dina said the company will discuss with FDA whether approval in a more focused population – such as chronic kidney disease patients, adults over age 40 and other groups who do not respond well to currently available hepatitis B vaccines – may be achievable without additional clinical studies.
Dynavax has conducted studies in CKD patients, but not all of that data was available when the BLA was submitted. The company has said that FDA suggested Dynavax submit the application for a broad indication in all adults, with plans to submit the CKD data as a supplemental BLA after the vaccine’s approval.
In March 2012, Dynavax announced final data from a Phase III trial in more than 500 CKD patients who received either three doses of Heplisav or eight total doses of Engerix-B. The company reported that the study demonstrated significantly superior seroprotection with Heplisav compared with Engerix-B at seven months.
At that time, Dynavax said it planned to file an sBLA for an indication and a three-dose primary vaccination regimen in CKD patients following approval of the original BLA, which sought approval for a two-dose vaccination series. During the conference call, Dina said that since the BLA for the general population was not approved, the company will need to talk with FDA about how best to submit the CKD data, whether as part of the existing BLA or in a separate application.
The company also has published early Phase III data suggesting Heplisav provides superior and more durable seroprotection earlier than Engerix-B in adults 40-70 years of age.
Heplisav is undergoing review by the European Medicines Agency, and the company is hoping for approval in early 2014.
Sentiment: Strong Buy
Wish I could attend to ask about TLR9 safety.
16th Annual Conference on Vaccine Research
April 22-24, 2013
Hyatt Regency Inner Harbor Hotel
300 Light Street
Baltimore, MD 21202
Annual Conference on Vaccine Research
The conference provides high-quality, current reports of scientific progress featured in both invited presentations and submitted oral abstracts and posters. By drawing upon an international audience of scientists and researchers, healthcare professionals and trainees, veterinarians, vaccine manufacturers, and public health officials, the conference organizers aim to encourage the exchange of ideas across a broad range of disciplines. The opening Keynote Presentation features Dr. D.A. Henderson discussing Eradication of Disease through Vaccination, and symposium include: Malaria Vaccines-Current and Future, and Prospects for New Tuberculosis Vaccines.
Sentiment: Strong Buy
CKD and 65+ age group is the perfect way to get this vaccine on the market and do an end-around the trumped up non-existent safety issues. Think positively... maybe by hanging on a little longer, one can avoid short term capital gains.
Why Heplisav has: (i) a bright short-term future in the CKD / 65 and older at-risk population and (ii) even a brighter extended-term future in diabetes, obesity, and high cholesterol . . . and liver cancer of course.
CKD Stats (from NIH):
1. The incidence of CKD is increasing most rapidly in people ages 65 and older.
2. The incidence of recognized CKD in people ages 65 and older more than doubled between 2000 and 2008.
3. The prevalence of CKD is growing most rapidly in people ages 60 and older.
4. Between the 1988–1994 National Health and Nutrition Examination Survey (NHANES) study and the 2003–2006 NHANES study, the prevalence of CKD in people ages 60 and older jumped from 18.8 to 24.5 percent.
5. Adults with diabetes or hypertension are at an increased risk of developing CKD. Other risk factors for developing CKD include CVD, obesity, elevated cholesterol, and a family history of CKD.
Sentiment: Strong Buy