Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
RVX-208 - I agree that judging the efficacy of RVX-208 based on the FOS claim of 26% reduction in CVD events based on an increase of 1 mg/dl of apoa1 is foolish. It's really not relevant IMO.
However previous trials have demonstrated that reducing percent atheroma volume (PAV) or even slowing plaque progression has resulted in a reduction of CVD events.
Below is my case for RVX...
In the ongoing 6 month ASSURE trial, the primary endpoint of RVX-208 is a .6% reduction of PAV.
In the 24 month ASTEROID trial, high dose Rosuvastatin (Crestor) has shown the highest PAV regression with .79% PAV reduction.
“For the primary efficacy parameter of PAV, the mean (SD) decrease was -0.98% (3.15%) and the median was -0.79% (97.5% CI, -1.21% to -0.53%) (P<.001 compared with baseline). “
http://jama.jamanetwork.com/article.aspx?articleid=202629
Previous studies show .5% reduction in PAV translates to reduction in clinical events...
“the use of IVUS to detect a 0.5% to 0.6% difference between baseline and subsequent PAV is expected to translate into a clinically meaningful outcome. This expectation is supported by results of many previous studies, i.e. Esperion, ASTEROID, PERISCOPE (1, 6, 5).”
http://www.resverlogix.com/upload/media_element/97/01/white_paper_rvx-208_and_atheroma_regression_as_of_aug_25_2009.pdf
Slowing plaque progression has also shown to lower CVD events...
“The second key observation is that therapies which slow atheromatous plaque progression as detected by IVUS translate into a reduction in clinical events. Three months following report of the REVERSAL study (29), the results of the PROVE-IT study (28) also confirmed the superiority of highdose atorvastatin compared with pravastatin on both disease progression and cardiovascular events see Figure 4, right panel. Similar data was demonstrated in the CAMELOT study (39) that had an imaging component embedded within the larger clinical trial. Data from this aspect of CAMELOT showed that amlodipine resulted in the slowest plaque progression rate was associated with the lowest event rate.”
http://www.resverlogix.com/upload/media_element/97/01/white_paper_rvx-208_and_atheroma_regression_as_of_aug_25_2009.pdf
“Theoretically, interventions that slow the progression of atherosclerotic disease should also improve clinical outcomes. Previous studies using coronary angiography and carotid ultrasound have established a strong relationship between the extent of disease, its rate of progression, and subsequent cardiovascular morbidity and mortality (6- 9). These findings have prompted regulatory authorities to permit labeling of therapies on the basis of their effects on atherosclerosis progression.
We also endeavored to explore the relationship between serial changes in atheroma burden and cardiovascular events. The relationship between the rate of disease progression and clinical outcome is considerably more complicated. The present study and prior analyses (24) have convincingly demonstrated that the rate of progression measured by IVUS is strongly influenced by the extent of baseline atheroma volume. In particular, the greatest degree of disease progression was observed in those subjects with the least amount of plaque at baseline. Accordingly, simple relationships do not accurately describe the relationship between change in atheroma volume and clinical outcomes. Nonetheless, the 20% of patients with MACE had a 0.95% increase in atheroma volume during these trials, while those without events had a 0.46% increase. Thus, a 0.5% difference in progression rate identified a group with adverse clinical outcomes. Interestingly, this difference is similar in magnitude to the differences in progression rate noted for effective antiatherosclerotic therapies in several IVUS trials (10- 11,14,23). The predominance of coronary revascularization among the clinical events and the relatively low rate of myocardial infarction are likely to underscore the observation of a closer relationship between disease progression and revascularization in the present analysis.”
http://content.onlinejacc.org/article.aspx?articleid=1142850
ASSERT was 12 weeks, ASSURE is 26 weeks. ApoA-1 and HDL were increasing at the end of the 12th week...
“Data presented also showed that the ApoA-I and other HDL particles continued to be increasing at the end of the 12 week study”
http://www.resverlogix.com/media/press-release.html?id=455
Slide 13...
https://docs.google.com/viewer?url=http%3A%2F%2Fclinicaltrialresults.org%2FSlides%2FASSERT_Nicholls.ppt&docid=e6dd4bce09186150cc2b62663b7495b3&a=bi&pagenumber=13&w=1618
A subgroup of the 12 week ASSERT trial showed a much higher response at the middle dose of 200 mg...
"In the high dose, ApoA-I achieved a 5.6% increase with a statistical value of p=0.06. The overall ApoA-I biomarker showed a dose trending statistical significance of p=0.035. Data presented also showed that the ApoA-I and other HDL particles continued to be increasing at the end of the 12 week study. Both the 8.3% HDL cholesterol increase and the 21.1% large particle HDL increase were highly statistically significant, p<0.01 and p<0.001 respectively. These pronounced HDL related increases via ApoA-I production are important as they take place later in the RCT chain of events and strongly indicate plaque regression potential."
“In patients who received the newer class of statins and had baseline HDL below 45mg/dL, an important high-risk subpopulation, the middle dose of 200 mg saw the most pronounced increases of 12% in ApoA-I (p<0.002), 21% in HDL cholesterol (p<0.015) and 32% in large particle HDL (p<0.018). “
http://www.resverlogix.com/media/press-release.html?id=455
The inclusion criteria of the 26 week ASSURE trial is based on this same subgroup...
http://www.clinicaltrials.gov/ct2/show/NCT01067820?term=resverlogix&rank=4
In the 24 month Rosuvastatin ASTEROID trial, mean PAV was reduced by .79%. HDL-C increased by 14.7%.
In the 12 week ASSERT trial subgroup, HDL-C increased from a similar baseline of 44 mg/dl by 21%... almost 50% higher in about 10% of the time. Again... HDL-C and ApoA 1 levels were rising at the end of 12 weeks... ASSURE is 26 weeks.
http://jama.jamanetwork.com/article.aspx?articleid=202629
S&P report...
http://goo.gl/yH8XJ
259M shares as of Spt 2012 = $10M market cap.
http://www.mymetics.com/investor/filings
Special Protocol Assessments: The Case Studies
Add "disruptive" and "game changer"
Companion Diagnostics for Cancer Drugs Advancing Personalized Medicine
By Catherine Arnst
The medical world took little notice earlier this month when Qiagen (NASDAQ: QGEN), a German maker of diagnostics equipment, asked the Food & Drug Administration to approve its test for a certain gene mutation associated with lung cancer. The mutation, involving the epidermal growth factor receptor (EGFR) found on the surface of cells, plays an important role in the rapid spread of tumor cells and is found in about 10 percent to 15 percent of Caucasians and 40 percent of Asians with non-small cell lung cancer.
This may all sound pretty esoteric, but Qiagen’s filing is in the vanguard of a major change in the way cancer drugs are being developed—and a critical step towards the long-awaited era of personalized medicine. Qiagen’s FDA application was made in tandem with a filing by Boehringer Ingelheim, another German company with a large U.S. operation in Ridgefield, CT, for its lung cancer drug afatinib, which targets the EGFR mutation. Indeed, the test and drug were developed in tandem, and Qiagen and Boehringer want the FDA to approve them both simultaneously.
The tests in these sorts of pairings are called companion diagnostics, and they are meant to determine if a patient should receive a particular drug, or how much of the drug should be administered. A number of diagnostic and pharma companies with a presence in the Northeast are, like Qiagen and Boehringer, forging partnerships to develop drugs and companion diagnostics simultaneously—more on this below. Qiagen, whose U.S. headquarters are in Gaithersburg, MD, has more than 15 projects underway to co–develop companion diagnostics, many of them with some of the biggest pharma companies, such as New York-based Pfizer (NYSE: PFE).
Such tests aren’t new, certainly. Roche’s Herceptin, prescribed for women with HER2-positive breast cancer, was the first cancer drug
to be approved with a companion test, back in 1998. Progress has been slow since, however. According to a study published in July 2011 by Joshua Cohen at the Tufts Center for the Study of Drug Development in Boston, less than one percent of drugs available in the U.S.—most of them cancer drugs—have a companion diagnostic.
Part of the problem, Cohen determined, is that insurers are reluctant to reimburse for the tests because there is not enough proof to justify the cost that using them improves the efficacy of the drugs. But most of the existing tests were developed after the drugs they’re paired with were already on the market. Stephen Little, Qiagen’s vice president of personalized healthcare, told me in an interview that co-developing a test with a drug is a different story. “Once the FDA approves the drug and the test in tandem, based on clinical evidence, reimbursement is pretty straightforward,” he said.
The FDA has made it clear in numerous forums that it is keen to issue such joint approvals. In the summer of 2011 the agency issued draft guidelines for the development and regulatory approval of companion diagnostics in order to set up a clear pathway and speed such co-developments along.
Cancer is particularly suited to test/drug pairing, thanks to the discovery of more and more genetic mutations associated with cancer. The shift in oncology to targeted therapies over the last decade has made the search for diagnostics that can identify patients with those targets an obvious scientific, and business, strategy. “A successful diagnostic will clearly enhance the benefit to risk ratio,” said Andrew Dorner, vice president of translational medicine for Millennium: The Takeda Oncology Company in Cambridge, MA. “I think the general strategy for pharmaceutical development now is to understand how we can select those patients most likely to respond to a drug.” That both speeds up clinical trial enrollment and makes it easier to prescribe the drug to the correct patients if and when it’s approved, he said.
In fact, a companion diagnostic developed by Qiagen for AstraZeneca’s (NYSE:AZN) lung cancer drug gefitinib (Iressa) basically saved the drug. Gefitinib won FDA approval in 2003 for non-small cell lung cancer but its use was soon severely restricted
after it turned out the drug did not help patients live longer than older therapies. A few years later AstraZeneca partnered with Qiagen to develop a test that would identify those patients with the specific mutation that the drug targets, and in 2009 the two companies won European approval for both the test and the drug, breathing new life into gefitinib.
The FDA sent a clear signal that it will look kindly on joint cancer drugs/test filings in August 2011, when it approved two such pairings in rapid succession: Roche’s vemurafenib (Zelbarof) for metastatic melanoma along with a test also developed by Roche; and crizotonib (Xalkori), made by New York-based Pfizer (NYSE: [[ticker: PFE]]) for non-small cell lung cancer, with a test by Abbott Laboratories (NYSE: [[Ticker:ABT]]) of Abbott Park, IL. Both the Roche and Pfizer drugs target mutations found only in a very small percentage of patients, and both companies said at the time that the parallel development of a companion diagnostic enabled them to speed up the timeline for their drugs.
Since then, deals between test makers and oncology drug companies have only accelerated.
• Syndax Pharmaceuticals of Waltham, MA, teamed up with Ventana Medical Systems, a Roche subsidiary, in January 2012 to develop a test to identify lung cancer patients most likely to respond to its experimental drug entinostat, for non-small cell lung cancer.
• In April 2012 Seattle Genetics (NASDAQ: SGEN), based in Bothell, WA, and Millennium announced a partnership withVentana to develop a companion diagnostic for brentuximab vedotin (Adcetris), a non-Hodgkins lymphoma drug approved in August 2011. Their goal is to be able to identify not only non-Hodgkins patients most likely to respond to the drug, but to identify other cancers with the same mutations.
• In October Qiagen inked a deal with Germany’s Bayer to develop diagnostics in conjunction with targeted therapies for solid tumors, starting at the very earliest stage of drug discovery. Qiagen already had a similar deal in place with Pfizer.
• This month Japan’s Astellas Pharma and Roche filed with the FDA for joint approval for an expanded use of Astellas’ erlotinib (Tarceva) in lung cancer using Roche’s companion diagnostic.
The dual development approach doesn’t always work, however. In September, MolecularMD of Portland, OR, pulled its FDA application for a companion diagnostic for Cambridge-based Ariad Pharmaceutical’s ponatinib, then also under review for treatment of two rare types of leukemia. The FDA had informed MolecularMD that its test didn’t qualify as a companion diagnostic because it didn’t “provide information that is essential for the safe and effective use” of the drug. The withdrawal didn’t harm the application from Ariad (NADSAQ: ARIA), however—ponatinib (Iclusig) was approved in December, three months ahead of schedule.
The Biotech Industry Organization (BIO) raised concerns about the FDA’s emphasis on parallel development of diagnostics and drugs in its comments to the draft guidance, worrying that the FDA guidelines don’t take into consideration the real-world stumbling blocks often in the way of such joint efforts. The trade association pointed out that it is not uncommon for development of the test and the companion drug to fall out of sync, or for a pertinent biomarker to not even be discovered until late in the development process, thus leaving the test’s development to late in the game.
William Goeckeler, head of oncology medical affairs at Boehringer, told me that certainly not all drugs, or all tumors, are amenable to companion diagnostics. The biology can be very tricky, and many tumors use multiple genetic pathways to grow and multiply. Nevertheless, he thinks in the future almost all cancer clinical trials will have a biomarker component that lends itself to a companion diagnostic. In fact, Boehringer started a major campaign in April, called “Let’s Test,” to educate oncologists and other health professionals about the value of testing their patients for biomarkers associated with their cancers.
“This is a very important area for us. We are really working on trying to incorporate diagnostics for biomarkers into the drugs we develop,” Goeckeler said. “This is transitioning into a commercial reality.”
http://globalregulatoryscience.com/2013/02/21/companion-diagnostics-for-cancer-drugs-advancing-personalized-medicine/
Great news! But is it enough to attract a partner?
Weekly Biotech/Pharma Volatility Tracker -- NVGN and CHTP soar on positive news
NVGN shares have quadrupled over the course of the week following positive news for its anti-cancer drug CS-6. CHTP also surged over 100 on an FDA reversal of opinion regarding one of the company's Phase 3 trials. Check out the "Recent Events" section and Anticipated Movers list below for more information on these catalysts and to identify others in the coming weeks. Finally, be sure to use our Calendar of Upcoming Events to prepare for the many catalysts scheduled for 2013.
Recent Events
Novogen (NVGN) is this week's biggest gainer, rising from Friday's closing price of $2.09 to today's highs of $10.49. The catalyst for this monster move was an update on the company's lead experimental anti-cancer drug, CS-6. In a press release the company said CS-6, "has proved highly effective at stopping the growth of cancer stem cells, eventually causing them to die." This is important because, "Cancer stem cells have been identified in a range of cancers including gut, skin, ovarian and brain cancers and leukaemia. Cancer stem cells are almost completely resistant to radiotherapy and standard anti-cancer drugs. Although representing less than about 1% of all cells present in these cancers, they are thought to be the cause of cancer relapse following radiotherapy and chemotherapy where the bulk of the tumour is replaced with new highly- resistant cells derived from the cancer stem cells."
Herbalife (HLF) has had another volatile week as the Bill Ackman versus Carl Icahn saga continues on. Shares surged nearly 30% in premarket trading last Friday after Icahn disclosed ownership of a 12.98% stake in the company. The stock was unable to hold onto gains, however, and returned to pre-announcement levels by the close. The company reported fourth quarter earnings slightly above expectations on Tuesday afternoon. It was also revealed that the company requested a meeting with the staff of the SEC's Division of Enforcement.
Chelsea Therapeutics (CHTP) shares surged 150% on Wednesday after the company announced it received written guidance from the Director of the Office of New Drugs at the FDA stating that Study 306B has the potential to serve as the basis for a resubmission of a Northera (droxidopa) New Drug Application (NDA) for the treatment of symptomatic neurogenic orthostatic hypotension. The guidance is in response to a formal appeal by Chelsea. The announcement comes as a surprise given that it is a direct reversal of the FDA's previous stance that Study 306B would be unlikely to provide sufficient confirmatory evidence required for approval. Chelsea plans to file a resubmission of the Northera NDA in the late second quarter of 2013. If accepted, the Company's application will be subject to a 6-month review period.
Cornerstone Therapeutics (CRTX) spiked higher yesterday after revealing it received a take-private proposal from Chiesi Farmaceutici SpA at $6.40-6.70 per share. Chiesi already owns approximately 60% of the outstanding shares of the company's common stock.
Exact Sciences (EXAS) is down nearly 10% over the last two sessions. The company reported a fourth quarter loss of $0.22, four cents worse than the Capital IQ Consensus Estimate for a loss of $0.18. Revenues also fell slightly year over year to $1.04 million. It was also announced that the company submitted to the FDA the second module of its premarket approval application for its stool DNA colorectal cancer screening test. Maxim noted that the submission was slightly delayed and reiterated a negative outlook. The Benchmark Company has taken an opposite stance, stating that they believe the test has a high likelihood of obtaining approval and could capture a piece of an estimated $8 billion market. Exact Sciences was listed on our Anticipated Movers table last week.
CombiMatrix (CBMX) is up over 100% today on heavy volume. There does not appear to be any news on the stock aside from a blog article stating that shares will, "double by the end of the month." The author of the article disclosed holding a long position. Shares made a similar type of run in early December following results from a pair of studies on chromosomal microarray analysis, CombiMatrix's "specialty."
Repros Therapeutics (RPRX) is up over 30% this morning. The FDA has told Repros to proceed with the analysis of ZA-301 as previously planned, and that data should be evaluated both with and without patients from the high enrolling site where the patients' baseline characteristics appeared differently from other sites in the study. Additionally, the FDA accepted Repros' plan regarding study ZA-302 to enroll additional patients. They also noted that Repros should revise the statistical analysis plan and sample size to reflect increased enrollment. Study ZA-302 will also be analyzed with and without patients from the high enrolling site where the patients' baseline characteristics appeared different from other sites in the study.
Gentium (GENT) shares came under pressure this morning, with shares trading down as much as 30%. The company announced based on preliminary feedback from the European Medicines Agency's Committee for Medicinal Products for Human Use, it expects an opinion recommending against approval of the Marketing Authorization Application for Defibrotide to treat and prevent hepatic veno-occlusive disease in adults and children undergoing hematopoietic stem cell transplantation therapy. While not a final decision, the Company considers it unlikely that this position will change before the formal vote is undertaken next month.
Notable gainers on earnings include Bruker (BRKR) and Allscripts Healthcare Solution (MDRX). There was one notable decliner: Bacterin International (BONE).
Lastly, Oncolytics Biotech (ONCY) shares have fallen approximately 15% after the pricing of a public offering of 8 million common shares at $4.00 per share.
Trading Ideas, Anticipated Movers & Upcoming Events
Anticipated Movers:
Volatility remains high in several stocks on our Anticipated Movers list, most notably DVAX and AFFY. New additions to the list include MELA, SRPT, and ATRS. Volatility moderated or near term catalysts have been eliminated in BCRX, ALXA, and EXAS, which have been removed from the list.
Looking at the bigger list, implied volatility is elevated in a large number of biotech/pharmacy stocks, including the following: DVAX, MELA, SRPT, ATRS, SQNM, AFFY, and THRX. These elevated volatility levels are indicative of expectations for greater volatility in these stocks in the future.
Read more: http://www.briefing.com/InPlayEq/Commentary/SpecialReports.htm##ixzz2LZ76aK1G
Under Creative Commons License: Attribution
Follow us: @Briefingcom on Twitter | Briefingcom on Facebook
MDXG just released a new investor presentation with some new updates. Multiple health plans are currently reimbursing Epifix + 2 VA studies demonstrated for wounds that showed no improvement after 4 wks with SOC Epifix healed 50% faster at 42% less cost with avg 2.4 applications. Overall savings to facility: $9 million over two years...
http://www.mimedx.com/media/pdf/MDXG%20Investor%20presentation%20020213.pdf
New Investor presentation - Feb 2013
http://www.mimedx.com/media/pdf/MDXG%20Investor%20presentation%20020213.pdf
4Q 2012 top 100 drug sales...
http://www.drugs.com/stats/top100/sales
Sophiris rolls out $75M IPO to finance PhIII enlarged prostate drug
S-1 filing...
http://www.sec.gov/Archives/edgar/data/1563855/000119312513062875/d443122ds1.htm
A New Old Diabetes and Obesity Drug Candidate
Posted by Derek
$2.44 is the 50% fib retracement... 2.24 is 61.8%. That would be a good entry point IMO.. 61.8% is common reversal point.
Miller said 1% reduction would be homerun
Trial sans Error: How Pharma-Funded Research Cherry-Picks Positive Results [Excerpt]
NVGN Novogen up another 25% today, continued strength on CS-6 press release. (8.05 +1.58)
Shares of Novogen are trading higher by over 25% this morning. The move appears to be continued strength on positive news for the company's lead experimental anti-cancer drug, CS-6. To recap: in a press release the company said, CS-6, "has proved highly effective at stopping the growth of cancer stem cells, eventually causing them to die." This is important because, "Cancer stem cells have been identified in a range of cancers including gut, skin, ovarian and brain cancers and leukaemia. Cancer stem cells are almost completely resistant to radiotherapy and standard anti-cancer drugs. Although representing less than about 1% of all cells present in these cancers, they are thought to be the cause of cancer relapse following radiotherapy and chemotherapy where the bulk of the tumour is replaced with new highly- resistant cells derived from the cancer stem cells."
Briefing note: as of Jan 31, 2013 short interest in the stock was less than 20k shares versus over 4 million shares outstanding.
Read more: http://www.briefing.com/InPlayEq/InPlay/InPlayDual.htm#ixzz2LT0vmq9R
Under Creative Commons License: Attribution
Follow us: @Briefingcom on Twitter | Briefingcom on Facebook
The only one worth listening to on RVXCF is David Miller of BSR...
http://investorshub.advfn.com/boards/read_person.aspx?membernum=62662
There was a spirited discussion on Resverlogix on the Biotech Values board back in Nov 2012. Starting here...
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=81605723
Then David Miller chimed in ...
Almost one-third of chemotherapy used "off-label"
By Andrew M. Seaman
NEW YORK | Tue Feb 19, 2013 4:44pm EST
(Reuters Health) - About one-third of chemotherapies are used to fight cancers that drug regulators never approved them to treat, says a new study.
Chemotherapies - drugs that kill rapidly dividing cells - are approved by the Food and Drug Administration (FDA) to fight specific cancers, but there's nothing stopping doctors from prescribing the drugs "off-label" to treat other types of tumors.
Some researchers have questioned whether doctors were prescribing the expensive and toxic drugs outside of their intended use, according to the study's researchers, led by Rena Conti, an assistant professor of health policy and economics at the University of Chicago.
"The main criticism of off-label prescribing has been the concern that it jeopardizes patient safety because the full risk-benefit ratio is often not completely understood," wrote the University of Toronto's Dr. Monika Krzyzanowska, who published an editorial accompanying the study in the Journal of Clinical Oncology on Tuesday.
But that doesn't mean the billions of dollars spent on off-label chemotherapies are wasted, according to Conti.
"We don't know what the outcomes are. We can't make a judgment of whether the off-label use we document… is appropriate or inappropriate," said Conti.
For the new study, the researchers used a national prescription database from U.S. cancer doctors to estimate how the most common intravenous or injected chemotherapies were used in 2010.
They found ten chemotherapies that were still protected from competition by patents. They ranged from almost 500,000 doses of Genentech's Avastin or bevacizumab - approved to treat brain, colorectal, lung and kidney cancers - to about 53,000 doses of Celegene's Vidaza or azacitidine - used to treat certain blood disorders.
Overall, about 70 percent of the doses of the ten chemotherapies were used "on-label," which means the doses were used in line with FDA approval. The other 30 percent was used to treat cancers the drug regulators never approved.
The researchers also looked at whether the off-label use of chemotherapies was supported by the National Comprehensive Care Network (NCCN), a group that publishes its own guidelines on cancer care.
They found that 14 percent of chemotherapies were prescribed off label but were supported by the NCCN's expert opinion, and 10 percent were prescribed without NCCN or FDA support.
Conti told Reuters Health that doctors follow guidelines from expert organizations when there is not enough data for the FDA to make a decision, such as when rare diseases make it too difficult to conduct a clinical trial.
Conti and her colleagues point out, however, that some researchers have criticized NCCN recommendations, because of possible delays in guidelines based on the latest data, and possible conflicts of interests.
The total cost of chemotherapies for 2010 was $12 billion. Of that, $4.5 billion went toward off-label chemotherapies - $2.5 billion for non-NCCN supported uses.
‘A LITTLE TROUBLING'
"To me it's a little troubling that so many drugs are given in areas where there is not a lot of data to back it up," said Dr. Nancy Keating, a cancer researcher who was not involved with the new study.
"The tricky thing is patients with cancer and their doctors are looking for anything with a benefit. So I think they're sometimes willing to try things where there isn't as much data as you would like," said Keating, from Boston's Harvard Medical School and Brigham and Women's Hospital.
But Conti said they can't tell from their data whether patients prescribed on-label chemotherapy did better than patients receiving off-label chemotherapy.
"What our study basically does is highlight this proportion of use that is off-label and endorsed by expert opinion, or off-label and not endorsed by expert opinion," Conti said.
She added that their study shows chemotherapy use is driven by FDA approval and expert opinion. The other chunk that's prescribed without expert or FDA backing may be in response to a lack of available treatments, she said.
ABBV-ABT-199 Tumor Lysis Syndrome - what is it and why is it important in cancer research?
Sally Church...
http://www.biotechinvestorsnetwork.com/#!feature-2/c1bc6
Right you are sir... from a different source though. Sorry about that.
AbbVie CEO Says Humira Will Blunt $1B Hit To Lipid Franchise
22 mins ago by editor 0
By Bruce Japsen
AbbVie Chairman and CEO Rick Gonzalez remains bullish on the company’s biologic Humira to treat myriad autoimmune diseases and drive sales for “many years to come.”
The former proprietary drug business ofAbbott Laboratories (ABT), now split off into AbbVie (ABBV), expects to continue to benefit from the robust growth of its Humira biologic for myriad autoimmune diseases.
For better or worse, the sure bet for AbbVie remains Humira with the company’s lipid franchise, which includes the cholesterol treatments Niaspan and Tricor, losing market share with generics entering the market. AbbVie said such treatments for the prevention of heart disease will lose more than $1.2 billion in sales this year.
But AbbVie’s management team said its new company is still off to a good start thanks to Humira, which is used as a treatment for everything from rheumatoid arthritis and psoriasis to Crohn’s disease. Humira sales jumped 23 percent to $2.7 billion in the fourth quarter.
“Humira will continue to drive cash flow growth for many years to come,” AbbVie chairman and chief executive officer Rick Gonzalez told Wall Streetanalysts and investors this morning on an hour-long conference call – the company’s first with analysts and investors following its split off from Abbott. “There’s not a better asset in the pharmaceutical industry than Humira.”
For the first time, AbbVie issued full-year 2013 adjusted earnings-per-share guidance of $3.03 to $3.13, which was in line with analysts’ estimates of $3.08. Total sales, meanwhile, are projected to be “somewhat above” $18 billion, which analysts say would put them slightly ahead of last year’s annual revenue.
Many Wall Street analysts and investors worry about Humira with one observer on this morning’s call calling the drug both a “blessing and a curse.” Humira, which faces its first patent expirations in 2016, accounts for half of AbbVie’s revenue and 70 percent of company profits.
Meanwhile, Humira is already in a competitive market against similar biologics made by Amgen(AMGN) and Johnson & Johnson (JNJ) as well as the new rheumatoid arthritis drug Xeljanz, which is sold by Pfizer (PFE).
Gonzalez said Humira is still unknown in many parts of the word and will benefit from “further geographic penetration” with the company forecasting low double-digit percentage growth this year. Humira is also poised to launch several new indications, including four in late-stage development such as pediatric Crohn’s disease.
High-stakes cholesterol study could lift Merck cloud
By Ransdell Pierson and Bill Berkrot
NEW YORK | Fri Feb 15, 2013 4:03pm EST
(Reuters) - Favorable results from a huge heart study could help redeem investors' faith in Merck & Co and its two biggest cholesterol drugs, Vytorin and Zetia, and potentially add billions of dollars in annual revenue.
Investors have soured on the No. 2 U.S. drugmaker since late December, following setbacks to a closely watched experimental drug for osteoporosis and a newer cholesterol medicine.
Those concerns come on top of investor anxiety over the outcome of the study of 18,000 heart patients called IMPROVE-IT that has contributed to Merck's shares lagging rival large drugmakers by about 10 percentage points in that short period.
An independent monitoring board is expected to complete an interim analysis of the study in March, and decide whether it should continue as planned until September 2014.
Sales of Vytorin and Zetia have fallen since 2008 because of concerns about their effectiveness and safety.
"If the data are extremely good, and statistically significant, that would be a big win for Merck, and there's no reason combined sales of Vytorin and Zetia couldn't climb by billions" of dollars, said Morningstar analyst Damien Conover.
The IMPROVE-IT study involves patients with already well-controlled cholesterol who had heart attacks or the kind of chest pain that can precede heart attacks. It looks to determine if Merck's $1.75 billion-a-year Vytorin pill can significantly reduce heart attacks, strokes and heart-related deaths compared with the company's older, generically-available Zocor.
Vytorin, approved in 2004, combines Zocor with Zetia, so the study is a measure of the clinical benefit of adding Zetia, which lowers bad LDL cholesterol by blocking the liver's production of the blood fat.
Zetia, which is also sold separately and has annual sales of almost $2.6 billion, is prescribed by doctors as a standalone treatment or to add to the cholesterol-lowering power of statins, such as Zocor or Lipitor.
The monitoring board, based upon data only it has the right to see, could order an early halt to the trial if it believes the data already show Vytorin is more heart protective than Zocor, if it deems Vytorin to be clearly no better than Zocor or if safety problems arise with Vytorin.
Blinded studies have independent safety monitoring boards to make sure drugs are not harmful, or are so effective that it would be unethical not to offer the meds to the placebo group.
"If the trial stops because it shows efficacy, Merck shares could rise a great deal - 10 or 15 percent, or even more," as the overhang on Merck shares is lifted, said Barclays Capital analyst Tony Butler.
GUARDED OPTIMISM
The most likely scenario is that the monitoring board will take no action, and allow the trial to continue to its planned 2014 conclusion, analysts say.
Butler, however, estimated there was a 40 percent chance that the board would determine Vytorin is superior to Zocor and order the trial halted. "There's an extraordinarily small probability, maybe 5 or 10 percent, that the trial stops due to some kind of harm," Butler added.
Morningstar's Conover said he is guardedly optimistic about positive results from IMPROVE-IT, either next month, or when the trial runs its planned full course.
"There's a cloudy outlook on Vytorin, but we feel the trial will show a trend towards efficacy," meaning better results than Zocor that might not reach statistical significance, he said.
But Merck shares could fall 10 percent or more if Vytorin fails to beat Zocor in preventing cardiovascular events, and demand for Vytorin and Zetia would wilt, analysts said.
"Global sales of Zetia and Vytorin could decline by 50 to 70 percent" in that event, according to Leerink Swann analyst Seamus Fernandez, and take Merck shares sharply lower.
Fernandez said he expects Vytorin to trump Zocor in the study, although he estimated the boost in combined Vytorin and Zetia sales would be only $500 million to $1 billion in 2016.
The prospects of rejuvenated sales of the cholesterol drugs could bolster faith in Merck that flagged after it scrapped plans to seek U.S. approval for a pill called Tredaptive used to increase "good" HDL cholesterol, and said it would delay seeking approval of an osteoporosis drug called odanacatib, prompting safety concerns for a medicine that some analysts had hoped would become a $2 billion-a-year brand.
Combined Vytorin and Zetia sales had soared to about $5 billion, until January 2008, when Vytorin proved no better at preventing plaque in neck arteries than Zocor in another large trial called ENHANCE. It involved high-risk patients with an inherited form of heart disease.
Merck on Thursday agreed to pay $688 million to settle two U.S. class-action lawsuits by shareholders who alleged the company knew more than a year in advance that the trial was a failure, but withheld that information from investors. Merck, in agreeing to the settlement, denied any wrongdoing.
Safety concerns over Zetia also arose in 2008, when another trial called SEAS appeared to suggest a link to higher rates of cancer deaths, although that was later disproved to the satisfaction of most doctors. But a clean safety result from IMPROVE-IT can only help to reassure doubters.
(Reporting By Ransdell Pierson and Bill Berkrot in New York; Editing by Jilian Mincer and Nick Zieminski)
Biotech billionaire Soon-Shiong unveils ‘convergence’ cancer drug startup
By Ryan McBride
The biotech field is covered with startup efforts with cancer drugs, but when Dr. Patrick Soon-Shiong announces one the business world stops and listens. The inventor of the blockbuster anti-cancer hopeful Abraxane has revealed plans for a new company that marries diagnostics and supercomputing with personalized drug development.
As Bloomberg reported, Soon-Shiong has already amassed a fortune of more than $7 billion from the sale of two previous pharma groups Abraxis and APP, showing no signs of letting up as he pursues new interests such as his stake in the NBA’s LA Lakers, entertainment and, as before, biotech/healthcare. Like in sports and entertainment, he told the news service, cancer care is undergoing a convergence involving multiple technologies. And he aims to improve cancer treatment with a network model for sharing data on tumor genes and concocting the right combos of cancer drugs for specific patients to beat their disease.
NantOmics, Soon-Shiong’s cancer drug startup, features a library of kinase inhibitors that could home in on multiple mutations that drive cancers regardless of where tumors reside in the body. He regained control of the kinase inhibitors from biopharma powerhouse Celgene ($CELG). Celgene sold the library to Soon-Shiong after picking it up in its $2.9 billion acquisition of Abraxis, a 2010 deal struck primarily for the reformulated chemo drug Abraxane. Not surprisingly, Soon-Shiong is funding NantOmics through his California Capital Equity group, Bloomberg reported.
Abraxane is on its way to becoming a blockbuster, with Celgene seeking later this year an additional approval of the med for treating often lethal pancreatic cancer. Yet Soon-Shiong tells Bloomberg that it’s taken 23 years for Abraxane to reach this point, and he’s aiming to speed up the process of advancing anti-cancer treatments with NantOmics, with human studies planned for this year.
NantOmics will benefit from the capabilities of its sister company, NantHealth, which uses supercomputing and a high-speed fiber-optic network to analyze data from tumor samples in under a minute and then send the info from one location to the next in mere seconds.
Soon-Schiong’s group has been processing 2,000 tumors per week and has built a network of 8,000 oncologists who form a “social network” of sorts for cancer care, he told Bloomberg TV.
His vision is to combine cloud computing, genomic analysis and targeted drug development to provide lifelong management of cancer for patients.
“We’re really going after truly creating sustainability of a disease-free state,” Soon-Shiong told Bloomberg, “creating a complete system for managing cancer patients for life.”
http://globalregulatoryscience.com/2013/02/16/biotech-billionaire-soon-shiong-unveils-convergence-cancer-drug-startup/
Bad Pharma? Maybe. But Goldacre's Selective Use of Data Is Wrong
John LaMattina, Contributor
Former president of Pfizer R&D/senior partner at PureTech Ventures
Ben Goldacre is now on a North American tour promoting his book, Bad Pharma, his expose of the pharmaceutical industry. On the book’s overleaf, he has the following quote:
“The tricks and distortions documented in these pages are beautiful, intricate, and fascinating in their details.”
Actually, the same can be said for examples that Goldacre uses to make various points in his book. Goldacre has major concerns about the need for more transparency when it comes to making data from clinical trials publicly available. In fact, he spends about one-third of Bad Pharma discussing this topic. I agree that one of the big challenges that the industry faces is the need to be more transparent about its work and I have written about this both on this blog and in Devalued & Distrusted. However, Goldacre’s cherry-picking of data to fit his arguments is inappropriate and infuriating to those who know something about the pharmaceutical industry.
Right at the outset of Bad Pharma, Goldacre tells the story of TGN1412. This is a horrific tale of six young males who, in 2006, volunteered for a phase 1 study for a novel drug, TGN1412. Phase 1 is the very first step in the study of a new drug in people. It is simply meant to test the drug, initially at very low doses, to see how well tolerated it is. TNG1412 was an antibody designed to stimulate the immune system and, in doing so, fight cancer in a whole new way. The hope for TGN1412 was to have it used to treat a rare form of leukemia.
Unfortunately, the volunteers in this phase 1 trial suffered immediate and severe side-effects. These men experienced an immunological firestorm in that the antibody caused the uncontrolled release of toxins. As a result, the volunteers suffered severe adverse events starting with rapid blood pressure lowering, then respiratory issues, kidney failure, etc. Fortunately, thanks to extraordinary efforts by excellent doctors in London Hospitals, all survived.
Goldacre’s purpose in telling this story is that he feels this episode could have been prevented in two ways. First, since this is an unprecedented experimental treatment, the drug should have not been given to six volunteers simultaneously, but rather in a staggered process. He is correct on this. Had this been done, only one volunteer would have been endangered. But his second concern is a real stretch. He believes that a study done ten years earlier by an academic researcher on a single subject could have foretold the events with TGN1412. Unfortunately, this result was never published. Goldacre uses this example to support his argument that pharma selectively publishes data and, in doing so, harms patients.
Here is what Goldacre does NOT tell you about TGN1412.
1) TGN1412 was being developed, not by a pharma company, but by TeGenero, a biotech company with 15 employees that was formed based on work done at the University of Wurzburg. TeGenero, a 15 person company, was not exactly a big pharma.
2) This was known to be a controversial area of research as people were worried that toying with the immune system could have dire consequences. Thus, experts in the field urged caution. The risks were well understood without the need of knowing about a single experiment 10 years earlier. My guess is that some experts would not agree that this isolated incident was truly relevant to the TNG1412 case.
3) TeGenero tested TNG1412 extensively in animals, particularly cynomolgus monkeys which, at the time, were believed to be a good model for the human immune system.
4) As Goldacre states later in his book when describing the drug development process, in phase 1, drugs are normally tested at one-tenth of the “no adverse effects” dose seen in animals. The “no effect” dose was 50mg/kg in monkeys. TeGenero cautiously dosed the volunteers at 0.1mg/kg, 1/500th of the “no effect” dose in cynos.
The publicity and commentary around the TGN1412 tragedy was extensive. But, rather than trash phase 1 clinical trials, the comments were surprisingly supportive.
“Research is a social good – we need better treatments for leukemia and arthritis – but there are risks…..This is a terrible tragic event but so far, I don’t see any clear ethical problems.” Dr. Ezekiel Emanuel, chief of bioethics at the NIH.
“It is certainly possible to change the way in which novel agents are tested to minimize the number of subjects who are put at risk. As long as we continue to manipulate biology in new ways, we probably cannot prevent all such events from occurring. We must do what we can to minimize risk, but the future health of the world population demands that we not let adverse events put an end to medical progress. We must treat those at risk with respect and great care, but the work must go on.” Dr. Jeffrey M. Drazen
Given this additional background, it is hard to see why Goldacre uses this example to support his arguments. Perhaps it to use sentences like: “Their fingers and toes went flushed, then brown, then black, and then began to rot and die.” That should certainly raise the ire of the general public. Unfortunately, this case is being used for sensationalism and not to advance the cause that Bad Pharma claims to espouse.
This week in biotech...
EnteroMedics (ETRM) crashed over 50% last Friday after announcing results from its randomized ReCharge Pivotal Trial of VBLOC vagal blocking therapy for the treatment of obesity. The trial demonstrated a clinically meaningful and statistically significant excess weight loss (EWL) of 24.4% for VBLOC Therapy-treated patients, with 52.5% of patients achieving at least 20% EWL. The trial met its primary safety endpoint, though it did not meet its predefined primary efficacy measures. EnteroMedics plans to move forward with a Pre-Market Approval application with the FDA in the second quarter of 2013. EnteroMedics was listed on our Anticipated Movers table last week.
Oncolytics Biotech (ONCY) shares are up over 25% since last week's report. On Friday the company announced a poster presentation covering positive preliminary results from a Phase I study examining the intravenous administration of REOLYSIN in combination with FOLFIRI in patients with metastatic colorectal cancer (REO 022). Twenty-one patients were enrolled in the study, including nine that were FOLFIRI-naive. Of the 18 patients evaluable for response there was one partial response and nine had stable disease. The combined overall progression free survival (PFS) of FOLFIRI-naive and FOLFIRI-failed patients was 7.4 months. The authors concluded that the combination of REOLYSIN and FOLFIRI was safe and well tolerated and resulted in disease control in the majority of evaluable patients, including patients that had previously progressed on Irinotecan. Oncolytics Biotech was listed on our anticipated Movers table last week.
Novo Nordisk A/S (NVO) shares fell over 10% on Monday after the company received a Complete Response Letter from the FDA for Tresiba (insulin degludec) and Ryzodeg (insulin degludec/insulin aspart). In the letter, the FDA requests additional cardiovascular data from a dedicated cardiovascular outcomes trial before the review of the New Drug Applications can be completed. The letter also states that approval cannot be granted until the violations cited in the previously announced Warning Letter, dated 12 December 2012, have been resolved. The FDA decision came as a bit of a surprise given that the Endocrinologic and Metabolic Drugs Advisory Committee voted 8-4 in favor of approving the drugs with a post-approval cardiovascular outcomes trial. This is a great example of the fact that although Advisory Committees can have significant influence, the FDA is not ultimately obligated to follow their recommendations.
Regeneron Pharmaceuticals (REGN) rose as much as 10% on Monday after the company announced it received from Sanofi (SNY) a notification under the Hart-Scott-Rodino Act that Sanofi intends to acquire common stock of Regeneron through open market purchased and direct purchases from shareholders. The notice is only triggered for purchases in excess of $500 million, indicating that Sanofi intends to make a large stake.
StemCells (STEM) gained over 20% on Tuesday following an update on patients treated with its proprietary HuCNS-SC product candidate (purified human neural stem cells) for chronic spinal cord injury. STEM reported that considerable gains in sensory function observed in two of the three patients at the six-month assessment have persisted at twelve months; the third patient remains stable. Though the trial is small, the results are encouraging.
ZIOPHARM Oncology (ZIOP) announced on Tuesday that the Phase 3 (PICASSO 3) trial of palifosfamide (ZIO-201) in first-line metastatic soft tissue sarcoma reached its target number of progression-free survival events. An Independent Data Monitoring Committee will now review the data and the company will announce topline results during the last week of March 2013. The stock is up nearly 17% on the news.
Pharmacyclics (PCYC) has seen strong gains over the past two trading sessions, rising nearly 14%. Tuesday after the close the company announced that the FDA granted Breakthrough Therapy Designation to the investigational oral agent ibrutinib monotherapy for the treatment of patients with relapsed or refractory mantle cell lymphoma and to ibrutinib monotherapy for the treatment of patients with Waldenstrom's macroglobulinemia, both of which are B-cell malignancies. The Breakthrough Therapy Designation is intended to expedite the development and review of a potential new drug for serious or life-threatening diseases where "preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development." Pharmacyclics is the first company to receive this designation since it was enacted in 2012.
iCAD (ICAD) shares have surged nearly 20% since Craig Hallum initiated the company with a Buy rating on Wednesday. iCAD is a provider of Computer-Aided Detection (CAD) technologies, advanced image analysis, workflow solutions and radiation therapies for the early identification and treatment of common cancers.
Affymax (AFFY) shares sunk as much as 33% this morning after it disclosed in a filing that Fresenius Medical paused further expansion of the OMONTYS pilot that began in late July 2012. Fresenius said, "We are now working to analyze the full set of efficacy and safety profile information and feel that the current scale of our experience with use of the drug is adequate to complete this analysis." The halt does not appear to be related to concerns or problems with the drug. Shares have rebounded sharply from the lows and the stock is now only down approximately 5%.
Hospira (HSP) also came under pressure today after the company disclosed in a filing that it received written notification from the FDA that the FDA had expanded the Symbiq import alert issued on November 8, 2012. That alert prohibited the importation of Symbiq infusion pumps into the U.S. The expansion received on February 13, 2013 prohibits the importation into the U.S. of the Plum, GemStar, and LifeCare PCA infusion pumps which are manufactured in HSP's Costa Rica facility. Assuming that the import ban on Plum, GemStar, and LifeCare PCA remains in effect throughout 2013, the Company's preliminary estimate is that the impact for this matter could be in the range of $50 to $100 million in decreased net sales and $0.10 to $0.20 reduction in U.S. GAAP earnings per share or an adjusted earnings per share impact of $0.05 to $0.15. Shares are down over 7%.
A number of stocks saw gains after reporting earnings, including Molina Healthcare (MOH), Medical Action Ind (MDCI), Albany Molecular Research (AMRI), and WellCare Group (WCG). Decliners include Misonix (MSON), and Corcept Therapeutics (CORT).
Lastly, MELA Sciences (MELA) shares have fallen over 11% since the company priced an underwritten offering of 6.1 million shares of common stock at $1.30 per share. MELA Sciences was listed on our Anticipated Movers table last week.
Trading Ideas, Anticipated Movers & Upcoming Events
Anticipated Movers:
Volatility remains high in several stocks on our Anticipated Movers list, most notably DVAX and ALXA. New additions to the list include BCRX, AFFY, THRX, and EXAS. Volatility moderated or near term catalysts have been eliminated in ETRM, IMUC, ONCY, MELA, and ARRY, which have been removed from the list.
Looking at the bigger list, implied volatility is elevated in a large number of biotech/pharmacy stocks, including the following: DVAX, BCRX, ALXA, AFFY, SQNM, THRX, and EXAS. These elevated volatility levels are indicative of expectations for greater volatility in these stocks in the future.
Read more: http://www.briefing.com/DisplayArticle/Article.aspx?ArticleId=NS20130214134117SpecialReports#ixzz2KzvUy8hY
Under Creative Commons License: Attribution
Follow us: @Briefingcom on Twitter | Briefingcom on Facebook
ABBV - ABT-199 clinical trials suspended after patient death
http://biotechstrategyblog.com/2013/02/abt-199-clinical-trials-suspended-after-patient-death.html/
Derek Lowe comments...
http://pipeline.corante.com/archives/2013/02/13/mouse_models_of_inflammation_are_basically_worthless_now_we_know.php
snip...
Bad Pharma - book review from the Boston Globe
‘Bad Pharma’ by Ben Goldacre
By Dennis Rosen | GLOBE CORRESPONDENT FEBRUARY 11, 2013
Ben Goldacre has done it again. In his previous book, “Bad Science,’’ Goldacre, a British physician and epidemiologist, made hash of much of the pseudoscience that attempts to pass itself off as a credible alternative to modern biomedicine. This time, in “Bad Pharma,’’ Goldacre turns his attention to an issue that has undermined the empirical scientific basis of biomedicine itself: the collusion of pharmaceutical companies, physicians, medical journals, governmental regulatory agencies, and medical schools in hiding and manipulating data about drug development and marketing.
Both have resulted in rendering much of what we think we know about what works and what doesn’t work in medicine not fully accurate, to put it mildly. It is heartbreaking to look at the professionals, organizations, and institutions who have been involved in this and to realize that these are precisely the ones you would have expected to rise above the opportunity to enrich themselves and to make all efforts to ensure that patients are treated with safe and effective medications.
“The book’’ Goldacre begins, “follows a simple trajectory,’’ starting with the notion that industry-sponsored studies tend to “flatter’’ the sponsor’s drug and then proceeds to look at how the positive trials are created, at the drug-discovery process, regulation, the “tricks’’ in “bad trials,’’ the marketing of drugs, and finally what can be done.
Goldacre identifies the overarching problem, first and foremost, as being one of missing data. Data from clinical trials that were never published but demonstrated that many of the medications being promoted as tomorrow’s blockbusters were no more effective — and often less so — than those already available. Data from post-marketing studies that revealed unexpected side effects from new drugs that had sickened and killed patients, but which companies delayed releasing for as long as they could. Data on the web of financial ties between industry, physicians, medical schools, and the very regulatory agencies who were supposed to be keeping the pharma-medical complex honest.
“[E]vidence in medicine is not an abstract academic preoccupation. Evidence is used to make real-world decisions, and when we are fed bad data, we make the wrong decision, inflicting unnecessary pain and suffering, and death, on people just like us,” writes Goldacre. And indeed, it is hard to read his exceedingly well-written and extensively researched account of how a lethal combination of greed and ambition, coupled with an absence of scruples, drove so many to conspire to manipulate the science from which biomedical practice derives, without sharing his outrage.
One of Goldacre’s most troubling conclusions is that repairing the damage would take much more than simply changing these unethical behaviors and standards of conduct from today onward. “[W]e need full disclosure, and I don’t say this out of some waffly notion of truth and reconciliation,” Gold-acre writes, and goes on to explain that the current practice of medicine is based, in part, upon some studies whose data were fudged, manipulated, and then presented in papers that appeared in some of the world’s most prestigious medical journals over decades. Undoing all this will require a huge review of current biomedical practice to figure out which ones need to be corrected because the data they are based upon are simply unreliable.
Goldacre is an exceptionally gifted writer: funny, sarcastic, occasionally caustic, and very thorough in his research. This is a very broad topic, which makes it difficult to condense into one volume, and yet he has succeeded in doing so in a persuasive and engaging manner. This is a morbidly fascinating and dispiriting account, yet one which deserves (and needs) to be read and acted upon without delay, if we are to be able not only to receive effective treatment when we need it, but also to believe that those who provide us that treatment actually know what they are doing.
Dennis Rosen, M.D., a pediatric lung and sleep specialist who practices in Boston, can be reached at dennis.rosen@childrens.harvard.edu.
http://bostonglobe.com/arts/books/2013/02/11/book-review-bad-pharma-how-drug-companies-mislead-doctors-and-harm-patients-ben-goldacre/VrTv8NnBhsgjhj1cWd4cVJ/story.html
Book excerpts from a more extensive review...
Drugs are tested by the people who manufacture them, in poorly designed trials, on hopelessly small numbers of weird, unrepresentative patients, and analysed using techniques that are flawed by design, in such a way that they exaggerate the benefits of treatments. Unsurprisingly, these trials tend to produce results that favour the manufacturer. When trials throw up results that companies don’t like, they are perfectly entitled to hide them from doctors and patients, so we only ever see a distorted picture of any drug’s true effects. Regulators see most of the trial data, but only from early on in a drug’s life, and even then they don’t give this data to doctors or patients, or even to other parts of government. This distorted evidence is then communicated and applied in a distorted fashion. In their forty years of practice after leaving medical school, doctors hear about what works ad hoc, from sales reps, colleagues and journals. But those colleagues can be in the pay of drug companies – often undisclosed – and the journals are, too. And so are the patient groups. And finally, academic papers, which everyone thinks of as objective, are often covertly planned and written by people who work directly for the companies, without disclosure. Sometimes whole academic journals are owned outright by one drug company. Aside from all this, for several of the most important and enduring problems in medicine, we have no idea what the best treatment is, because it’s not in anyone’s financial interest to conduct any trials at all. These are ongoing problems, and although people have claimed to fix many of them, for the most party they have failed; so all of these programs persist, but worse than ever, because now people can pretend that everything is fine after all.
Whatever our political leanings, everyone is basically a socialist when it comes to healthcare: we all feel nervous about profit taking any role in the caring professions, but that feeling has nowhere to go. Big pharma is evil: I would agree with that premise. But because people don’t understand exactly how big pharma is evil, their anger and indignation get diverted away from valid criticisms—its role in distorting data, for example, or withholding life-saving AIDS drugs from the developing world—and channelled into infantile fantasies. ‘Big pharma is evil,’ goes the line of reasoning, ‘therefore homeopathy works and the MMR vaccine causes autism.’ This is probably not helpful.
If I were to run a study, and then just remove half of my data points so that my results looked much better, well, you would laugh in my face. It would be obvious to anyone that it was research misconduct. You might even call it fraud. And yet we tolerate the results of entire clinical trials—a huge proportion of them—being withheld from doctors and patients. In medicine, we rely on summaries of evidence, we collate the results from many different trials. So withholding the results of whole trials is exactly the same insult to the data as fraudulently deleting data points from within individual studies.
Contrary to what some regulators seem to think, a drugs is not either ‘good’ and therefore on the market or ‘bad’ and off it. A regulator makes a decision about whether it’s in the interests of the population as a whole that the drug should be available for use, at all ever – even if only is some very obscure circumstance, infrequently and cautiously. The bar is set pretty low, as we shall see, and lots of drugs that are on the market (in fact, the overwhelming majority) are hardly ever used.
A doctor needs to use the same information as that available to the regulator in order to make a very different decision: is this the right drug for the patient in front of me right now? The simple fact that a drug is approved for prescription doesn’t mean it’s particularly good, or the best. In fact, there are complex decisions to be made in each clinical situation about which drug is best.
http://sciencebasedpharmacy.wordpress.com/2012/11/22/bad-pharma-a-manifesto-to-fix-the-pharmaceutical-industry/
The biology of love...
Love is, first and foremost, an emotion—but one that is, more than most emotions, rooted in our bodies. I’m not just referring to lust, though that can lead to romantic love. As love grows and deepens, it lights up some parts of our nervous systems and dims others. The importance of feel-good hormones like oxytocin and dopamine may decline over the course of a relationship—but a love that reaches maturity will bind the lovers on a neurological level.
Far from an “an ever-fixed mark,” love is a process subject to biological forces beyond our conscious control. Drawing from new research by Cal psychologist Dacher Keltner, along with Barbara Fredrickson, John Gottman, Helen Fisher, Kayt Sukel (author of Dirty Minds), and many neuroscientists, here is a list of the places where love abides in our bodies — and the role each one plays in sustaining love over time. Just in time for Valentine’s Day!
http://blogs.berkeley.edu/2013/02/08/how-love-grows-in-your-body/
Testing of Some Deadly Diseases on Mice Misleads, Report Says
By GINA KOLATA
Published: February 11, 2013
For decades, mice have been the species of choice in the study of human diseases. But now, researchers report stunning evidence that the mouse model has been totally misleading for at least three major killers — sepsis, burns and trauma. As a result, years and billions of dollars have been wasted following false leads, they say.
The study does not mean that mice are useless models for all human diseases. But, its authors said, it does raise troubling questions about diseases like the ones in the study that involve the immune system, including cancer and heart disease.
“Our article raises at least the possibility that a parallel situation may be present,” said Dr. H. Shaw Warren, a sepsis researcher at Massachusetts General Hospital and a lead author of the new study.
The paper, published Monday in the Proceedings of the National Academy of Sciences, helps explain why every one of nearly 150 drugs tested at huge expense in patients with sepsis has failed. The drug tests all were based on studies in mice. And mice, it turns out, have a disease that looks like sepsis in humans, but is very different from the human disease.
Medical experts not associated with the study said that the findings should change the course of research worldwide for a deadly and frustrating disorder. Sepsis afflicts 750,000 patients a year in the United States, kills a quarter to half of them, and costs the nation $17 billion a year. It is the leading cause of death in intensive-care units.
“This is a game changer,” said Dr. Mitchell Fink, a sepsis expert at the University of California, Los Angeles, of the new study.
“It’s amazing,” said Dr. Richard Wenzel, chairman of the department of internal medicine at Virginia Commonwealth University and a former editor of The New England Journal of Medicine, of the new study. “They are absolutely right on.”
Potentially deadly immune responses occur when a person’s immune system responds to what it perceives as danger signals, including toxic molecules from bacteria, viruses, fungi, or proteins released from cells damaged by trauma or burns, said Dr. Clifford S. Deutschman, who directs sepsis research at the University of Pennsylvania and was not part of the study.
The ramped-up immune system releases its own proteins in such overwhelming amounts that they make capillaries leak. The leak becomes excessive, and serum seeps out of the tiny blood vessels. Blood pressure falls, and vital organs do not get enough blood. Despite efforts, doctors and nurses in an intensive-care unit or an emergency room may be unable to keep up with the leaks, stop the infection or halt the tissue damage. Vital organs eventually fail.
The new study, which took 10 years and involved 39 researchers from across the country, began by studying white blood cells from hundreds of patients with severe burns, trauma or sepsis to see what genes are being used by white blood cells when responding to these danger signals.
The researchers found some interesting patterns and accumulated a large, rigorously collected data set that should help move the field forward, said Ronald W. Davis, a genomics expert at Stanford University and a lead author of the new paper. Some patterns seemed to predict who would survive and who would end up in intensive care, clinging to life and, often, dying.
The group had tried to publish its findings in several papers. One objection, Dr. Davis said, was that the researchers had not shown the same gene response had happened in mice.
“They were so used to doing mouse studies that they thought that was how you validate things,” he said. “They are so ingrained in trying to cure mice that they forget we are trying to cure humans.”
“That started us thinking,” he continued. “Is it the same in the mouse or not?”
The group decided to look, expecting to find some similarities. But when the data were analyzed, there were none at all.
“We were kind of blown away,” Dr. Davis said.
The drug failures became clear. For example, often in mice, a gene would be used, while in humans, the comparable gene would be suppressed. A drug that works in mice by disabling that gene could make the response even more deadly in humans.
Even more surprising, Dr. Warren said, was that different conditions in mice — burns, trauma, sepsis — did not fit the same pattern. Each condition used different groups of genes. In humans, though, similar genes were used in all three conditions. That means, Dr. Warren said, that if researchers can find a drug that works for one of those conditions in people, the same drug might work for all three.
The study’s investigators tried for over a year to publish their paper showing that there was no relationship between the genetic responses of mice and those of humans. They submitted it to the publications Science and Nature, hoping to reach a wide audience. It was rejected from both.
Science and Nature said it was their policy not to comment on the fate of a rejected paper, or whether it had even been submitted to them. But, Ginger Pinholster of Science said, the journal accepts only about 7 percent of the nearly 13,000 papers submitted each year, so it is not uncommon for a paper to make the rounds.
Still, Dr. Davis said, reviewers did not point out scientific errors. Instead, he said, “the most common response was, ‘It has to be wrong. I don’t know why it is wrong, but it has to be wrong.’ ”
The investigators turned to the Proceedings of the National Academy of Sciences. As a member of the academy, Dr. Davis could suggest reviewers for his paper, and he proposed researchers he thought would give the work a fair hearing. “If they don’t like it, I want to know why,” he said. They recommended publication, and the editorial board of the journal, which independently assesses papers, agreed.
Some researchers, reading the paper now, say they are as astonished as the researchers were when they saw the data.
“When I read the paper, I was stunned by just how bad the mouse data are,” Dr. Fink said. “It’s really amazing – no correlation at all. These data are so persuasive and so robust that I think funding agencies are going to take note.” Until now, he said, “to get funding, you had to propose experiments using the mouse model.”
Yet there was always one major clue that mice might not really mimic humans in this regard: it is very hard to kill a mouse with a bacterial infection. Mice need a million times more bacteria in their blood than what would kill a person.
“Mice can eat garbage and food that is lying around and is rotten,” Dr. Davis said. “Humans can’t do that. We are too sensitive.”
Researchers said that if they could figure out why mice were so resistant, they might be able to use that discovery to find something to make people resistant, too.
“This is a very important paper,” said Dr. Richard Hotchkiss, a sepsis researcher at Washington University who was not involved in the study. “It argues strongly — go to the patients. Get their cells. Get their tissues whenever you can. Get cells from airways.”
“To understand sepsis, you have to go to the patients,” he said.
http://www.nytimes.com/2013/02/12/science/testing-of-some-deadly-diseases-on-mice-mislead-report-says.html?pagewanted=2&_r=0&hp
Red Flags for Biotech Investors Part I
Phase III Enabling Studies
Proof-of-Confidence (POC) Trials
As a prerequisite to licensing, the majority of mid- to large-cap pharma companies require comparative in vivo
data demonstrating superiority over a contemporary standard of care. If technically possible, such data
should be generated during preclinical development and subsequently in Phase II. As an aside, randomized
Phase II trials are often referred to as Proof-of-Confidence (POC) studies as they are intended to provide data
that portend success and justify investment in a Phase III trial. Companies that initiate Phase III studies in the
absence of such data often do so without a partner and should be viewed with skepticism from an investment perspective. The
obvious reason for not conducting a POC trial is a lack of confidence in the asset, not funding or timing as
some would have you believe.
more... http://www.biotechinvestorsnetwork.com/#!feature-2/c1bc6
ONCY - Oncolytics Biotech announces additional positive REOLSYIN clinical trial data from Phase 2 Study in squamous cell carcinoma of the lung (3.57)
Co announced results examining percent overall tumour shrinkage data from its U.S. Phase 2 clinical trial in patients with squamous cell carcinoma of the lung (SCCLC) using intravenous administration of REOLYSIN in combination with carboplatin and paclitaxel (REO 021). The analysis examined percent best overall tumour changes between pre-treatment and up to six treatment cycles. Of 20 evaluable patients, 19 (95%) exhibited overall tumour shrinkage, (mean (20 patients): 33.7% shrinkage). "Based on these findings we intend to continue to look at REOLYSIN as a treatment for cancers of the lung and cancers that metastasize to the lung." The study enrolled patients with metastatic or recurrent squamous cell carcinoma of the lung. The primary endpoint of the study is objective tumour response rates, and the secondary objectives include progression free survival and overall survival. To date, the Company has observed nine partial responses (PR), nine stable disease (SD) and three progressive disease (PD) by RECIST criteria for a disease control rate (complete response (CR) + PR + SD)) of 86%. The study continues to enroll patients.
Read more: http://www.briefing.com/InPlayEq/InPlay/InPlayDual.htm#ixzz2KJmgIW00
Under Creative Commons License: Attribution
Follow us: @Briefingcom on Twitter | Briefingcom on Facebook
Never heard of Aegis? Their focus is on small cap bios... with a specialty for the rs + raise... i.e. SGYP, LPTN
Here's some of their deals...
http://www.aegiscapcorp.com/transactions/recenttransaction/
I'm curious if anyone has an opinion on Aegis or their lead Biotech analyst Raghuram "Ram" Selvaraju.
Here's an interview he did in the Life Science report...
http://www.thelifesciencesreport.com/pub/na/14673
Raghuram Selvaraju
Aegis Capital Corp.
Raghuram "Ram" Selvaraju's professional career started at the Geneva-based biotech firm Serono in 2000, where he discovered the first novel protein candidate developed entirely within the company. He subsequently became the youngest recipient of the company's Inventorship Award for Exceptional Innovation and Creativity. Selvaraju started in the securities industry with Rodman & Renshaw as a biotechnology equity research analyst. He was the top-ranked (#1) biotech analyst in The Wall Street Journal's "Best on the Street" survey (2006) and went on to become head of healthcare equity research at Hapoalim Securities, the New York-based broker/dealer subsidiary of Bank Hapoalim B. M., Israel's largest financial services group. While at Hapoalim, Selvaraju was regularly featured in The Wall Street Journal, Barron's, BioWorld Today, and Reuters/AP. He was also a regular guest on the Bloomberg TV program "Taking Stock," appeared with Bloomberg TV's on-air correspondents Betty Liu and Gigi Stone and was a guest on CNBC's "Street Signs with Herb Greenberg." He is currently an analyst with Aegis Capital Corp.
Small-molecule drug drives cancer cells to suicide
Studies in mice show therapy is effective even in hard-to-treat brain tumours.
Zoe Cormier
07 February 2013
Three weeks after implantation with a brain tumour, mice treated with a new drug were in recovery (right), compared with untreated mice (left, tumour shown in colour).
Cancer researchers have pinned down a molecule that can kick-start the body’s own tumour-destroying systems, triggering cell death in cancerous but not healthy tissue in mice.
The molecule, TIC10, activates the gene for a protein called TRAIL (tumour-necrosis-factor-related apoptosis-inducing ligand), which has long been a target for cancer researchers looking for drugs that would avoid the debilitating effects of conventional therapies.
“TRAIL is a part of our immune system: all of us with functional immune systems use this molecule to keep tumours from forming or spreading, so boosting this will not be as toxic as chemotherapy,” says Wafik El-Deiry, an oncologist at Pennsylvania State University in Hershey and lead author of the study, which is published today in Science Translational Medicine1.
Experiments showed that TIC10 had potent effects against a variety of tumours, including breast, lymphatic, colon and lung cancer. It was especially effective at triggering cell suicide in glioblastoma, a kind of brain tumour that is notoriously difficult to treat2. Mice with glioblastomas that were treated with TIC10 and bevacizumab — a drug used against diseases including brain tumours, and sold under the name Avastin — survived three times as long as untreated mice. However, they survived only 6% longer than mice treated with bevacizumab alone.
Quick and collaborative
El-Deiry says that TIC10 is so effective because it is much smaller than proteins that have previously been tested as TRAIL-based drugs. The molecule is so compact that it can cross the blood–brain barrier, which separates the main circulatory system from the brain. This barrier normally acts to prevent hazardous agents such as microbes from infecting the brain, but can also thwart anti-cancer drugs by keeping them out. “We didn’t actually anticipate that this molecule would be able to treat brain tumours — that was a pleasant surprise,” says El-Deiry.
Furthermore, it seems that TIC10 activates the TRAIL gene not only in cancerous cells, but also in healthy ones. This gives it enormous potential to create a 'bystander effect', in which apoptosis — or cell death — is induced in cancer cells immediately next to healthy ones. Healthy cells are also stimulated to increase the amount of TRAIL receptors on their cell surface. These receptors can then bind to the adjacent cancerous cells, triggering their demise. “It’s almost like TRAIL-plus — it does so much more,” says El-Deiry.
Tough TRAIL
This is by no means the only mechanism thought to trigger cell death in cancer. In particular, cancer researchers have been developing a number of drugs, including TRAIL-based therapeutics, that work by activating the cellular messenger tumour protein 53 (p53). But p53-based methods are not always effective, says El-Deiry. "Most tumours have dysfunctional p53, so in order to develop new therapeutics for cancer, one needs them to be effective in tumours with mutated p53,” he explains. His team's approach bypasses p53 entirely.
Although the study was limited to mice, the team is confident that a similar approach would work in humans. Other researchers are sceptical, in part because TRAIL-based strategies have not lived up to past hype.
The potential for TRAIL to usher in a new age in cancer therapy was first identified in the mid-1990s3. However, although early clinical trials for TRAIL-based therapies showed little toxicity, they were not very successful at treating cancer, says Andrew Thorburn, an oncologist at the University of Colorado Denver, who co-authored a review on the subject last year4. “All the large clinical trials found no significant survival benefit to adding TRAIL-based therapeutics to standard treatments,” he ads. Many large biomedical research groups have shelved their TRAIL-based drugs.
Nature doi:10.1038/nature.2013.12385
http://www.nature.com/news/small-molecule-drug-drives-cancer-cells-to-suicide-1.12385
Verastem announces publication of data for VS-5584 in Molecular Cancer Therapeutics; VS-5584 demonstrated 'potent and highly selective' activity against class 1 PI3K enzymes and dual-inhibitory actions against mTORC1 and mTORC2 (9.75)
VS-5584 demonstrated potent and highly selective activity against class 1 PI3K enzymes and dual-inhibitory actions against mTORC1 and mTORC2. The compound was profiled across >400 kinases covering all major families of the human kinome. In addition to the biochemical effects, VS-5584 exhibited broad anti-tumor efficacy, including tumor regression, across multiple human tumor models in the published study.
"We are currently evaluating VS-5584 in IND-enabling toxicity studies prior to entry into a Phase 1 trial...We anticipate initiating clinical testing of VS-5584 during the second half of 2013 in patients with advanced cancers. In addition to safety, the study will evaluate initial signs of clinical activity and cancer stem cell inhibition."
Read more: http://www.briefing.com/InPlayEq/InPlay/InPlayDual.htm#ixzz2K7tz9Eib
New cancer detection method right around the corner
It will now be possible to detect cancer by measuring the elasticity of tumours. The method is cheap, safe and radiation-free.
will replace X-ray, CT, MR and PET..
http://www.apollon.uio.no/english/articles/2013/elastography.html
tech from French co. Supersonic Imagine
http://www.supersonicimagine.com/
looks like they are preparing an IPO...
>Access to this information is restricted to French residents that are physically present in France, and international qualified investors that, in any event, are located outside the United States, Canada, Japan and Australia.<
http://www.supersonicimagine.com/financial/entry
Weekly Biotech/Pharma Volatility Tracker -- CLSN crashes on failed trial, KERX soars
CLSN crashed over 80% today following the failure of a Phase 3 trial for ThermoDox. KERX has nearly tripled on positive results for Zerenex. Check out the "Recent Events" section and Anticipated Movers list below for more information on these catalysts and to identify others in the coming weeks. Finally, be sure to use our Calendar of Upcoming Events to prepare for the many catalysts scheduled for 2013.
Recent Events
This morning Celsion (CLSN) shares plummeted over 80% after the company announced that ThermoDox in combination with radiofrequency ablation did not meet the primary endpoint of the Phase 3 HEAT Study in patients with hepatocellular carcinoma, also known as primary liver cancer. Expectations were very high, evidenced by the stock's run from below $2 to highs of $9.44 over the last six months, however, doubt began to set in as more and more time passed without an announcement about the trial. Management said it will continue to examine the data but that it "was not close" to showing a statistically significant positive effect. Celsion has two ongoing Phase 2 trials with ThermoDox: DIGNITY in breast cancer and ABLATE in colorectal liver metastases. Celsion was listed on our Anticipated Movers table last week.
Keryx Pharmaceuticals (KERX) has had an incredible week, nearly tripling from $3.43 to highs of $9.98. On Monday the company announced successful top-line results from the long-term Phase 3 study of Zerenex (ferric citrate), the Company's ferric iron-based phosphate binder drug candidate, for the treatment of elevated serum phosphorus levels, or hyperphosphatemia, in patients with end-stage renal disease on dialysis. In this study, Zerenex met the study's primary endpoint, demonstrating a highly statistically significant change in serum phosphorus versus placebo over the four-week Efficacy Assessment Period of the study. In addition, Zerenex met the key secondary endpoints of increasing ferritin and transferrin saturation and reducing the use of intravenous iron and erythropoiesis-stimulating agents. Analysts have been very positive on the stock, raising price targets as high as $15. Yesterday the company announced a $55 million offering of common stock to capitalize on the move. The offering of 8.234 million shares was priced at $8.49 per share. Keryx was listed on our Anticipated Movers table last week.
Isis Pharmaceuticals (ISIS) was another winner, gaining as much as 15% on Wednesday following the approval of KYNAMRO (mipomersen sodium). KYNAMRO, given as a 200 mg weekly subcutaneous injection, is indicated as an adjunct to lipid-lowering medications and diet to reduce low density lipoprotein-cholesterol (LDL-C), apolipoprotein B (Apo B), total cholesterol (TC), and non-high density lipoprotein-cholesterol (non HDL-C) in patients with homozygous familial hypercholesterolemia (HoFH). Isis is partnered with Genzyme, a Sanofi (SNY) company, for the drug and received a $25 million milestone payment upon the approval. Aegerion Pharmaceuticals (AEGR), which recently received approval and launched its own HoFH drug named Juxtapid, saw a slight decline on the approval. It is believed that KYNAMRO will be cheaper than Juxtapid, so it will be interesting to see how the two drugs compete. Isis was listed on our Anticipated Movers table last week.
Though shares are essentially unchanged, Merck (MRK) received some good news on Monday. The FDA approved OXYTROL FOR WOMEN (oxybutynin transdermal system, 3.9 mg/day), the first and only over-the-counter treatment for overactive bladder in women.
Furiex Pharmaceuticals (FURX) is up over 50% this week on the FDA approval of NESINA (alogliptin) and fixed-dose combinations OSENI (alogliptin and pioglitazone) and KAZANO (alogliptin and metformin HCl) for the treatment of type 2 diabetes in adults as adjuncts to diet and exercise. Furiex received a $25 million milestone payment from Takeda Pharmaceutical (TKPYY) as a result of the approval and will receive royalties on sales in the U.S.
Idenix Pharmaceuticals (IDIX) popped nearly 25% on Monday after announcing a collaboration with Janssen, a Johnson & Johnson (JNJ) company, for the clinical development of all-oral direct-acting antiviral hepatitis C (HCV) combination therapies. The collaboration will evaluate combinations including IDX719, Idenix's once-daily pan-genotypic NS5A inhibitor, simeprevir (TMC435), a once-daily protease inhibitor jointly developed by Janssen and Medivir AB, and TMC647055, a once-daily non-nucleoside polymerase inhibitor, boosted with low dose ritonavir, being developed by Janssen. Shares of Idenix have been unable to hold on to gains and are back to pre-announcement levels.
Repros Therapeutics (RPRX) has fallen approximately 35% this week. On Monday the company announced that clinical results from its first pivotal study, ZA-301, of Androxal in the treatment of secondary hypogonadism will not be available until the third quarter of 2013. Results were expected in the second quarter. The delay was due to one trial site's patient population being markedly different from the other 16 sites. Repros is hoping to transfer already enrolled patients from an identical trial to make up for the 40 patients that were dropped from the 151 patient study.
Anacor Pharmaceuticals (ANAC) shares have fallen over 20% since Tuesday. The company announced results from the first of two Phase 3 trials of tavaborole, its topical anti-fungal for onychomycosis, a fungal infection of the nail and nail bed. Tavaborole achieved a high degree of statistical significance on all primary and secondary endpoints, however, the Street was not overly impressed with the data. Just 6.5% of patients met the primary endpoint of "complete cure." This does not particularly stand out against other treatment options currently available.
ARCA biopharma (ABIO) shares have surged since yesterday's news that the company has planned a new adaptive Phase 3 trial for its drug Gencaro in atrial fibrillation. Medtronic (MDT) has signed a non-binding Letter of Intent to collaborate on the initial, Phase 2B portion of the proposed trial.
BioClinical (BIOC) received a $7.25 per share buyout offer from JLL Partners. The price represents a premium of 23.2% over its average closing price for the 90 days ended January 29, 2013, and 28.7% over the average price for the 52-week period ended January 29, 2013.
Ventrus Biosciences (VTUS) shares rose over 50% from Monday to Tuesday on no apparent news. The company quickly took advantage of the price appreciation and announced a $20 million offering of common stock and convertible preferred stock. The common stock portion of the financing was priced at $2.50 per share, well off highs of $3.92.
Lastly in news, Vanda Pharmaceuticals (VNDA) declined 10% this morning following negative Phase 2b/3 trial results. The study of tasimelteon as a monotherapy in the treatment of patients with Major Depressive Disorder did not meet the primary endpoint of change from baseline in the Hamilton Depression Scale (HAMD-17) after 8 weeks of treatment as compared to placebo.
A number of stocks saw declines following stock offerings, including BG Medicine (BGMD), Arrowhead Research (ARWR), and Anthera Pharmaceuticals (ANTH). There were also a few notable movers on earnings, including Nordion (NDZ) +10.5%, Haemonetics (HAE) -8.9%, Mead Johnson (MJN) +11.8%, and Cardiovascular Systems (CSII) +18.1%.
Read more: http://www.briefing.com/DisplayArticle/Article.aspx?ArticleId=NS20130131142140SpecialReports#ixzz2Jf6reoZt
Under Creative Commons License: Attribution
Follow us: @Briefingcom on Twitter | Briefingcom on Facebook
The Value Of A Pricey Orphan Drug: Nader Explains
By Ed Silverman // February 1st, 2013 // 8:45 am
Last month, the latest in a growing number of orphan drugs was approved by the FDA. In this instance, the Gattex treatment for short-bowel syndrome from NPS Pharmaceuticals (NPSP) was priced at $295,000, one of several in the past year that will cost $150,000 or more per patient per year. Although insurers regularly cover orphan drugs, particularly those in the so-called ultra-orphan category, the trend has raised questions about the ability of the rising price tags. We spoke briefly with NPS ceo Francois Nader about the decision making for Gattex…
Pharmalot: Given the discussion about orphan drug pricing, tell me about the value proposition we hear about…
Nader: Frankly, it was on our mind from day one when we started developing Gattex. And it’s on the mind of any company in the orphan space. The model is not specific to any product. It could be applied to a number of possibilities… But the first criteria to answer is whether the indication we’re pushing for is truly meeting an unmet medical need – a market not satisfied by the absence of any alternative. That’s a fundamental equation that any of us in the pharmaceutical business, in general, should ask ourselves, but specifically, in the orphan case…
We don’t have the luxury of running broad and comprehensive and multiple epidemiological studies, though. It’s an art and a science. We talk to payers to estimate the burden of illness based on their data… The issue is what does the drug offer to mitigate the condition? Does it meet that unmet medical need? And does it help save money and help lower overall healthcare costs? Does it reduce the direct and indirect costs related to the social aspect of many conditions and improve quality of life and daily living?
…The final point is to determine the willingness to pay to serve a very small population… In this case, there are 3,000 to 5,000 patients for Gattex total in the United States. That’s a very small population. This is where the notion of being willing to pay kicks in. Beyond daily living improvements, is society willing to incentivize companies, like ours, to embark on a (drug development) program such as this?… This is a model we follow and, frankly, I recommend that others follow as well.
Pharmalot: So you’re saying, the case you’re making, is the drug can lower costs down the road?
Nader: There is this inaccurate assumption that orphan diseases are not costing anything and, therefore, new drugs are, in a way, adding to overall costs. I think it’s a misperception. .. There are about 7,000 orphan conditions in the United States, and about 20 million Americans who suffer from orphan conditions… These patients are costing society a lot of money. Most are debilitated and cannot really take care of their conditions. And so there is an expense from a direct and indirect perspective. Many cannot work and, therefore, contribute to society. And they have life expectancies that can lead to premature deaths.
Pharmalot: Initially, the pricing was to have been about one-third of the cost announced and the patient population is also much lower than what had been said earlier. Why did that change?
Nader: We did prevalence studies in which the sample size is extremely small and so there’s a risk of multiplying the error by extrapolating… We conducted three prevalent studies with three different vendors and all methodologies were accepted and numbers (of patients) were consistently (shown to be) between 10,000 and 15,000, until we started really counting patients from a bottoms up approach. One element that was important in the strategy was to count patients managed by the top five home infusion companies in the country. And they claim they have about 30 percent of the home infusion market. They were asked how many short-bowel syndrome patients they have and they each said about 1,000.
It was very late in the game when we came up with this surprising number. At that point, we went to other companies in similar situations and found, unfortunately, it was not unusual for companies to rely prevalence studies in their external communications until they were able to count patients… Gattex is not unique, because it’s not unusual to have a dichotomy between prevalence, which gives you 10,000 to 15,000, and an actual addressable population, which gives you 3,000 to 5,000… The lower number of patients puts us in the ultra-orphan space, which triggers a higher premium.
Pharmalot: How this is conveyed to payers?
Nader: Our overarching concern with payers was not to take payers for granted. We didn’t believe they would automatically cover (Gattex) because it’s an orphan drug… Our drug is a pharmacy benefit and home infusion is a medical benefit, so it was important to bridge that… Medical directors have the clinical part of the equation and pharmacy have the drug and cost part of the equation…
From the payer’s perspective, there’s been a gigantic shift in total cost. I think 80 percent of drugs currently reimbursed are generics and we haven’t seen the end of it… There’s been a significant shift in the mix between generics and ethical drugs, which means (payers) have, in general, a lower budget for drugs as we knew it five or 10 years ago…
But I believe there’s a moral obligation to find treatments for these patients… The orphan space has become very trendy, but up until three or four years ago, these were called neglected disease… As a society, we have to think: ‘Should we continue to neglect the disease and the patients?’ The answer, so far, has been, ‘No, we should not.’ And so, we’ve seen an emergence in treating orphan conditions and a willingness to pay.
Pharmalot: There’ s also growing concern that the willingness may not always be there. Meanwhile, you have programs to help patients pay for the drug. How does that work?
Nader: For Gattex, there is a combination of funds that are earmarked internally and also funds coming directly from non-profits (such as the National Organization for Rare Diseases and Patient Access Network Foundation) devoted to supporting this kind of effort… For Medicare patients, we can’t do it ourselves, so we refer to non-profits that help them with co-pays… For those who fall through the cracks, we help them with free goods, or drugs. Fortunately, it’s a small number… Usually the ceiling or maximum a patient would pay is $6,000 or $7,000. Certainly, it’s not 20 percent, or in the range of $60,000. But for the payer, I don’t see a difference. What they reimburse is fixed and the difference has to come from somewhere. In this particular case, it’s a joint effort between patient and company.