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"ABBV expects Japan to approve V-Pak during 4Q15."
I think ABBV already gained V-Pak approval in Japan near the end of 3Q15:
http://www.fiercepharmaasia.com/story/abbvie-wins-viekirax-nod-japan-expected-competition-seen-tight/2015-09-29
http://abbvie.mediaroom.com/2015-09-28-AbbVies-VIEKIRAX-ombitasvir-paritaprevir-ritonavir-tablets-Receives-Approval-in-Japan-for-the-Treatment-of-Genotype-1-Chronic-Hepatitis-C
V-Pak Global Sales $231 mil in Q1:
http://www.sec.gov/Archives/edgar/data/1551152/000110465915029533/a15-9575_1ex99d1.htm
7:01 pm AbbVie: Investigational chronic hepatitis C treatment granted priority review in Japan (ABBV) : Co announced that the Japanese Ministry of Health, Labour and Welfare (:MHLW) has granted priority review for its investigational, two direct-acting antiviral treatment of ombitasvir/paritaprevir/ritonavir. This all-oral treatment is interferon (IFN) and ribavirin (RB.V)-free and will be dosed once daily. The MHLW grants priority review to certain medicines on the basis of clinical usefulness and severity of the disease, including diseases like hepatitis C, which affects approximately 1.5 to 2 million people in Japan. AbbVie's investigational hepatitis C treatment was submitted for marketing approval in Japan in February 2015. The New Drug Application is for the treatment of patients with genotype 1 (GT1) chronic hepatitis C virus (:HCV) infection and is supported by the Phase 3 GIFT-I study in Japanese genotype 1b (GT1b) HCV patients.
http://finance.yahoo.com/news/inplay-briefing-com-055139997.html#abbv
Gilead agrees to Sovaldi price cuts in Germany
((EU DAA pricing looking pretty good so far))
http://www.biocentury.com/dailynews/company/2015-02-19/gilead-agrees-to-sovaldi-price-cuts-in-germany?utm_source=Twitter&utm_campaign=auto_social&utm_medium=web
Published on Thursday, February 19, 2015
Germany's statutory health insurer GKV-Spitzenverband said Gilead Sciences Inc. (NASDAQ:GILD) will offer a 12-week course of Sovaldi sofosbuvir for EUR 43,562 ($49,213), an 11% discount from its German list price of EUR 49,000 ($66,135) and a 44% discount from the regimen's wholesale acquisition price of $84,000 in the U.S. The discount will be retroactive to Jan. 23 and will last for three years (see BioCentury Extra, Feb. 4, 2014).
The discount is in line with what Gilead has said it expects for its HCV drugs in the U.S. this year. During its earnings call earlier this month, Gilead said it expected an adjusted gross to net of 46% in the U.S. for its HCV drugs Sovaldi and Harvoni ledipasvir/sofosbuvir. Last year, the company came to a similar agreement with France's Economic Committee of Health Products, pricing Sovaldi at EUR 41,000 ($51,058) for a 12-week course (see BioCentury Extra, Feb. 4).
At the Bio CEO and Investor conference last week, Gilead President and COO John Milligan said the European market will be a larger part of the Sovaldi business in 2015 compared to 2014, and that the discounts for Sovaldi in France are dependent on the volume of patients treated.
In the U.S., Gilead and AbbVie Inc. (NYSE:ABBV) have been agreeing to rebates with pharmacy benefits managers and payers for their respective HCV regimens in exchange for exclusive or semi-exclusive formulary status. A similar scenario has yet to unfold in Europe where AbbVie's Viekirax plus Exviera was approved last month (see BioCentury, Jan. 19).
AbbVie said the benefit assessment process for Viekirax plus Exviera has already begun in Germany and will take six months, after which pricing negotiations will begin. The U.K.'s NICE has set April 1 as the first committee meeting to discuss a technology appraisal for Viekirax plus Exviera, which is marketed as Viekira Pak in the U.S. Based on its latest 10-K filing, Germany is AbbVie's second largest commercial market. Gilead does not provide a similar breakdown of its commercial markets. Gilead did not respond to BioCentury's request for comments or the status of pricing negotiations for Harvoni in Germany. Harvoni was approved in Europe last November. NICE had its first appraisal meeting for Harvoni on Feb. 3 and has set June 2015 as the "anticipated publication" date for the technology assessment.
Benjamin Graham is rolling over in his grave. IMO the current enterprise value just does not make sense even assuming a very conservative forecast of royalty income over the next few years (especially given ENTA's current modest overall business expense structure). ABBV's guidance would need to be off by a mile for the current valuation to make sense. IMO ABBV is too big a company to make such a large error on guidance even though its still early in the launch. Also, IMO they have nothing to gain by lying about guidance.
The market for whatever reason seems to be disinterested in royalty based companies.
I always thought ENTA would need to put up good numbers to reach my next hoped for level of share price. I never thought a month ago that they would need to put up good numbers from a low $30s share price. Certainly is frustrating, especially when other biotechs I am interested in acquiring a significantly larger position are starting to run away from me.
Hard to believe the stock traded at $57 during the pre-market on the day the ESRX contract was announced. The stock is trading roughly where it was a year ago. Recent news flow has been good IMO. Friday ABBV basically guides that they will be paying ENTA $37 million plus in royalties in Q4 2015 on over $750 million of V-P Q4 sales with growth anticipated from there in 2016. Co. will be exiting 2015 with a cash hoard of several hundred million dollars in cash. Co. has a pipeline. $800 million market cap. Does not compute.
fwiw---Gilead, AbbVie Hep C Price Cuts Seen Hitting Sales
BY AMY REEVES, INVESTOR'S BUSINESS DAILY
02:13 PM ET
As the price war over the new hepatitis C drugs heats up, the 2015 consensus estimates for both may be too high, according to Deutsche Bank.
In two separate notes Tuesday and Wednesday, analyst Robyn Karnauskas calculated the prospects for AbbVie's (NYSE:ABBV) Viekira Pak and Gilead Sciences' (NASDAQ:GILD) Harvoni and Sovaldi after the two companies announced a series of exclusive agreements with payers and pharmacy benefit managers.
"ABBV has so far nailed down 7% of US lives (Express Scripts (NASDAQ:ESRX) national formulary) while GILD has been chosen as preferred for 30% of US lives (CVS (NYSE:CVS) and Anthem (NYSE:ANTM)," she wrote. "If we were to assume 10% market share for ABBV among non-exclusive/preferred lives, we see overall share for ABBV at 14% and US sales at $1.25 billion in 2015."
With added revenues from Europe, where the drugs in Viekira Pak are expected to launch this year both as a set and as separate products, Karnauskas arrived at total HCV sales of $2 billion vs. $2.7 billion consensus. However, she also expects Gilead is going to low-ball consensus due to the price discounts it's had to negotiate to compete with AbbVie.
"At worst case, we expect discounts in commercial channels to be 15% for Harvoni (5% Sovaldi) which coupled with government discounts (40% Harvoni, 30% Sovaldi) calculates to 22% overall discount for HCV franchise," she wrote, explaining that this could result in revenue guidance $1 billion lower than the present consensus of $28.6 billion. "If guidance comes $2.5 billion lower that would validate what PBMs (pharmacy benefit managers) are telegraphing regarding discounts."
AbbVie is due to report Q4 and 2015 guidance on Jan. 30. Gilead hasn't yet set a date for its report.
Despite these lowered estimates, Karnauskas maintained a buy rating on both stocks due to their pipelines full of other promising drug candidates. The stocks didn't react much on the stock market today: In afternoon trading, Gilead was down 0.5% while AbbVie was down 1.4%. Gilead moved back above its 50-day moving average on Tuesday while AbbVie continues to slide below that key level.
http://news.investors.com/technology/012115-735507-hepatitis-c-drugs-gilead-abbvie-may-miss-estimates.htm
"Those watching the launch through weekly prescription data from IMS Health (NYSE:IMS) were stymied by IMS' announcement that some of the prescriptions were not being reported due to "a contractual condition between a supplier and the manufacturer,""
http://news.investors.com/technology/010915-733997-abbv-shares-fall-on-bank-of-america-downgrade.htm?ref=HPLNews
IMS Reports AbbVie (ABBV) Viekira Pak Week 1 Scripts (GILD)
http://www.streetinsider.com/Analyst+Comments/IMS+Reports+AbbVie+%28ABBV%29+Viekira+Pak+Week+1+Scripts+%28GILD%29/10129523.html
January 2, 2015 7:12 AM EST
Gilead Sciences (NASDAQ: GILD) week 11 Harvoni TRx was 5381, down 17% week-over-week, according to RBC Capital citing IMS. Harvoni NRx was 2500, a decline of 26%. Harvoni+Sovaldi TRx was 7402, and NRx was 3177.
AbbVie (NYSE: ABBV) Viekira Pak week 1 TRx was 14.
Commenting, analyst Michael J. Yee of RBC said, "This is far lower compared to Sovaldi week 1 NRx of 151 (in midDecember) and Harvoni week 1 NRx of 444 (in mid-October). Viekira Pak's week 1 launch is comparable to JNJ (NYSE: JNJ) Olysio week 1 NRx of 10; VRTX Incivek week 1 NRx of 14."
"As we've written in previous notes, we expect ABBV to gain low-single-digit share of NRx and pick up towards ~5-10% over time through Q1:15. GILD's Harvoni and ABBV's Viekira Pak are only competing within the 70-75% GT1 patients, as GILD's Sovaldi is the only approved regimen for GT2,3 patients," he added.
FDA approves Viekira Pak to treat hepatitis C
For Immediate Release
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm427530.htm
December 19, 2014
Release
The U.S. Food and Drug Administration today approved Viekira Pak (ombitasvir, paritaprevir and ritonavir tablets co-packaged with dasabuvir tablets) to treat patients with chronic hepatitis C virus (HCV) genotype 1 infection, including those with a type of advanced liver disease called cirrhosis.
Hepatitis C is a viral disease that causes inflammation of the liver that can lead to reduced liver function, liver failure or liver cancer. Most people infected with HCV have no symptoms of the disease until liver damage becomes apparent, which may take decades. According to the Centers for Disease Control and Prevention, about 3.2 million Americans are infected with HCV, and without proper treatment, 15-30 percent of these people will go on to develop cirrhosis.
Viekira Pak contains three new drugs—ombitasvir, paritaprevir and dasabuvir—that work together to inhibit the growth of HCV. It also contains ritonavir, a previously approved drug, which is used to increase blood levels of paritaprevir. Viekira Pak can be used with or without ribavirin, but it is not recommended for patients whose liver is unable to function properly (decompensated cirrhosis).
“The new generation of therapeutics for hepatitis C virus is changing the treatment paradigm for Americans living with the disease,” said Edward Cox, M.D., M.P.H., director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research. “We continue to see the development of new all-oral treatments with very high virologic response rates and improved safety profiles compared to some of the older interferon-based drug regimens.”
Viekira Pak is the fourth drug product approved by the FDA in the past year to treat chronic HCV infection. The FDA approved Olysio (simeprevir) in November 2013, Sovaldi (sofosbuvir) in December 2013 and Harvoni (ledipasvir and sofosbuvir) in October 2014.
Viekira Pak’s efficacy was evaluated in six clinical trials enrolling 2,308 participants with chronic HCV infection with and without cirrhosis. In different trials, participants were randomly assigned to receive Viekira Pak or placebo (sugar pill); Viekira Pak with or without ribavirin; or Viekira Pak with ribavirin for 12 or 24 weeks.
The trials were designed to measure whether the hepatitis C virus was no longer detected in the blood at least 12 weeks after finishing treatment (sustained virologic response, or SVR), indicating that a participant’s HCV infection has been cured. Results from multiple populations, including those considered difficult to treat, showed 91 to 100 percent of participants who received Viekira Pak at the recommended dosing achieved SVR. The recommended dosing for Viekira Pak is two ombitasvir, paritaprevir, ritonavir 12.5 milligrams (mg)/75 mg/50 mg tablets once daily and one dasabuvir 250 mg tablet twice daily.
The most common side effects reported in clinical trial participants were feeling tired, itching, feeling weak or lack of energy, nausea and trouble sleeping.
Viekira Pak is the eleventh new drug product with breakthrough therapy designation to receive FDA approval. The FDA can designate a drug as a breakthrough therapy at the request of the sponsor if preliminary clinical evidence indicates the drug may demonstrate a substantial improvement over available therapies for patients with serious or life-threatening diseases. Viekira Pak was reviewed under the FDA’s priority review program, which provides for an expedited review of drugs that treat serious conditions and, if approved, would provide significant improvement in safety or effectiveness.
Viekira Pak is marketed by AbbVie Inc., based in North Chicago, Illinois. Olysio is marketed by Raritan, New Jersey-based Janssen Pharmaceuticals. Sovaldi and Harvoni are marketed by Gilead Sciences, based in Foster City, California.
The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.
Enanta Pharmaceuticals Provides Update on its Collaboration Agreement with AbbVie
• Co-Development Option on Next-Generation Protease Inhibitor ABT-493 Not Exercised
• Net Sales Allocations for ABT-450-Containing Regimens Finalized
http://finance.yahoo.com/news/enanta-pharmaceuticals-provides-collaboration-agreement-205200624.html?soc_src=mediacontentstory
WATERTOWN, Mass.--(BUSINESS WIRE)--
Enanta Pharmaceuticals, Inc., (ENTA) a research and development-focused biotechnology company dedicated to creating small molecule drugs in the infectious disease field, today announced that it has decided not to exercise its co-development option for ABT-493, Enanta’s next-generation protease inhibitor for hepatitis C virus (HCV) being developed in Enanta’s collaboration with AbbVie. Per the original collaboration agreement signed in December 2006, Enanta will be eligible for certain regulatory approval milestones as well as royalties on net sales allocable to ABT-493 from worldwide sales of any ABT-493-containing regimens. Enanta also announced that it has reached agreement with AbbVie regarding the net sales allocations for royalty calculations for ABT-450-containing regimens, as well as any regimens containing ABT-493. ABT-450 is the first clinical-stage protease inhibitor candidate developed within the Enanta-AbbVie collaboration, and ABT-493 is the second.
“We believe that the development and commercialization of our HCV protease assets, ABT-450 and ABT-493, are in good hands with the expertise and resources of a global biopharmaceutical company such as AbbVie,” stated Jay R. Luly, Ph.D., President and CEO. “At this time, we have decided it is better to use our financial resources generated by these partnered assets to advance our other internal proprietary candidates for HCV, including our newly reacquired NS5A program, and to pursue the growth of our pipeline beyond HCV with additional candidates in infectious disease and other indications.”
Net Sales Allocations for Protease-Inhibitor-Containing Regimens Used to Calculate Annual Royalties
Under the original agreement with AbbVie, Enanta is entitled to receive payments for regulatory and reimbursement approval milestones, as well as annually tiered royalties per product, ranging from the low double digits up to twenty percent, on AbbVie’s worldwide net sales allocable to the collaboration’s protease inhibitor product. With the amended agreement, the following percentages of worldwide net sales of ABT-450-containing regimens will be the net sales then used to calculate annual royalties payable to Enanta:
Protease Inhibitor-Containing
Regimens
Percentage of Annual Net
Sales Used for Enanta
Royalty Calculation
ABT-450-containing 3-DAA regimen
(ABT-450/r, ombitasvir and dasabuvir) 30%
ABT-450-containing 2-DAA regimen
(ABT-450/r, ombitasvir) 45%
For any HCV treatment regimen containing ABT-493, net sales for
royalty purposes will be determined by dividing AbbVie’s worldwide
net sales of the regimen by the number of DAAs in the regimen (e.g.
50% of net sales for a 2-DAA regimen and
33 1/3% of net sales for a 3-DAA regimen).
In addition, although ABT-493 is not currently being developed for sale in combination with any active ingredient other than a DAA, if it were, then there would be a further adjustment to net sales of the regimen for royalty purposes based on the relative value of any non-DAA in the regimen sold by AbbVie.
Protease Inhibitor Collaboration with AbbVie
In December 2006, Enanta and Abbott announced a worldwide agreement to collaborate on the discovery, development and commercialization of HCV NS3 and NS3/4A protease inhibitors and HCV- protease-inhibitor-containing drug combinations. ABT-450 and ABT-493 are protease inhibitors identified through the collaboration. Under the agreement, AbbVie is responsible for all development and commercialization activities for ABT-450, the collaboration’s lead compound that has been submitted for approval in the United States and the European Union as part of a multi-drug regimen. Enanta received $57 million in connection with signing the collaboration agreement and $95 million in subsequent clinical and regulatory milestone payments, and is eligible to receive up to an additional $155 million in payments for regulatory and reimbursement approval milestones, as well as annually tiered, double-digit royalties per product on AbbVie’s worldwide net sales allocable to the collaboration’s protease inhibitors.
FWIW - just say my 1st ABBV hep C TV commercial. Pretty good ad - spoke to cures.
Dew, I guess you could deduct $5 per share from your valuation model:
http://finance.yahoo.com/news/enanta-regains-full-rights-ns5a-120000172.html
Balky payers, beware: Gilead eyes $95K-or-so price for Sovaldi combo pill
http://www.fiercepharma.com/story/balky-payers-beware-gilead-eyes-95k-or-so-price-sovaldi-combo-pill/2014-09-15?utm_medium=nl&utm_source=internal
September 15, 2014 | By Tracy Staton
Gilead Sciences ($GILD) has cracked the door on its pricing for the hepatitis C combo pill it's hoping to roll out next month. And here's the view: No "significant premium" to the current three-drug cocktail that includes Sovaldi, Gilead's current money-minting treatment.
The older regimen, which also includes ribavirin and interferon, runs $95,000 for one 12-week course, Gilead tells Reuters. (Sovaldi, of course, accounts for $84,000 of that.) The new pill's price will be competitive with that--and it's a better therapy to boot, a Gilead executive said.
"We are going to price this fixed-dose regimen based on those costs," EVP Gregg Alton told the news service. "We do plan on launching a better product without having a significant premium."
Regulatory changes are repeatedly impacting the bottom line for both government and commercial programs. Learn why manufacturers participate in government programs, the obligations associated with such participation, the interconnectivity between various government programs, and the link between commercial pricing and contracting on government pricing. Register Now!
That means Gilead is unlikely to "break the $100,000 barrier," ISI Group analyst Mark Schoenebaum said in a note on Friday. And that's about on par with what market-watchers have been expecting. Sanford Bernstein's Geoffrey Porges has pegged its list price right at $100,000, while RBC Capital Markets' Michael Yee had been betting on $95,000.
Studies have found that the new combo--Sovaldi plus Gilead's brand-new ledipasvir--can cure up to 99% of hep C patients, with results varying by viral genotype and patients' prior treatments. As with all of the next-generation hep C fighters soon to hit the market, the pill is much easier to tolerate than previous regimens, and it's all-oral.
But the "better regimen, all-but-par price" approach contains one big, fat misdirection: The lion's share of that older protocol's cost is Sovaldi. And that $84,000 tag has payers--and patients who can't get access to it--pulling out their hair in frustration.
For the argument in a nutshell, look no further than Oregon, where state officials are aiming for new restrictions on the drug, and Gilead is lobbying hard against them. According to The Oregonian, Gilead execs jetted over to meet with officials and state lawmakers in advance of a public hearing Monday.
The Gilead argument is, as always, that the super-expensive pill is a cure that will save big money on complications down the road. But Oregon's Medicaid program is worried about its budget now. Because of a waiver it gained in a 1990s Medicaid expansion, the state's program has unusual leeway to decide which treatments to pay for, so Oregon has leverage that other states--and private insurers--don't have.
So, Gilead is wheeling and dealing there, or trying. It says it's offering Sovaldi at Canada-level prices, or about $55,000 per course. But Medicaid officials say there's a string attached to that deal: Oregon would have to cover every patient with a prescription, no prerequisites.
Gilead has offered other payer-by-payer deals; for instance, its contract with the Veterans Administration covers Sovaldi at $47,000. To win coverage in the U.K.--where cost-effectiveness watchdogs usually wring discounts from drugmakers--it priced Sovaldi at $57,000. In March, the Pennsylvania Medicaid program said it had been paying $70,000 for Sovaldi plus two other drugs; that's most likely ribavirin and interferon rather than newer and more expensive alternatives such as Vertex Pharmaceuticals' now-abandoned Incivek. That would put Sovaldi's portion at about $59,000, give or take a few.
Meanwhile, Gilead just inked a Sovaldi access deal with a handful of generics makers, who'll turn out the hepatitis C pill in developing markets at vastly discounted prices. One of the companies involved, Hetero, says it figures on a $300 "benchmark" price.
Gilead is well practiced at withstanding the slings and arrows of pricing critics, what with its experience marketing pricey HIV drugs. But with new competition on the horizon in hep C, it may find itself vulnerable. AbbVie ($ABBV) and Bristol-Myers Squibb ($BMY) could well choose to undercut Gilead's pricing to gain market share. And private insurers might put those companies' meds on their formularies--and kick Gilead's off.
Competitive price discounts wouldn't just win favor with payers, but might help with doctors and patients, too. Consider this: One Oregon patient suffering from cirrhosis fought for 9 months to get a Sovaldi prescription, and now, her insurer is balking at paying for another drug in her cocktail--and her doctor is fed up. "He just went on about how bad Gilead is, how bad insurance is," the 67-year-old Linda Harrison told The Oregonian. "He said his office doesn't have time to do the appeals."
WSJ Editorial -- Medical Innovation Threat
The attack on a near-cure for Hepatitis C is a prelude to price controls.
Aug. 19, 2014 7:06 p.m. ET
http://online.wsj.com/articles/the-medical-innovation-threat-1408489613?_outlook
An invasive species has been introduced into the U.S. health innovation ecosystem, with a growing danger of permanent damage to the development of specialty drugs. The relentless assault on the price of Sovaldi is becoming a threat to the 30-year political balance that has energized the biomedical revolution.
Sovaldi is the kind of medicine that the drug scolds claim to want—a true scientific advance with a near-perfect cure rate for Hepatitis C, the liver-destroying virus that infects one of every 100 Americans and some 150 million world-wide. The old critique was that pharmaceutical discovery had stalled and the industry produced only me-too drugs. Now they attack Sovaldi because its price is $84,000 a patient.
The claim by the insurance industry and liberals is that the market is producing irrational and anticompetitive prices. So politicians are moving to do what comes naturally, which is transfer pricing control to government.
"A big part of our concern is not just Sovaldi, but all the other specialty drugs," said Mario Molina, the CEO of Molina Healthcare that runs Medicaid and ObamaCare plans in nine states, on a July earnings call. He added: "I think that the government needs to step in here and make sure that the market is rational. If we as a health plan want a rate increase, we have to go to our regulators and get it approved. There's no such thing going on in the pharmaceutical market. Right now, pharmaceutical companies can charge whatever they want, and I think there needs to be a rational basis for all of this."
In other words, time to blow up the durable consensus of the Hatch-Waxman law of 1984. In exchange for the staggering risk and investment to make a new drug, and the far too slow and adversarial FDA approval process, companies are granted intellectual property protection and the freedom to set their own prices as an incentive for research and development. The life of a pharma patent is now roughly a decade. After that the long-run interest in cheaper medicines is satisfied with generic copies, which now make up 86% of prescriptions filled.
Supposedly Sovaldi's maker, Gilead Sciences, GILD +0.69% has broken some Hatch-Waxman social compact by charging too much, but the critics never define the "correct" level and in any case this first-in-class cure is priced comparably to Hep C treatments with life-long toxic side effects. The critics seem to know the price of everything and the value of nothing, which in this case includes the benefit to patients and eradicating this disease in the U.S. by 2036, according to an MD Anderson Cancer Center analysis.
The health insurers say they merely want to secure lower prices for consumers and more transparency about how drug prices are determined. Democrat Ron Wyden and Republican Chuck Grassley of the Senate Finance Committee seem to have missed this subtlety.
In a recent letter to Gilead, the Senators question "the extent to which the market for this drug is operating efficiently and rationally" and suggest that Sovaldi's price "appears to be higher than expected given the costs of development." They go on to make 21 demands for information with 41 subparts and 28 footnotes, such as "an itemized accounting of research and development costs" including "separate line items for personnel costs, clinical studies, materials and supplies, licenses and fees" and on and on.
Disclosing such sensitive proprietary data can only be meant as prelude to price controls or another form of regulation that treats drug makers as public utilities. As America's Health Insurance Plans CEO Karen Ignani recently asked in these pages, "Do the prices reflect the cost of investment, or are we entering a new phase where monopolies approved under patent law are producing prices entirely untethered to the cost of developing drugs?" In Washington such questions are rarely rhetorical.
The reality is that drug prices have never been tethered solely to R&D and other spending incurred over the course of their narrow development, as Messrs. Wyden and Grassley seem to favor. Drug researchers are not oracles. Most of the some 700 Hep C projects across the biotech industry over the last two decades miscarried in the lab or in trials before Sovaldi emerged.
To the extent drug prices are rising, one reason is because researchers are asking more challenging clinical and biological questions. Only two of every 10 drugs on the market ever earn back enough money to match the cost of R&D and FDA approval before patents expire. Successful drugs thus underwrite the uncertain, failure-prone, time-consuming and often wasteful and even random process of scientific invention.
One irony of the Sovaldi debate is that insurers already use many pharmacy management methods to contain consumer drug costs, such as step therapy, prior authorization and tiered benefit designs. They help explain why premiums in the Medicare drug benefit will rise by all of a dollar a month next year. For Hep C, a new generation of treatments is forthcoming from AbbVie, ABBV -0.97% Bristol-Meyers BMY -0.43% Squibb and Merck. Are those me-too drugs, or competitive alternatives that will pull down costs? Just asking.
And if insurers really believe that the benefits of this drug aren't worth the money, then they should refuse to pay and say the market cannot bear $84,000 for a breakthrough. Memorial Sloan-Kettering oncologists mounted a 2012 boycott of a colorectal cancer medicine called Zaltrap that cost $11,000 a month and forced Sanofi SAN.FR -0.79% to cut the price in half.
***
We suspect the reason such a pricing ultimatum hasn't been made is that Sovaldi really does pass the cost-benefit test. The drug is nonetheless being demagogued to undermine the institutions and patent-certainty that make America the one market in the world that rewards medical progress as a sustainable financial enterprise.
We're told this Congress would never pass price controls, but don't be so sure. Populist wildfires burn in unpredictable directions—and might yet turn on Gilead's critics too. Advances in molecular biology, genetics, oncology, neuroscience and immunology could well produce therapies whose inventors charge now-unthinkable prices. Financial markets, insurance included, exist so consumers and businesses can afford large expenses over time like homes and education and for that matter jet engines.
If the insurance industry doesn't innovate beyond the status quo and develop modern financial products that allow patients to afford medicines like Sovaldi, consumers and politicians may conclude that insurers don't need to exist either.
Here is a comprehensive white paper historical review of 135 FDA approvals of rare disease drugs. Given the number of drugs approved on "administrative flexibility" and "case by case flexibility", I would guess that a lot depends on which way the wind happens to be blowing on any given day in Bethesda, Maryland come review time. A number of these drugs were approved on pretty skimpy evidence a decade or two ago. I doubt that many of these drugs would be approved today on the same level of evidence.
http://rarediseases.org/docs/policy/NORDstudyofFDAapprovaloforphandrugs.pdf
UPDATED: Watch out Gilead, Merck is mounting a hep C combo comeback
http://www.fiercebiotech.com/story/watch-out-gilead-merck-mounting-hep-c-combo-comeback/2014-04-10
April 10, 2014 | By John Carroll
Merck may be late to the blockbuster party with its new hepatitis C drugs, but the pharma giant is moving fast with a top contender boasting high cure rates.
Merck ($MRK) unveiled interim Phase II results for an oral combination of MK-5172, its NS3/4A protease inhibitor, and MK-8742, an NS5A, among patients with chronic HCV genotype 1 infection. After 12 weeks of therapy 42 of 43 patients--98%--demonstrated a sustained viral response. The combination plus ribavirin hit a 94% cure rate. And the drugs did it without any injections of interferon, which is widely hated by patients.
In recent months Gilead's ($GILD) Sovaldi has been taking the hepatitis C market by storm as it steams its way to a multibillion-dollar debut. An unqualified success by industry standards, the $84,000 price has produced a storm of controversy. Payers, led by the pharmaceutical benefit manager Express Scripts ($ESRX), have hit back, complaining that the drug is a budget buster and vowing to warehouse patients who can wait for other therapies that can do the job just as well or better.
That backlash has created an opportunity for developers like Merck. But it likely won't be first among the next round of competition. AbbVie ($ABBV) has been barreling along with its oral combo and Gilead also has its combination approach matching Sovaldi with ledipasvir, up for a review at the FDA with a decision due by early October. Still, given the size of this market, with millions of patients in the U.S. alone, even a late arrival by Merck could generate significant income. And the FDA, which has already provided Merck with "breakthrough" drug status for the combo, is likely to be under considerable pressure to hurry along rival therapies.
ISI's Mark Schoenebaum is optimistic that Merck--which has been marketing the fast-fading Victrelis--can break well past the $400 million sales projections circulating on Wall Street.
"As we pointed out yesterday…, consensus hep C numbers for MRK in the out-years seem very low to me," Schoenebaum noted Thursday morning. "Given the strength of today's data, I would expect analysts to begin raising their MRK hep C estimates fairly dramatically (perhaps 3x-8x) over the next year. MRK will very likely have definitive Phase III data in 2015.
The news is also likely to help restore some confidence in Merck's R&D operations, which have been undergoing a major reorganization after a 6-year drought of significant new drug approvals. The immuno-oncology drug MK-3475 has been the star program at Merck. But the pharma giant posted four Phase III trials for the hepatitis C drugs on clinicaltrials.gov, recently, giving it boasting rights for another closely-watched late-stage program. The studies are expected to wrap next spring.
"These Phase II results add to growing evidence for the potential efficacy of MK-5172 and MK-8742 for treatment of chronic HCV infection," said Dr. Eliav Barr, vice president, infectious diseases, Merck Research Laboratories. "These findings are integral to advancing our research of these investigational candidates into C-EDGE, the Phase 3 clinical program that will seek to more broadly evaluate the potential of MK-5172/MK-8742 in diverse patient populations."
- here's the release
http://www.fiercebiotech.com/press-releases/merck-announces-results-studies-evaluating-investigational-hepatitis-c-trea-0
Hepatitis C Drug Price Limiting State Medicaid Approvals
http://www.bloomberg.com/news/2014-03-05/hepatitis-c-drug-price-limiting-state-medicaid-approvals.html
By Drew Armstrong Mar 5, 2014 12:01 AM ET
The price of Gilead Sciences Inc. (GILD)’s $1,000-a-day hepatitis C pill is keeping state-run Medicaid programs from making it available to many of the people who are most likely to be infected with the disease.
People in Medicaid, the government health plan for the poor, are prime candidates for Gilead’s Sovaldi, which works better and carries fewer side effects than existing therapies. The $84,000 cost for the cure over 12 weeks, the most expensive medicine for the disease, has states from Pennsylvania to Colorado limiting its use to only the sickest patients, according to health officials and private insurers that manage care for Medicaid programs.
Hepatitis C, a virus infecting about 2.7 million in the U.S., is transmitted through blood, with those getting transfusions before 1992 and intravenous drug users most at risk. It can be symptomless for decades before it begins to scar the liver, leading to liver cancer in some cases, organ failure and the need for a transplant.
While cancer can hit anybody, poor minorities are more likely to be infected with hepatitis C, according to a study reported this month by the U.S. Centers for Disease Control and Prevention. The research found that patients with the disease were more likely to be black, less likely to finish high school than the average American and had an average annual income of less than $23,000.
“You’re talking about a condition that is going to be concentrated in low-income, minority patients,” said J. Mario Molina, chief executive officer of Molina Healthcare Inc. (MOH), which helps 11 states manage pharmacy benefits for 2.1 million Medicaid patients. “You’ve got socioeconomic class issues here that we don’t have with cancer.”
Screening Recommended
The CDC, based in Atlanta, recommends screening for everyone in the U.S. born from 1945 to 1965. Those on Medicaid, even if they’re found to be infected, face barriers to getting the latest and best medicines until their disease has already done damage.
“If you’ve got a patient who is advanced and has liver disease and is about to get a liver transplant, it makes sense to give treatment,” said Molina, whose company only approves the Gilead drug now in urgent cases. The question is “what do we do about everybody else?” he said.
If everyone in the U.S. with hepatitis C were treated with Sovaldi at its list price, it would cost $227 billion compared with the estimated $260 billion spent a year in the country for all drugs.
Cost Benefits
Gilead said the drug’s high cost pays for itself by avoiding future complications. “Older therapies were not sufficiently effective or tolerable to continue to be used as the standard of care,” said Gregg Alton, executive vice president of corporate and medical affairs for the Foster City, California-based company. “We will continue to work with payers to help them understand the scientific and medical evidence.”
Most other approved therapies for hepatitis C involve long courses of injections that boost the immune system, carry lower cure rates and produce side effects that can include nausea, anemia, insomnia and flu-like symptoms. That’s created a dilemma for states trying to balance rising health-care costs and the desire to get the best treatments to citizens.
While Victrelis, an older drug from Merck & Co., isn’t as effective, according to research, it’s priced at about $36,500 for 24 weeks of treatment, less than half the $84,000 listed cost of Sovaldi, according to Catamaran Corp. (CTRX), a Schaumburg, Illinois-based pharmacy benefits manager.
Pennsylvania covers about 100,000 patients through the state’s Medicaid program. It had two applications for Sovaldi as of last month, neither of which were approved by the state, said Terri Cathers, director of pharmacy for Pennsylvania’s Office of Medical Assistance Programs.
‘Sticker Shock’
“I’m not going to deny we were in sticker shock,” Cathers said by telephone. “If the drugs are going to give our patients the best therapy and get them to cure, we want to get them. But we want to be prudent about that.
‘‘I think that on a federal level, drug pricing needs to be addressed,’’ Cathers said.
The Centers for Medicare and Medicaid Services, which oversees Medicaid for the federal government, said it’s committed to working with states to make sure they have the best tools to get affordable drug prices.
Gilead, which says it may sell the drug in India for $2,000 for the 12-week regimen, tailors its price to the market. ‘‘Gilead’s global pricing model is based on a country’s ability to pay,” said Alton, the company executive.
Provider Concerns
In the U.S., Medicaid providers disagree with Gilead about whether they can afford the cost. “The federal government is going to have to step in and say there’s a concern about the public welfare, and we can’t allow companies to take advantage like this,” said Molina, who’s company is the fourth-biggest private Medicaid administrator. “Is what they’re charging really appropriate?”
WellPoint Inc. (WLP) manages claims for 4.4 million Medicaid patients in 19 states, and won’t approve a combination treatment of Sovaldi and another new drug -- Johnson & Johnson (JNJ)’s Olysio -- for anyone but patients with more advanced disease.
Sovaldi “is more costly but offers improved outcomes, particularly coupled with Olysio,” said Kristin Binns, a WellPoint spokeswoman. WellPoint plans to limit use of the two drugs together -- the most expensive therapy combination -- to just those with evidence of liver damage, Binns said.
Early Treatment
Gilead calls that a mistake. Using the drugs earlier produces better cures and results in fewer complications from the disease, Alton said in an e-mailed statement.
The new drug has arrived as the 2010 Patient Protection and Affordable Care Act, known as Obamacare, promises to add more than 12 million people to the Medicaid program in a nationwide expansion. At the same time, health-care costs for states continue to grow after doubling to 30 percent of state and local budgets from 1987 to 2012, according to a January report by the Pew Charitable Trusts.
State officials at Medicaid programs in Louisiana, California, Michigan and Florida said in interviews that they will only approve the use of Gilead’s Sovaldi on a case-by-case basis while they study how best to address the drug’s cost going forward.
In Colorado, officials advised doctors in a Feb. 19 letter that “new therapies for hepatitis C will not be approved” until the state finishes its review.
“Given the demand for the medication, the generally slow progression of the disease, and the rapidly changing landscape of the treatments available for hepatitis C, the department needs to do further evaluation and review to determine the the appropriate coverage criteria for Sovaldi,” officials wrote.
Doctor View
Doctors are also caught up in the debate over costs. Jonathan Fenkel, the director of Jefferson University Hospitals’ hepatitis C center in Philadelphia, has about 1,000 hepatitis C patients in his practice.
“I used to have an easy argument that treating hepatitis C was cheaper than paying for a liver transplant or liver cancer,” he said in a telephone interview. “But it’s getting a little closer.”
Some state policies may change over time.
In Pennsylvania, for example, the state’s pharmacy and therapeutics committee will meet in May to decide on a treatment policy for Sovaldi. Right now, the state pays a discounted price of about $70,000 for a course of Sovaldi and two other drugs given in combination, compared with $40,000 for an older regimen.
Cathers, the Pennsylvania Medicaid official, said she’s concerned that the high price of a drug like Sovaldi will have an effect that carries through in future years with other hepatitis C medicines.
“What are we going to have in the future when these new all-oral therapies come to market, are we going to see these escalate to $120,000?” Cathers said.
To contact the reporter on this story: Drew Armstrong in New York at darmstrong17@bloomberg.net
At $84,000 Gilead Hepatitis C Drug Sets Off Payer Revolt
http://www.bloomberg.com/news/2014-01-27/at-84-000-gilead-hepatitis-c-drug-sets-off-payer-revolt.html
By Drew Armstrong Jan 27, 2014 12:00 AM ET
As Gilead Sciences Inc. (GILD) touted its $1,000-a-pill hepatitis C cure to investors in a hotel ballroom in San Francisco last week, a group of about 20 protesters milled outside. “Gilead=Greed,” one sign read.
“I’m glad people have the new drugs, but I’m concerned about the prices,” said Orlando Chavez, 62, a hepatitis C and HIV counselor and one of the protesters. He worries that insurers will see Gilead’s price and force patients to try a less effective, older and cheaper therapy first, he said.
Chavez has good reason to worry.
Payers face billions of dollars in new drug costs as pharmaceutical companies develop increasingly complex products in the years ahead. Express Scripts Holding Co. (ESRX), Catamaran Corp. (CCT), Aetna Inc. and CVS Caremark Corp. (CVS) among others are already pushing back against the high cost of Gilead’s drug. They’re discussing how to pit similar drugs against each other, refusing coverage for some, or subjecting treatments to more review by outside experts and refusing to pay a premium based on one drug being more convenient to take than another.
Gilead’s new drug, Sovaldi, costs $84,000 for a 12-week treatment. Such breakthrough treatments and their stratospheric price tags have “absolutely” caused insurers to reconsider covering high-priced hepatitis, diabetes and other treatments, said Sumit Dutta, chief medical officer of Catamaran, the fourth-biggest U.S. pharmacy benefit manager, or PBM.
“You can’t manage exclusively by the techniques PBMs have used in the past,” Dutta said by telephone. “We’re seeing the shift, where payers are finally going to say, ’It’s $84,000, and the other therapy is $50,000 -- what am I getting?’”
Stock Valuation
For drugmakers and biotechnology companies that have zeroed in on high-priced treatments to replace blockbusters such as Lipitor, the Pfizer Inc. cholesterol drug that once drew more than $12 billion a year before losing ground to generics, the change may affect how shareholders value their stocks, according to Les Funtleyder, a health industry expert and author of the book “Health-Care Investing.”
“There’s been a feeling among investors that biotech drugs are immune from price competition,” Funtleyder said in an interview. “We’re getting to where we may have may reached a pain point.”
Prescription drugs make up an increasing share of U.S. health care spending. Spending on hepatitis C drugs alone is projected to rise seven-fold from $3 billion a year in 2011 to $21 billion in 2018, according to market research firm Decision Resources Group LLC. U.S. drug spending will grow 6.5 percent a year from 2015 to 2022, faster than overall health costs, according to the U.S. Centers for Medicare and Medicaid Services. That’s mostly driven by rising prices and a leveling off of generic drug use, according to the U.S. report.
Cost Debate
It will take Gilead three to six months since it was approved Dec. 6 to formalize coverage with payers and PBMs, said Chief Operating Officer John Milligan in an e-mail. In the meantime, most plans are covering it, he said.
When eventually combined with a second drug Gilead is studying, the regimen’s price could rise to $100,000 or more per year, compared to what Catamaran says is about $66,000 for the current standard of care.
That’s still cheaper than treating complications of hepatitis C, which can lead to liver damage or failure and the eventual need for transplant, said Gilead’s Milligan.
“In our conversations with payers, pricing is a consideration, but efficacy, safety and treatment guidelines are equally important,” Milligan said.
Tools Available
Besides payers already have plenty of tools to push back on costs and force patients to try cheaper medicines first, and they use them, said the drug industry’s Washington trade group, Pharmaceutical Researchers and Manufacturers of America. “Typically by the time the patients get through the various steps they need to get to the product, they really do need it,” said Lori Reilly, PhRMA’s head of policy.
Even so, payers are thinking twice before opening their wallets. Jeff Park, Catamaran’s chief financial officer, said some prescription plans managed by his company are already pushing patients to try older therapies first, moving to the more expensive ones only and only if they fail.
“You can get to these more expensive treatments,” Park said in an interview in San Francisco during the JPMorgan Chase & Co. health-care conference. But to do so, “you have to outweigh the costs of the first, more cost-effective treatment.”
That’s a big concern for patients and advocates such as Chavez who say that strategy will force them to stick with side-effect-heavy older hepatitis C treatments that rely on difficult weekly injections, making a patient feel as if they have the flu over and over again.
Brutal Regimen
Chavez contracted hepatitis C before the latest treatments were available. Now recovered, he helps others get hepatitis C as well as HIV treatment in the San Francisco Bay area. He took injections of interferon, an older drug, for almost a year to rid his body of the virus. It was a brutal regimen, he said, though it worked.
“It was terrible,” Chavez said. “I was up against it, so I had to do it, But if I had the choice today I wouldn’t.”
He and others may not have that choice.
Last year, Express Scripts stopped covering insulins and a diabetes injection made by Novo Nordisk A/S in favor of products from Eli Lilly & Co., AstraZeneca Plc and Bristol-Myers Squibb Co. (BMY) In the last four weeks, prescriptions of Lilly’s insulin Humalog are up 15 percent compared with the four weeks before Express Scripts’ change, while prescriptions of Novo’s Novolog are flat.
Comparing Drugs
Express Scripts and other pharmacy managers have since said that they’re ready to block other drugs from coverage.
“We will identify which drugs can be pitted against each other and make some really tough formulary decisions,” the company’s Chief Medical Officer Steven Miller said in a December interview.
In the U.K. and Europe, health regulators regularly weigh the benefit of drugs against their cost when deciding what the countries’ national health systems will pay for. Bristol-Myers stopped selling a diabetes drug in Germany last month after the government refused to meet its price, for example.
Obamacare Customer
Obamacare could have a similar effect as individuals begin to weigh the cost of insurance products, said Jami Rubin, an analyst with Goldman Sachs Group Inc. With the Affordable Care Act’s insurance expansion, millions of new customers in the law’s health care marketplaces will be picking and choosing among drug plans based on cost and coverage, instead of having their company pick a plan for them.
“What will society pay for a cure?,” said Rubin. “Is a
cure worth $1,000 a day?”
To contact the reporter on this story: Drew Armstrong in New York at darmstrong17@bloomberg.net
IDIX (3.75) CLF (36.49) MNTA (13.14) - near 52 week lows (eom).
Yet another case of big government bending the rules (or looking the other way) in favor of big business. It happens frequently (believe me, I know). There might even be a nice consultancy position in NJ for some future federal govt. retiree(s).
Revised View Enhances Provenge OS Data
http://www.onclive.com/web-exclusives/Revised-View-Enhances-Provenge-OS-Data
Anita T. Shaffer
Published Online: Thursday, April 19th, 2012
A further analysis of clinical trial data for sipuleucel-T (Provenge) suggests that the therapeutic prostate cancer vaccine may have delivered a greater overall survival (OS) benefit than previously described in the study that paved the way for its approval nearly two years ago, according to a leading researcher.
In fact, the analysis indicated that the survival benefit may be significantly higher than the 4.1-month advantage reported in the IMPACT study when the experiences of patients in the control arm who crossed over to a cryopreserved form of the vaccine are considered, said Leonard G. Gomella, MD, chairman of the Department of Urology and director of Clinical Affairs at the Kimmel Cancer Center, Thomas Jefferson University, in Philadelphia, Pennsylvania.
Gomella discussed his hypothesis at the 5th Annual Interdisciplinary Prostate Cancer Congress (IPCC) March 31 in New York City, for which he served as a program director. The research was presented at the 2012 Genitourinary Cancer Symposium sponsored by the American Society of Clinical Oncology (ASCO) in February and at the 2011 ASCO Annual Meeting.
Gomella’s comments come amid continuing controversy over sipuleucel-T, including a recent commentary in the Journal of the National Cancer Institute that maintained previously unpublished data cast doubt on the vaccine’s survival benefit partly because of factors involving patients in the placebo arm.
The FDA approved Provenge on April 29, 2010 for the treatment of asymptomatic or minimally symptomatic metastatic castrate-resistant, hormone-refractory prostate cancer based on clinical trial data demonstrating that patients who took the vaccine experienced a median OS of 25.8 months versus 21.7 months for those who received a placebo.
Sipuleucel-T is custom-manufactured for each patient from antigen-presenting cells that are harvested from the patient through the process of leukapheresis, then cultured to activate immunogenicity, and infused into the patient. The treatment course consists of three intravenous infusions.
In his analysis, Gomella looked more closely at participants in the control arms of three randomized, double-blind sipuleucel-T studies. Of 249 people in the control arms, 216 participants who experienced disease progression had the option of receiving APC8015F, an autologous immunotherapy with the same potency as sipuleucel-T that was made for each patient and cryopreserved at the time the placebo was prepared.
For the 155 patients from the control arm who received APC8015F, the median OS was 23.6 months from randomization and 20.0 months following disease progression, which compared favorably with the median OS in the sipuleucel-T arms of 25.4 months from randomization and 20.7 months after progression.
In contrast, the 61 participants from the control arm who experienced disease progression but did not cross over to APC8015F had a median OS of 12.7 months from randomization and 9.8 months following disease progression.
“The survival difference was dramatically different,” Gomella said during his IPCC presentation. “So in a way, the sipuleucel-T trials shot themselves in the foot because the frozen product was included. If you exclude the frozen product, you actually get a much more dramatic and a much more robust response of about 10 to 12 months.”
In an interview, Gomella added, “From my viewpoint, the benefit of sipuleucel-T has been understated because many of the patients who received the frozen product who were on the control arm actually enjoyed a longer survival, decreasing the difference between the control arm and the treatment arm.
“In fact, if you look at our analysis of the patients who received a frozen product on the control arm and those who did not receive it, there was a significant survival advantage to those patients who did receive the frozen product,” said Gomella. “It made the difference between the control arm and the actual treatment arm much closer. And if you take out those patients who did not receive the frozen product on the control arm, that survival difference actually approaches 10 to 11 months.”
Gomella’s analysis stands in sharp contrast to the contentions of Huber et al, who argue that previously unpublished trial data show worse OS in older versus younger patients in the placebo groups, and that the difference may stem from the study design.
Patients on placebo who were younger than age 65 experienced an 11-month median survival advantage when compared with those over age 65 (28.2 months vs 17.2 months, respectively), the authors said. They contend that the placebo intervention itself may have adversely affected older patients in the placebo arm and therefore enhanced the sipuleucel-T survival advantage.
“Because two-thirds of the cells harvested from placebo patients, but not from the sipuleucel-T arm, were frozen and not reinfused, a detrimental effect of this large repeated cell loss provides a potential alternative explanation for the survival ‘benefit,’” the authors said.
In his IPCC presentation, Gomella said researchers are debating the impact of extracting immune cells, but that a study pending publication indicates the “number of immune cells you pull out of the body with leukapheresis is clinically insignificant.”
Meanwhile, Dendreon Corporation, the Seattle, Washington, company that developed Provenge, is continuing to investigate the vaccine for patients with earlier-stage disease.
--------------------------------------------------------------------------------
Key Research
Gomella LG, Nabhan C, Whitmore JB, et al. Post-progression treatment with APC8015F may have prolonged survival of subjects in the control arm of sipuleucel-T phase III studies. Poster presented at: 2011 ASCO Annual Meeting; June 3-7, 2011; Chicago, IL. Abstract 4534.
Huber ML, Haynes L, Parker C, et al. Interdisciplinary critique of sipuleucel-T as immunotherapy in castration-resistant prostate cancer [published online ahead of print January 9, 2012]. J Natl Inst. 2012;104(4):273-279.
Kantoff PW, Higano CS, Shore ND, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363(5):411-422.
Nabhan C, Gomella LG, DeVries T, et al. An analysis to quantify the overall survival (OS) benefit of sipuleucel-T accounting for the crossover in the control arm of the IMPACT study. J Clin Oncol. 2012;30(suppl 5;abstract 144).
In the Pipeline: Immunotherapy Slows Childhood
((may be relevant to CLDX followers))
http://www.oncologyreport.com/news/top-news/single-view/in-the-pipeline-immunotherapy-slows-childhood-gliomas/7736eb7d1e.html
By: DIANA MAHONEY, Oncology Report Digital Network
04/04/12
CHICAGO – Immunotherapy with peptide vaccines may offer a much-needed therapeutic option for gliomas in children, which carry a poor prognosis despite current treatments.
In a pilot trial of subcutaneous vaccinations with peptides for glioma-associated antigen (GAA) epitopes in children who have been newly diagnosed with brain stem gliomas, cerebral high-grade gliomas, or recurrent gliomas, the immunotherapy was well tolerated and demonstrated immunologic and clinical activity, Dr. Ian F. Pollack reported April 2 at the annual meeting of the American Association for Cancer Research.
Based on significant experience with immunotherapy for adult gliomas, "we extended these insights to childhood gliomas – malignant astrocytomas of the brain stem and cerebral hemispheres and recurrent low-grade gliomas – based on our observations of their glioma-associated antigen expression profiles," Dr. Pollack explained during a press conference.
For the pilot study, Dr. Pollack, chief of pediatric neurosurgery at Children’s Hospital of Pittsburgh Brain Care Institute, and his colleagues have enrolled 27 human leukocyte antigen (HLA) A2–positive children to date, including 16 who are newly diagnosed with brain stem gliomas, 5 with newly diagnosed high-grade gliomas, and 6 with recurrent gliomas. The GAAs were EphA2, interleukin-13 receptor alpha 2 (IL-13RA2), and survivin, he said.
All of the children received eight courses of subcutaneous vaccinations with peptides for GAA epitopes emulsified in Montanide-ISA-51 every 3 weeks, along with intramuscular injections of the immunoadjuvant poly-ICLC, which promotes the infiltration of effector T cells into intracranial gliomas.
"Our primary end points were safety and T-cell response against vaccine-targeted [GAAs]," he said, noting that treatment response was assessed clinically and by MRI.
The preliminary results reported at the meeting are based on an interim analysis of 22 evaluable patients. To date, no non–central nervous system toxicities have limited the vaccine dosages, Dr. Pollack said. Of the 22 children, 4 showed signs of rapidly progressive disease, 14 had stable disease for more than 3 months, 3 had sustained partial responses, and 1 had prolonged disease-free status after surgery, he reported.
Symptomatic "pseudoprogression" – consisting of transient neurologic deterioration and tumor enlargement, followed by tumor regression and stabilization on decreasing steroid doses with sustained partial response – was observed in four of the children with brain stem glioma, said Dr. Pollack, who is also codirector of the University of Pittsburgh Cancer Institute’s brain tumor program.
Results of the ELISPOT (enzyme-linked immunosorbent spot) assay, which was completed in seven of the children, showed responses in six of them. Specifically, the investigators observed responses to IL-13RA2 in five cases, EphA2 in three cases, and survivin in three cases, Dr. Pollack said.
"Based on what we’ve seen so far, it seems that these kids are able to mount immune responses to the vaccine at high rates, possibly higher than we’ve seen in adult studies," likely because of their robust immune systems, he said in an interview.
The observation of immunologic and clinical response – particularly the evidence of tumor shrinkage in children with very high-risk tumors – "has been extremely encouraging and somewhat surprising," Dr. Pollack reported. "This is the first study of its type that examined peptide vaccine therapy for children with brain tumors like this."
The findings are especially notable because children with these tumors generally do not respond well to standard chemotherapy, he said, stressing that if further study validates the early findings, "immunotherapy may be a promising strategy to control tumor growth."
The study was funded by the National Institutes of Health. Dr. Pollack disclosed having no potential conflicts of interest.
In cancer science, many "discoveries" don't hold up
http://www.reuters.com/article/2012/03/28/us-science-cancer-idUSBRE82R12P20120328
Credit: Reuters/Sebastian Derungs
By Sharon Begley
NEW YORK | Wed Mar 28, 2012 2:09pm EDT
NEW YORK (Reuters) - A former researcher at Amgen Inc has found that many basic studies on cancer -- a high proportion of them from university labs -- are unreliable, with grim consequences for producing new medicines in the future.
During a decade as head of global cancer research at Amgen, C. Glenn Begley identified 53 "landmark" publications -- papers in top journals, from reputable labs -- for his team to reproduce. Begley sought to double-check the findings before trying to build on them for drug development.
Result: 47 of the 53 could not be replicated. He described his findings in a commentary piece published on Wednesday in the journal Nature.
"It was shocking," said Begley, now senior vice president of privately held biotechnology company TetraLogic, which develops cancer drugs. "These are the studies the pharmaceutical industry relies on to identify new targets for drug development. But if you're going to place a $1 million or $2 million or $5 million bet on an observation, you need to be sure it's true. As we tried to reproduce these papers we became convinced you can't take anything at face value."
The failure to win "the war on cancer" has been blamed on many factors, from the use of mouse models that are irrelevant to human cancers to risk-averse funding agencies. But recently a new culprit has emerged: too many basic scientific discoveries, done in animals or cells growing in lab dishes and meant to show the way to a new drug, are wrong.
Begley's experience echoes a report from scientists at Bayer AG last year. Neither group of researchers alleges fraud, nor would they identify the research they had tried to replicate.
But they and others fear the phenomenon is the product of a skewed system of incentives that has academics cutting corners to further their careers.
George Robertson of Dalhousie University in Nova Scotia previously worked at Merck on neurodegenerative diseases such as Parkinson's. While at Merck, he also found many academic studies that did not hold up.
"It drives people in industry crazy. Why are we seeing a collapse of the pharma and biotech industries? One possibility is that academia is not providing accurate findings," he said.
BELIEVE IT OR NOT
Over the last two decades, the most promising route to new cancer drugs has been one pioneered by the discoverers of Gleevec, the Novartis drug that targets a form of leukemia, and Herceptin, Genentech's breast-cancer drug. In each case, scientists discovered a genetic change that turned a normal cell into a malignant one. Those findings allowed them to develop a molecule that blocks the cancer-producing process.
This approach led to an explosion of claims of other potential "druggable" targets. Amgen tried to replicate the new papers before launching its own drug-discovery projects.
Scientists at Bayer did not have much more success. In a 2011 paper titled, "Believe it or not," they analyzed in-house projects that built on "exciting published data" from basic science studies. "Often, key data could not be reproduced," wrote Khusru Asadullah, vice president and head of target discovery at Bayer HealthCare in Berlin, and colleagues.
Of 47 cancer projects at Bayer during 2011, less than one-quarter could reproduce previously reported findings, despite the efforts of three or four scientists working full time for up to a year. Bayer dropped the projects.
Bayer and Amgen found that the prestige of a journal was no guarantee a paper would be solid. "The scientific community assumes that the claims in a preclinical study can be taken at face value," Begley and Lee Ellis of MD Anderson Cancer Center wrote in Nature. It assumes, too, that "the main message of the paper can be relied on ... Unfortunately, this is not always the case."
When the Amgen replication team of about 100 scientists could not confirm reported results, they contacted the authors. Those who cooperated discussed what might account for the inability of Amgen to confirm the results. Some let Amgen borrow antibodies and other materials used in the original study or even repeat experiments under the original authors' direction.
Some authors required the Amgen scientists sign a confidentiality agreement barring them from disclosing data at odds with the original findings. "The world will never know" which 47 studies -- many of them highly cited -- are apparently wrong, Begley said.
The most common response by the challenged scientists was: "you didn't do it right." Indeed, cancer biology is fiendishly complex, noted Phil Sharp, a cancer biologist and Nobel laureate at the Massachusetts Institute of Technology.
Even in the most rigorous studies, the results might be reproducible only in very specific conditions, Sharp explained: "A cancer cell might respond one way in one set of conditions and another way in different conditions. I think a lot of the variability can come from that."
THE BEST STORY
Other scientists worry that something less innocuous explains the lack of reproducibility.
Part way through his project to reproduce promising studies, Begley met for breakfast at a cancer conference with the lead scientist of one of the problematic studies.
"We went through the paper line by line, figure by figure," said Begley. "I explained that we re-did their experiment 50 times and never got their result. He said they'd done it six times and got this result once, but put it in the paper because it made the best story. It's very disillusioning."
Such selective publication is just one reason the scientific literature is peppered with incorrect results.
For one thing, basic science studies are rarely "blinded" the way clinical trials are. That is, researchers know which cell line or mouse got a treatment or had cancer. That can be a problem when data are subject to interpretation, as a researcher who is intellectually invested in a theory is more likely to interpret ambiguous evidence in its favor.
The problem goes beyond cancer.
On Tuesday, a committee of the National Academy of Sciences heard testimony that the number of scientific papers that had to be retracted increased more than tenfold over the last decade; the number of journal articles published rose only 44 percent.
Ferric Fang of the University of Washington, speaking to the panel, said he blamed a hypercompetitive academic environment that fosters poor science and even fraud, as too many researchers compete for diminishing funding.
"The surest ticket to getting a grant or job is getting published in a high-profile journal," said Fang. "This is an unhealthy belief that can lead a scientist to engage in sensationalism and sometimes even dishonest behavior."
The academic reward system discourages efforts to ensure a finding was not a fluke. Nor is there an incentive to verify someone else's discovery. As recently as the late 1990s, most potential cancer-drug targets were backed by 100 to 200 publications. Now each may have fewer than half a dozen.
"If you can write it up and get it published you're not even thinking of reproducibility," said Ken Kaitin, director of the Tufts Center for the Study of Drug Development. "You make an observation and move on. There is no incentive to find out it was wrong."
(Note: Amgen researcher C. Glenn Begley is not related to the author of this story, Sharon Begley)
Try Morningstar:
http://www.morningstar.com/earnings/SearchResults.aspx?k=MA&type=2
or Seeking Alpha:
http://seekingalpha.com/tag/transcripts
Capital-IQ has them as well but you need a subscription.
OT - the author of "Thinking Fast, Thinking Slow", a book I have seen discussed here, is on PBS' Charlie Rose tonight.
ISIS - They certainly have a pipeline, some cash, and a $850 million market cap, but the biggest question I have is that Stanley Crooke has been CEO of the company since January 1989 and their antisense technology and their 1,500 patents has not brought anything meaningful to market in those 23 years.
Here is a recent interview he gave discussing mipomersen:
http://www.forbes.com/sites/matthewherper/2012/01/11/isis-ceo-predicts-success-for-his-cholesterol-medicine-and-substantial-delays-for-regeneron-pfizer-and-amgen/?partner=yahootix
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CLDX -So, I don't understand why someone would key in on 110 when trying to come up with a fair valuation for CLDX and ignore 011. Doesn't make much sense to me.
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That is why I wrote "FWIW". Personally, I think most of the biotech analysts take the current stock price and add 20% if they like the stock or subtract 20% if they dislike it, and totally make up the rest of their assumptions to fit their target price.
CDX-011 has the near term important data from the 2b, Rindo is in a registrational P3 trial with data years off, which trial wall street is placing higher value on, I have no clue. As of Dec. 1, 2011, Jefferies was putting all the value on Rindo. I also have no clue why the share price doubled in Jan while I was doing my due diligence. I have yet to purchase a share, but I am interested.
On 60 Minutes tonight: "A Duke University Oncologist accused of manipulating data in a cancer trial".
CLDX - FWIW Jefferies & Co does not even include CDX-011 in their revenue forecasts, so poor results in the breast 2b might not hurt the share price that much. Hopefully the placebo crossover component in the CDX-011 2b will not hurt or confound the results.
Jefferies: "After applying a 25% risk-adjusted discount to reflect clinical/regulatory risks, we estimate 2026 rindopepimut sales of $465 million ($621 million unadjusted) based on market share of 70% in the EGFRvIII overexpressing segment and 19% in the overall GBM market. We estimate rindopepimut pivotal Phase III ACT-IV data to be available H2 2016 with BLA filing 2017, FDA approval and launch late 2017/early 2018. Potential accelerated approval driving a shorter time-tomarket is upside to our estimates. We have not included ex-U.S. rindopepimut sales or sales in other cancer indications in our estimates. We do not include sales estimates for the rest of Celldex’s pipeline given the early-mid development stage with additional data needed to better delineate clinical profile and outlook for each drug candidate."
CLDX - thanks Exwannabe, I was just trying to relay what Dr. Vahdat appeared to say at the Analyst Day. I do not know what they need to go further, but I believe she said "same and they are still in the ballgame". Obviously the better the results the better the chances going forward. If I remember correctly she said the data and the FDA will tell them which way to go into P3. They may proceed on some promising sub-group data. Few treatment choices with any positive effect on triple negative, so the hurdle is low.
With respect to EGFRvIII positive or negative having a worse OS prognosis, any thoughts for the Rindo P3?, that journal article threw me for a loop.
CLDX - Clark and Mcbio, for the future CDX-011 triple negative Phase III, Dr. Vahdat said in the Q&A at the January Analyst Day at around the 2 hour 20 minute mark the Phase III trial endpoint is still up in the air. And at the the 2 hour 43 minute mark she says that as long as the IIb shows data as good or better than MD choice the drug is still in the ballgame and it is all about designing the appropriate Phase III and getting the FDA to agree to design - pts should have multiple options and any result at or better than MD choice is good for triple negative given the poor prognosis. see webcast:
http://edge.media-server.com/m/p/639b475g/lan/en
Clark or Mcbio: With respect to the Phase III Rindopepimut (CDX-110) in Glioblastoma EGFRvIII+, 8 out of the 33 trial locations are in India - any worries that the FDA might wet their diapers about any potential trial protocol violations? I would guess that India might be worse than Eastern Europe in this respect.
http://clinicaltrials.gov/ct2/show/study/NCT01480479?term=Rindopepimut+%28CDX-110%29&rank=2&show_locs=Y#locn
Also, this recent journal article:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257186/#SD1
"Major results were as follows: 1) the presence of EGFRvIII in GBM tumors correlates with longer OS. The association of EGFRvIII/Ki67 of 20% or less, of EGFRvIII/normal PTEN, and of EGFRvIII/methylated MGMT identified subgroups of GBM patients with better prognosis; 2) EGFRvIII expression is reduced in GBM recurring after adjuvant radiotherapy and TMZ; and 3) EGFRvIII-positive GBM neurosphere cells are less resistant to TMZ than their EGFRvIII-negative counterparts. Our findings on the prognostic significance of EGFRvIII in GBM diverge from previous studies, where this variant was found either to be unrelated to the patients' outcome [6,11,12,16–20] or to be associated with shorter survival (Table W5) [10,14]."
So if I am reading this correctly they are saying that EGFRvIII positive status leads to longer survival which is completely the opposite of what CLDX/Dr. Sampson have claimed that being EGFRvIII positive is a highly poor prognostic factor for survival. I do not know enough about the science to judge who is right or if this was just an oddball journal article.
Novartis Q4 profit halves to $1.2B on charges
Swiss drug maker Novartis sees Q4 profit down 47 percent to $1.2B on charges
By Frank Jordans, Associated Press | Associated Press
NVS 54.18 -1.69
DAVOS, Switzerland (AP) -- Swiss drug maker Novartis AG reported a 47 percent drop in its fourth-quarter net profit Wednesday, citing a slate of exceptional costs from the ending of clinical trials to manufacturing problems and layoffs.
The Basel-based company said its net profit reached $1.21 billion in the fourth quarter, compared with $2.32 billion in the same period in 2010. Sales rose four percent to $14.78 billion in the Oct.-Dec. period.
"We experienced some disappointments in the fourth quarter, with Tekturna/Rasilez and with the need to improve our quality standards at some manufacturing sites," Chief Executive Joseph Jimenez said in a statement.
Novartis recently halted a clinical trial into wider uses of the hypertension drug Tekturna, which is known as Rasilez outside the United States, after it was found to cause increased complications in patients already taking other common hypertension drugs.
The company said it took an exceptional charge of $900 million in the fourth quarter as a result of the trial ending.
Two other experimental drugs were also dropped, leading to one-off charges of $160 million in the fourth quarter.
Manufacturing problems led the company to recall several over-the-counter drugs from the U.S. market earlier this month. The company closed the Lincoln, Nebraska, facility where the products were manufactured and took a charge of $115 million for the temporary production halt.
Novartis said it would also book charges of $288 million for over 2,000 job cuts announced last year. Many of those were in the United States, where the company expects to see a sharp dip in sales with the expiry of another hypertension drug, Diovan.
"I am quite bullish on the future growth prospects for the company once we get Diovan out of the base," said Jimenez.
In a conference call, Jimenez told reporters that he didn't expect any further job cuts in 2012 "unless conditions change."
The results were in line with analyst expectations, but shares fell 2.5 percent to 50.70 Swiss francs ($54.58) on the Zurich exchange as traders focused on the company's cautious outlook for 2012.
"We consider the current results to be very strong, but the outlook particularly for 2012 will likely disappoint investors," Zuercher Kantonalbank said in an analyst note.
Novartis received 19 regulatory approvals worldwide in 2011, including 15 for new drugs.
Jimenez said his company supported a European medicines agency investigation into its multiple sclerosis drug Gilenya, following the death of one patient.
Gilenya contributed $494 million to sales results last year.
"We are confident that Gilenya will continue to be a growth driver," said Jimenez.
For the full year 2011, Novartis reported a net profit of $9.25 billion, down seven percent from $9.97 billion the previous year.
http://finance.yahoo.com/news/Novartis-Q4-profit-halves-1-apf-3727247394.html?x=0
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In short, your definition of biotech is evidently narrower than mine.
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Yes, I differentiate between large pharmaceutical companies and biotechnology companies (as does S&P, various stock indices and ETFs, etc.).
MNTA is in my view a biotechnology company and is included in the following biotechnology industry listing:
http://biz.yahoo.com/ic/515_cl_pub.html
ABT, PFE, NVS, AGN and PKI are in my view large pharma or medical device companies:
http://biz.yahoo.com/ic/510_cl_pub.html (although the Yahoo yahoos messed up their listing including a few pink sheet stocks as Major Drug Mfgs., but you get the idea) or
http://biz.yahoo.com/ic/520_cl_pub.html
In my view MON is an agricultural products company that utilizes biotechnology methods to develop some of its agricultural products.
The following article discusses some of the managerial and structural differences between big pharma and biotech:
http://www.heritageleaders.com/newsdocs/1a.pdf
So I take it that you do not currently see any “Biotech Values” companies (as traditionally categorized, in my view) worthy of your investment dollars that are not large pharma companies (other than MNTA, a company you know I like and feel you did excellent research on)? I only bring this up because you recently mentioned your My Stocks list and I only noticed MNTA as what many would consider a traditional biotech holding and in recent years rarely see you post about a traditional biotechnology company that you actually liked as an investment. Most of the other posters on your board appear to be investors in traditional biotechnology companies. I was just curious and it’s absolutely fine with me if you don’t currently own another traditional biotech. After all there are over 10,000 other US publicly traded non-biotech companies to choose from and the world’s financial markets currently appear riskier and investors more risk adverse than normal.
Happy New Year
From the iBox of this board:
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Biotech Values is a forum for discussing all facets of biotech investing with an emphasis on fundamental analysis and avoiding scams.
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Yet in your over 40,000 posts here on Biotech Values you have only identified 1 biotech stock for your current portfolio. Not saying I don't like some you your stock picks below, because I do and own a few of them (this is the 1st time I have seen your stock list, and have in the past met with Sr. Mgt. with 2 of them, ie. NVS and HES, as part of my work), and I am not saying that you are not highly knowledgeable in the biotech arena, because you clearly are, but with all the time you spend here, I would have thought you might have identified more than one "Biotech Value". I am not being at all confrontational, just curious to see if you identified any other "Biotech Values"?
Happy New Year
http://investorshub.advfn.com/boards/profiles.aspx?user=14742
Momenta Pharmaceuticals, Inc.
Abbott Laboratories
Allergan
BHP Billiton plc
Core Laboratories N.V.
Cliffs Natural Resources Inc.
Cubic Corp.
Deere & Co.
Hess Corporation
Heinz
3M Co.
Monsanto Co.
Novartis
PerkinElmer Incorporated
Pfizer, Inc.
Plum Creek Timber
Procter & Gamble Co
Royal Dutch Shell plc
Vale S. A.
Quote: "I realize that this is an extraordinarily complex and controversial issue, but given the stratospheric cost and the low median survival benefit, I just can't see it."
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Maybe you will see "it" a bit better when you realize that Provenge is one of only four drugs ever approved by the FDA to extend median lives by 4 months or more for any form of metastatic cancer. The three other drugs that have ever shown a 4 month or better survival benefit in any form of metastatic cancer were: 1) Avastin, 2) Herceptin, and 3) Altima. Please note that survival is the FDA's "gold standard" for measuring cancer trial outcomes (and is not subject to the high noise or ambiguity of results shown by other clinical outcomes like progression for example). Of course, since this is a median figure, some patients do much better than 4 months. Also, there was a 70% placebo cross-over rate to active treatment, so it is very likely that the demonstrated survival benefit was mutted. The treatment benefit is accomplished with a highly favorable side effect profile and the entire course of therapy is a short 1 month, thereby freeing patients to pursue other courses of treatment. Finally, CMS left the door wide open today to expand the reimbursed Provenge label or patient population should future robust evidence develop.
<<"Base model, DCF analysis support $19 price objective
Our base model and $19 discounted cash flow-based PO assume no competition on Lovenox until 2013 and a generic Copaxone launch in mid-2014 (Teva’s patent expiry), with MNTA alone through 2016, which we believe is reasonable.">>
This statement from BoA is especially idiotic, as MNTA's cash balance alone under such a scenario would probably exceed $19.
Judging by the stock price movement and volume over the last few minutes, someone must have liked what they heard