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Sanofi's rumored buyout plans inspire guessing game
By John Carroll
Frankly, I think that Viehbacher had a group of large cap biotech names in his personal account and was looking to sell them on strengh. If he was looking to buy one why would he want the pricetag to go up before he put in a bid.
The scuttlebutt from Bloomberg late last week about Sanofi-Aventis' interest in acquiring an unidentified drug developer in the pricey neighborhood of $20 billion has triggered a fevered new game of name-the-target.
For its part, the Wall Street Journal's Michael Corkery ran a slate of five potential developers that fit the general profile: Genzyme ($13 billion market cap); Biogen Idec ($13 billion); Celgene ($23 billion); Gilead Sciences and Amgen. With a market cap of $50 billion, though, Amgen would seem to be a far larger company than Sanofi would want to swallow right now.
For its part, Reuters helped stir the pot of market rumors with its own sources discussing one or two deals worth around $15 billion each. That helped spur shares of Biogen, Genzyme and Allergan, another hotly rumored target. Of course, in the biopharma business, M&A deals are always on the table in one fashion or another.
"In big pharma, everybody is looking at everything and they all have big departments looking at possible acquisitions," Raymond James analyst Thierry Verrecchia told Reuters.
TheStreet's Adam Feuerstein, meanwhile, doesn't think any of the big biotech companies are on Sanofi's list of potential takeover targets. He likes Allergan as the company most likely to help Sanofi diversify.
"I think this is all hogwash," counters Matthew Herper at Forbes. "I don't know what (Sanofi CEO Chris) Viehbacher is planning, but I've interviewed him about mergers several times since he took over in 2008, and a deal of the size and scope we're speculating is completely within the realm of what he's previously discussed. And a biotech certainly could make sense for Sanofi
I worked for Victor Posner from 1979 to 1982
He was as nasty as he was intelligent. His family was also very mixed up. I used to drive his daughter around when the cheuffer or body guard was busy. She died in March but I didn't know it until I read it in the Wall St Jounal. She was mixed up but I felt bad for her. From the few times I met him, I believed her son Brett seemed like one of the better adjusted children but he looks like he has had his problems also. She had a daughter that I never met but it appears she either died of an overdose or suicide in the 1990's.
Little Dog, Large Estate
Chihuahua at Center of Fight Over Posner Heiress's
By MARK MAREMONT And LESLIE SCISM
Her name is Conchita, a thin, spa-loving, diamond-draped heiress, and she's at the center of one of America's nastiest estate battles.
She is also a dog—a chihuahua who was the favorite of the late Miami heiress Gail Posner, a daughter of the corporate takeover artist Victor Posner.
When Ms. Posner died in March at age 67, Conchita and two other dogs inherited the right to live in her seven-bedroom, $8.3 million Miami Beach mansion, their comfort ensured by a $3 million trust fund.
The canines weren't the only ones who benefited from Ms. Posner's munificence. Seven of her bodyguards, housekeepers and other personal aides were left a total of $26 million under her will, and some also were allowed to live, rent-free, in the mansion to care for the dogs.
Now, in an attempt to revoke the will, Ms. Posner's only living child, Bret Carr, has filed a lawsuit against a bevy of his mother's former staff members and advisers alleging a dark intrigue.
Household aides, he claims, drugged his sick mother with pain medications and conspired to steal her assets by inducing her to change her will and trust arrangements in 2008. Others, including his mother's trust attorney, he alleges, used their influence to bend her wishes. Mr. Carr, who was bequeathed a relatively paltry $1 million in his mother's will, makes the claims in a lawsuit filed last week in probate court in Miami-Dade County.
Among Mr. Carr's claims is that the aides directed a "deeply disturbed" Ms. Posner to hire a publicist to promote Conchita as "one of the world's most spoiled dogs"—complete with a four-season wardrobe, full-time staff and diamond jewelry. Mr. Carr's lawyer, Bruce Katzen, says he believes the publicity campaign was part of a "ruse" to explain why a large trust fund was needed to care for the dogs.
Bret Carr
Bret Carr, Gail Posner's son, is disputing the will, alleging intrigue.
.It's too early to predict the outcome of the case. But Ray Madoff, a Boston College law professor and co-author of an estate-planning guide, says wills that leave little or nothing to legitimate heirs but millions to caretakers are usually thrown out by courts, as likely to have been written with "undue influence" by the caretakers.
The case has echoes of the late Leona Helmsley. In 2007, the New York real estate magnate left a $12 million trust fund to Trouble, her pet Maltese. A judge later cut that down to $2 million and directed the rest go to charity. Under the terms of Ms. Posner's trust, the mansion is to be sold after her dogs die, and the proceeds donated to charity.
But the Posner dispute has a grimmer backdrop. The clan has long been haunted by drug and alcohol addiction, claims of sexual abuse allegedly committed by Victor Posner and prior legal battles over the spoils of Mr. Posner's 1980s-era checkered career.
A master of the hostile takeover who became one of America's highest-paid executives, Mr. Posner pleaded no contest to tax evasion charges in 1987 and was later barred from involvement with public companies.
Mr. Carr, a Hollywood screenwriter and filmmaker, has his own troubled past. He was arrested in 1992, charged with counterfeiting traveler's checks. He received probation, and told The Wall Street Journal in 1994 that his grandfather severed all contact with him after the incident.
Documents
See Gail Posner's trust (42-page PDF)
Read Bret Carr's lawsuit
.Mr. Carr also names as a defendant BNY Mellon, which helped oversee a trust that Mr. Posner established for his daughter in 1965. According to the complaint, the trust at one point was worth more than $100 million. It was terminated in 2008 and its remaining assets distributed to Ms. Posner.
A BNY Mellon spokeswoman said the bank "acted appropriately" as trustee, and plans to "vigorously defend" against the lawsuit. Martin Rosen, an attorney who was a trustee for the trust until shortly after Victor Posner's death in 2002, said that it held "in the area of $6 million" when he left his post and "never had $100 million or anything like it."
Mr. Carr's relationship with his mother is portrayed in the lawsuit as rocky, but he says they had a close relationship during "the sober phases of her life." He also says she variously told him that he would inherit her entire estate; half of her inheritance from Victor Posner; and a house next door to hers, also owned by the family.
According to the complaint, Ms. Posner had a "long history of paranoia" and was concerned about her security. She eventually hired several bodyguards. The lawsuit contends that these people, along with other domestic staff, allegedly conspired to isolate Ms. Posner from family members, proceeding to "brainwash" her into believing her son was out to kill her and only the staff could be trusted.
Ms. Posner allegedly told her son she was "being kidnapped by the staff who was trying to kill her."
Around this same period, Ms. Posner began publicizing her pampered pooch. In an interview with the Miami Herald in 2007, she said the dog's most precious possession was a Cartier necklace worth $15,000, but the dog choked on it and was refusing to wear it.
"Conchita is the only girl I know who doesn't consider diamonds her best friend," Ms. Posner was quoted as saying.
In a 2009 interview with a blogger for browardpalmbeach.com, Ms. Posner said Conchita typically accompanied her on lunch dates and then shopping. Ms. Posner said she at one point considered getting the dog her own Range Rover, for transportation to the animal's weekly spa appointments for manicures and pedicures, but Ms. Posner decided to get herself a new car and gave the dog her gold Cadillac Escalade, she told the blogger.
In 2008, already sick with cancer, Ms. Posner executed a new will and trust agreement, overseen by a New York lawyer, Sanford Schlesinger, who is named a defendant in the suit. Under the new arrangement, according to the lawsuit, Ms. Posner left $10 million to one bodyguard, $5 million to another and $2 million to a personal trainer.
Conchita
.Journal Communitydiscuss..“ As a true dog lover, I understand her (and Leona's) decision. They are my BEST friends. ”
.—Laurie Holasek.
A housekeeper and personal assistant, Queen Elizabeth Beckford, would receive $5 million if she agreed to care for Conchita and two other dogs, April Maria and Lucia, at the mansion "with the same degree of care" they received while Ms. Posner was alive, according to the trust established to distribute Ms. Posner's assets. Ms. Beckford also was given permission to live, rent-free, in Ms. Posner's Miami Beach mansion, along with her mother. Ms. Beckford's daughter, another assistant, received $1 million.
Reached at the Miami Beach mansion, Ms. Beckford declined to comment, saying "everything is confidential" before hanging up. Hernando Quintero, the bodyguard who inherited $10 million, could not be reached for comment. Orion Sewell, who was bequeathed $5 million, declined to comment.
An attorney representing Mr. Schlesinger and Gail Posner's trust declined to comment.
Ms. Posner left the remainder of her estate to charity, with one-quarter directed to animal shelters and the rest to breast cancer and suicide-prevention causes. She also left another request: that the canine-care staff also look after her pet turtles.
—James Oberman contributed to this article.
Write to Mark Maremont at mark.maremont@wsj.com and Leslie Scism at leslie.scism@wsj.com
Copyright 2009 Dow Jones & Company, Inc. All Rights Reserved
actually he cut the rating because his firm wasn't hired to do the strategic alternatives search.
There are funds that want to put money in but it is over 65 percent owned by nordic Biosciences a private equity fund.
They have a drug that is strontium malonate which is a pill. There is a drug in Europe called protelos, strontium ranolate, which is a sachet doing over 300 million a year and growing.
they have been given guidamce in Europe that they only need a tiny study in europe to get their drug approved over there, probably in 2012. Look for the press release. With their better bioavailablitly and oral delivery, there is no reason to think that they couldn't take at least a 100 million in revs away from protelos, probably a lot more.
In the US they would need to run probably a 100 million dollar phase 3 trial so they need a partner or would need to sell the company.
So you look at the 15 million market cap as a cheap valuation for the value of the product based on a european approval, and the US deal as a lottery ticket. You would need to look at this as a private company because you can't trade it.
That is all, I own it, you looked at it, and you can do what you want with it.
If you want to look at the way the drug works watch the video
http://www.protelos.com/Pro/Osteoporosis/Protelos/Protelos.aspx?id=2163
The problem with bisposhonates is that they shut off bone resorption in the 80 percent range. Denosumab shuts it off at an even higher percentage. Neither drug increases bone reformation. This drug does that.
THE MARKET FOR DISEASE-MODIFYING OSTEOARTHRITIS DRUGS WILL EXPERIENCE EXPONENTIAL GROWTH, INCREASING FROM $477 MILLION IN 2007 TO NEARLY $3.8 BILLION IN 2017Extensive Need for Disease-Modifying Agents Creates Significant Opportunity for Drug Developers, According to a New Report from Decision Resources
I thought I would mention this because of the recent failure of Pfizers' Tanezumab
October 8, 2008-Waltham, Mass. - Decision Resources, one of the world's leading research and advisory firms for pharmaceutical and healthcare issues, finds that, despite the anticipated approval of only one disease-modifying therapy over the next decade, the market for disease-modifying osteoarthritis drugs will experience exponential growth, increasing from $477 million in 2007 to nearly $3.8 billion in 2017.
The new Pharmacor report entitled Osteoarthritis: Disease-Modifying Therapies, finds that, following its anticipated approval in 2011, the uptake of Servier's Protelos,OLGX has a drug that works the same way as servier's Protelos as well as off-label use of Novartis/Nordic Bioscience/Emisphere Technologies' SMC-021 for its disease-modifying potential, will drive the tremendous growth of the osteoarthritis drug market through 2017. Market growth will also be fueled by increasing prevalence of osteoarthritis and an increase in drug-treatment rates in the United States and Europe as patients switch from over-the-counter agents with unproven efficacy to new prescription drugs that promise to slow structural progression and improve symptoms of the disease. According to the report, there are 37 million patients diagnosed with osteoarthritis in the United States, France, Germany, Italy, Spain, the United Kingdom and Japan.
The report finds that, owing to the need for disease-modifying drugs, significant opportunity remains for developers of osteoarthritis drugs. Additionally, although some studies have suggested that glucosamine, chondroitin sulfate, diacerein and avocado soybean unsaponifiables may slow the structural progression of osteoarthritis, these agents are not widely accepted as disease-modifying therapies.
"Because of the controversy surrounding the efficacy of agents such as glucosamine or chondroitin sulfate, physicians' responses varied widely in regard to prescribing or recommending these agents to osteoarthritis patients," said Amy Whiting, Ph.D., analyst at Decision Resources. "Although some rheumatologists might recommend glucosamine or chondroitin sulfate to their patients, interviewed experts say that the benefit of these agents has never been proven."
About Decision Resources
Decision Resources (www.decisionresources.com) is a world leader in market research publications, advisory services and consulting designed to help clients shape strategy, allocate resources and master their chosen markets. Decision Resources is a Decision Resources, Inc. company.
About Decision Resources, Inc.
Decision Resources, Inc. is a cohesive portfolio of companies that offers best-in-class, high-value information and insights on important sectors of the healthcare industry. Clients rely on this analysis and data to make informed decisions. Please visit Decision Resources, Inc. at www.DecisionResourcesInc.com.
###
they were running out of money and did a financing with an a--hole priced at 12 cents and he is killing the stock.
The Future of Banking.............
it is pretty amazing that what brought the economies to the brink a couple of years ago was that the big banks were to big to fail.
What this writer is bringing out is that the new regs will for the small banks to not be competitive so big banks will only get bigger.
the mains street media, nor has the financial press or outlets, brought these points out.
what am I missing?
Good decision, IMO. PFE’s share price not only values the pipeline at close to zero, but also discounts the continuing EPS gain from post-merger cost-cutting. All told, the Wyeth acquisition will boost PFE’s profitability by more than a Lipitor-sized drug would be able to do
What is pfizer going to earn in 2010, 2011, and 2012.
How do they make of for 12 billion in lipitor sales with a gross margin of 85 to 90 percent.
why are you giving him info on fundamentals and he is looking at technicals and the stock is broken
you could be right
but if you sell you have to look at what the price is now and whether you can sell at that price, without worrying about whether it is a gain or a loss.
external factors like gain or loss shouldn't enter in the equation, but it does.
Cypress Plummets on $365M
BioLineRx Schizophrenia Deal
By Donna Young
so he made this deal knowing the street would not like him making a deal that would cost him twice as much on development than he has in the bank. He knows better than everyone else especially his shareholders...Sounds like he could run for president.
Cypress Bioscience Inc. is paying Israeli biotech BioLineRx
Ltd. $30 million up front and potentially $335 million
in milestones for the exclusive North American development
and commercialization rights to its antipsychotic
compound CYP-1020 (previously BL-1020), which currently
is under investigation to treat schizophrenia.
But Cypress investors decided the alliance was a bad
move, sending shares of the San Diego-based firm (NASDAQ:
CYPB) spiraling 37.8 percent Monday, or $1.64, to
close at $2.70.
CEO Jay Kranzler said that although he was “disappointed”
in the market’s reaction to the deal, it was “not
surprising.”
“We anticipated that this was the likely reaction because many of our holders now are really focused on the
commercial side of our business and our transitioning that
to profitability, or selling it and realizing a return based on
that,” Kranzler told BioWorld Today.But Cypress’ management, he said, “realized over time
that that was not the best way of recognizing value for our
investors.”
Kranzler insisted that the firm’s real value was based
on its assets in expertise, which he said was a “longer-term
play” that required Cypress to get back into clinical development
of central nervous system (CNS) therapies, “an area
in which we have historically excelled.”
The company, he said, has experience “acknowledged
throughout the industry” with “complex” CNS drugs, specifically
in the psychiatric and chronic pain areas, which
“require some creativity rather than just following paths
that are already very well established.”
Kranzler said CYP-1020, a first-in-class GABA-enhanced
antipsychotic that combines dopamine antagonism with
GABAergic activity, “fits well” into the firm’s CNS portfolio.
He noted that Cypress currently co-promotes its
fibromyalgia drug Savella (milnacipran) in the U.S. with
partner New York-based Forest Laboratories Inc. under a
2004 deal. (See BioWorld Today, Jan. 12, 2004.)
The same management team that got Savella “successfully”
approved last year is going to lead the clinical development
program for CYP-1020, Kranzler noted. (See
BioWorld Today, Jan. 2, 2008, and Jan. 16, 2009.)
But Kranzler lamented that the “strength” of the development
and regulatory expertise gained from the Savella
experience has gone mostly unleveraged due to the company
over the past two years transitioning to and focusing
on the commercial side of that drug.
But the BioLineRx deal for CYP-1020, he declared, has
restored Cypress’ primary focus to R&D, “where we have
successfully demonstrated leadership, creativity and a
competitive advantage.”
Kranzler said he expected CYP-1020 to be a “gamechanger”
in the psychiatric drug space because of its ability
to improve cognition in patients with schizophrenia.
“This is not a drug that would compete with all of the
other antipsychotics for market share,” he said. “This is a
drug that would be the one and only antipsychotic that has
an improved cognition, which we believe would lead to its
use as a first-line treatment in many, if not most, patients.”
Michael Hufford, vice president of clinical development
at Cypress, said there is a “staggering unmet need” for
drugs to improve cognitive dysfunction in schizophrenia.
“These are patients for whom one of the greatest predictors
for long-term outcome is the cognitive dysfunction,”
he said.
Results of BioLineRx’s Phase IIb EAGLE study demonstrated
that CYP-1020 at the 20-mg to 30-mg dosage range
exhibited clinically relevant and statistically significant
improvement on the cognition endpoint assessed using
the Brief Assessment of Cognition in Schizophrenia (BACS)
neuropsychological test battery.
CYP-1020 was superior to both risperidone and placebo
at endpoint on the BACS total score, with a “p” value of
0.027 for both.
There were positive trends in all subsets within the
BACS, according to the firms.
The results also showed that CYP-1020 was effective as
a treatment for the other symptoms of acute schizophrenia
exacerbation, as measured by the Positive and Negative
Symptom Scale (PANSS).
The incidence of serious adverse events was low in the
CYP-1020 group compared with risperidone and placebo,
with discontinuations due to adverse events similar in the
CYP-1020 and placebo groups but higher in the risperidone
group.
Recent results from an extension trial showed that
patients receiving CYP-1020 20-mg to 30-mg per day
dosage for six additional weeks maintained the improvements
on the PANSS and clinical global impression scales
that had been observed after the initial six weeks of treatment
and showed continuing improvement in cognitive
function as assessed by the BACS. The 12-weeks of treatment
were not associated with any increased toxicities,
BioLineRx said.
Kranzler said the “somewhat surprising” CYP-1020
results reported last year on the cognitive endpoint was
what peaked Cypress’ interest in the drug and “started in
earnest” the discussions with BioLineRx.
Under the CYP-1020 deal, Jerusalem-based BioLineRx
stands to potentially gain up to $160 million in clinical and
regulatory milestones, $85 million tied to the commercialization
of the compound, and $90 million for the approval
of other indications in the U.S. or the approval of any indication,
including schizophrenia, in Canada or Mexico.
BioLineRx has retained the rest-of-world rights, which
the firm noted was about 50 percent of the global psychiatric
drug market.
Under the BioLineRx deal, Cypress will manage and
finance all future North American development of CYP-
1020, including the additional clinical trials required for
obtaining FDA approval, and will be responsible for filing
all regulatory applications.
The agreement also permits BioLineRx to use all regulatory
data produced by Cypress, in consideration for the
future repayment to the California firm of a portion of the
related costs, for regulatory applications outside of North
America.
Kranzler said Cypress has not decided whether it will
take CYP-1020 directly into a pivotal trial or do a more elaborate
and longer Phase II trial.
“What matters is to make sure you get it right and get
the drug approved,” he said. ¦
Jonathan Aschoff, Ph.D., 212-702-6652
aschoffj@bmur.com
2010 Revenue Is NOT the Story Here – Buy This Dip
Buy
Target Price:$65
Investment Summary
§Dendreon shares have traded have off substantially even compared to pre-approval levels, and we contend that way too much focus has been placed upon 2010 revenue numbers. For example, unlike Auxilium (AUXL $25.40, Sell), Dendreon launched with a 10% capacity, a deliberately controlled inflow of patients, treats a deadly disease, and will not be subject to the same reimbursement headwinds.
§This has resulted in substantial patient waiting lists for Provenge at the more than 40 of the 50 centers that are treating patients. Make no mistake – demand is high. The 50 centers have been told that they can only treat 2-3 patients per month per center, but demand is clearly exceeding that.
§The remaining 75% of Dendreon’s New Jersey capacity has been built out and is now going through validation, and we expect the full New Jersey facility to be approved for use early next year. The New Jersey facility represents only 40% of total U.S. capacity, with the remaining 60% coming on line at YE11.
§Some bears claim that nobody has been reimbursed for Provenge, but with only 55 days since approval, and an expected receipt of reimbursement 60-90 days after treatment, there should be no one that has yet received reimbursement. This bear claim is absolutely meaningless. We fully expect all the big insurers to cover the cost of Provenge, as it treats a life-threatening disease and is a rather high-profile therapy in the public eye.
§We have adjusted our revenue forecast for 2010 and 2011 to $65 million and $402 million, which was revised down from our previous estimates of $93 million and $430 million, respectively. Our revision only reflects capacity constraints within the first 12 months of launch that we failed to take into full account initially. These adjustments have absolutely no impact on the back half of 2011 or thereafter.
Valuation. Our target price is derived by applying a multiple of 40 and discount rate of 15% to our fully taxed 2013 EPS estimate of $2.36. This price target is based on a discount rate that would be expected to decrease upon an event as meaningfully risk reducing as FDA approval.
Risks. Risks to the achievement of our target price include the following: (1) market penetration of Provenge; (2) regulatory approval of Provenge; (3) business development; and (4) high stock price volatility
ariad intends on recruiting patients for their trial that have failed at least two other tki's. They will have a predefined subgroup of t315i mutation patients. They do not intend on running a separate t315i mutation study
MS Drug's Epic Journey From Folklore to Lab
Research Into Ancient Chinese Fungus That Propagates Inside Insects Yields Potential Relief for Multiple Sclerosis
http://online.wsj.com/article/SB10001424052748704256304575320714138159240.html#printMode
By PETER LANDERS
For centuries Chinese medicine has seen restorative properties in an Asian fungus that invades and destroys insects. Now a drug drawing on that age-old lore is poised to become an important new treatment for multiple sclerosis.
Natural Healing
View Interactive
Nature was the first source of medicines to treat human disease and remains an important one. See some of the most successful commercial medicines derived from natural products.
More photos and interactive graphics A Food and Drug Administration panel unanimously recommended this month that the drug called fingolimod be approved as the first oral medicine for MS, an often-debilitating disease in which the body's own immune system attacks a fatty substance protecting nerve fibers. The drug, assuming it gets final FDA approval, would significantly expand the treatment options for the hundreds of thousands of Americans with MS.
Nature was the first source of medicines to treat human disease and remains an important one. The Japanese scientists who discovered fingolimod added their names to a list that goes back to the European chemists who derived aspirin from a substance in willow bark and Alexander Fleming, who found that a fungus produced a bacteria-killing substance called penicillin.
Fingolimod comes from an idea hatched a quarter-century ago by Tetsuro Fujita, a Kyoto University pharmacology professor who had investigated bitter plants used in traditional Asian medicine. A wonder drug at the time was cyclosporin, which helps tamp down the immune system in transplant patients to reduce the risk of organ rejection. The chemical cyclosporin is derived from a fungus, first isolated from soil samples, that uses the substance to attack other fungi.
Novartis
Researchers in Japan and at Novartis turned a fungus that is deadly to cicadas into a new MS drug.
Dr. Fujita says he reasoned that an even more powerful immunosuppressant chemical ought to be present in a group of Asian fungi known in Chinese and Japanese as "winter-insect-summer-plants." These fungi attack insects in the winter with their chemical arsenal. By summertime, the insect is dead and its corpse has been transformed into a vessel for the blooming fungus. Ironically, the same properties that make the chemical deadly in the insect world may also have a helpful side for people suffering from certain autoimmune diseases, in which an overactive immune-system response causes the body to attack its own cells.
Dr. Fujita assembled a team from his university and two Japanese companies to sift through the various fungal products. They found a potent immunosuppressant in a particular kind of winter-insect-summer-plant, called Isaria sinclairii. This fungus victimizes a particular type of cicada found in East Asia, using it as a host in which to propagate. Chinese herbal medicine had long identified Isaria sinclairii as a source of "eternal youth" along with ginseng and deer antlers.
The immunosuppressant isolated from the fungus by the Japanese team was too toxic to give to humans. They needed to tweak it chemically. "Medicine and poison—they're two edges of the sword," says the 79-year-old Dr. Fujita by phone from his Kyoto home.
View Full Image
Michael W./Mushroom Observer
Nowadays, scientists generally rely on test-tube results for initial screening of experimental pharmaceutical drugs. But the Japanese group tried out all its promising drug candidates in rats, giving them skin transplants and seeing how long they survived after the resultant organ rejection. The molecule later named fingolimod proved to be the standout, significantly prolonging survival due to its immunosuppressant effect.
In 1997, Novartis AG's then-chief executive, Daniel Vasella, flew to Japan to seal a deal under which Novartis licensed the U.S. and European rights to the drug from Yoshitomi Pharmaceutical Industries (now part of Mitsubishi Tanabe Pharma Corp.).
After tests, Switzerland-based Novartis dropped the idea of using the medicine for transplant patients because it was no more effective than existing agents. But the company discovered that fingolimod had a powerful effect in multiple sclerosis, reducing the number of relapses in which patients may experience vision problems, fatigue, numbness and other symptoms. Trials in thousands of patients followed.
The FDA, which is expected to make a decision about fingolimod by September, doesn't have to follow the advice of the expert panel but usually does. In a separate report, FDA staff came to a similar conclusion as the panel. Fingolimod has side effects that include reduced heart rate on the first day of dosing and, in rare cases, swelling in the eye, but the benefits of the drug outweighed the risks, the staff report said.
View Full Image
Jinsuk Kim
Novartis's head of global development, Trevor Mundel, says fingolimod doesn't destroy immune cells that are attacking the protective covering around nerve fibers. Instead, the drug works to prevent the immune cells from overreacting in the first place, inducing them to "stay in their home base," he says. The benefit of this approach, he says, is that it can be reversed more quickly in the event of problems with the drug.
Novartis, taking a hint from products such as fingolimod, has set up a research unit that focuses on finding new drugs from traditional Chinese medicines. "We're well aware that there are some very interesting compounds that reside in that area," Dr. Mundel says.
Write to Peter Landers at peter.landers@wsj.com
Thailand to test Mahidol-developed dengue vaccine prototype
they had successful animal studies.
Thai researchers have planned to test a dengue fever vaccine on 3,000-5,000 human volunteers within the next three years after having successfully conducted tests on animals and a small group of human volunteers, Thai News Agency reported Sunday.
Dengue fever is an infectious disease carried by mosquitoes and caused by any of four related dengue viruses. A patient develops high fever, rash, headaches and severe muscle and joint pains.
Prof. Suthee Yoksan, director of Mahidol University's Vaccine Development Center for Research said the center has developed a vaccine which may help prevent infection from all four strains of dengue virus.
The Mahidol vaccine was first successfully tested with laboratory animals. Further tests with between some 200 children and adults found that just one-shot of the vaccine helps develop immunity in the small group of volunteers and that prevents virus infection.
In the next stage, or phrase three, Prof. Suthee said, his team will produce a larger amount of the vaccine to use on tests with a large group of between 3,000-5,000 volunteers in the central province of Ratchaburi. This is expected to be completed in 2007.
Dengue has infected 7,200 people in Thailand as of early May 2005, of whom 12 have died, up from seven deaths in the same period last year, according to Department of Disease Control chief Thawat Suntrajarn.
ziop from Rodman
FDA's refusal to grant SPA complicates Ziopharm's Phase III plans
Click for Full PDF
It is unusual for Rodman to issue a negative report, but then again Jefferies and JMP securities did the last raise so they may be upset.
The News: In a surprise announcement (to us and most investors) Ziopharm announced this morning that the FDA did not grant the company an SPA for the proposed Phase III trial of palifosfamide+doxorubicin in metastatic soft tissue sarcoma, (PICASSO III). According to the company, the FDA does not view the current endpoint of PFS “as supportive of an SPA”, and suggested that Overall Survival (O/S) is the more appropriate primary endpoint for the Phase III trial. The company “intends to request a meeting with the FDA” to further discuss the situation, while it is weighing its options, i.e whether A) to go forward with its original plan of keeping PFS as the primary endpoint in its path for accelerated approval, despite the agency’s refusal to view this as an appropriate enpoint to grant an SPA for PICASSO III, and to use Overall Surival as the primary endpoint for full approval, should accelerated approval be granted, or B) go along with the agency’s views and change the trial’s endpoints, and possibly accept Overall Survival as the new primary endpoint, despite the lack of sufficient data from the Phase II setting. In addition, the company has now guided that it is delaying the start of Phase III trial, pushing out its start from 1H 2010 to 3Q2010. Based on the new uncertainty around the company’s lead program introduced by today’s developments, we are placing our rating on ZIOP Under Review without a target price until we have more clarity around the design of the Phase III trial.
Our take on this news: This is definitely not a positive development for ZIOP: first of all, management has appeared very confident, even until very recently, about the company’s chances of securing an SPA, which makes us believe that either management had misread the situation/the agency’s signals, or that there was a last minute change in the direction of the discussions with the FDA about the suitability of PFS as the primary endpoint for the trial. Secondly, and more importantly, this news significantly complicates the situation for ZIOP, in that approval of palifosfamide may now be dependent on an endpoint (Overall Survival) we have seen very little data on. This is not to say that palisfamide now has less chances of succeeding in Phase III; however, the situation has now changed into one where investors may have to gauge how palifosfamide will perform in Phase III in terms of O/S, based on how the compound did in terms of PFS in a small (albeit randomized) Phase II trial.
What’s next for ZIOP? 1) The new meeting with the FDA that the company “intends to request” on the registration path for palifosfamide, 2) and the initiation of the pivotal Phase III trial in STS with palifosfamide are the next most important catalysts for ZIOP, which is now pushed out to 3Q 2010. In addition, we could still see 3) a worldwide or regional partnership for palifosfamide at any point this year (if not an outright acquisition), which could obviously be a very significant event for the stock, depending on the economics and other terms of the deal and on who the partner is. However, we see today’s news as taking at least some of the wind behind palifosfamide sails, given that any potential partner may now be spooked with the FDA’s position and may choose to instead wait until positive results before investing in palifosfamide. Other expected, (much) less impactful, events include the following:
4) initiation of a Phase I trial with the oral formulation of palifosfamide
5) completion of the Phase I trial with the oral formulation of darinaparsin
6) completion of the EOP2 meeting for darinaparsin
7) initiation of a pivotal trial of darinaparsin for the treatment of PTCL
Valuation: We are currently placing our rating on ZIOP Under Review without a target price. We had orginally assigned ZIOP shares a Market Outperform rating and a 12-month target price of $8/share, and had arrived at our target price by applying a 25x P/E multiple to our fully diluted projected 2014 EPS of $1.16 and discounting back using a 40% discount rate. However, given the uncertainty introduced around the company’s lead program, we are placing our rating Under Review until we have more clarity on the future of the Phase III program.
nnvc...It isn't very often that the board gets the opportunity to buy a stock with a market cap approaching 300 million that does studies in test tubes, and sometimes they even get into mice, like todays release.
can you explain why this company is undervalued in your eyes?
Is it posible that ziop might have had an inkling that the spa discussions were not going as expected when they raised money on May 27th?
I am sure nnvc will continue for have great pre clinical data for the next 20 years.
What is your timeline for them to start human trials, 30 years?
you pounce on every post that I make.
to claim my posts make no sense or untrue is very strong language. I think I deserve more than that.
CYPB announced it in-licensed the North American development and commercial rights for CYP-1020 from BioLine Rx (TASE: BLRX, not rated, NIS 445).
In our view, assuming Phase III results (most likely 2-3 years away) demonstrate improvement in cognition (in addition to expected positive anti-psychotic effects), CYP-1020 could potentially be profiled as a major drug; an event that could be transformative for CYPB. CYP-1020’s composition of matter protection could last until 2031.
However, these events (Phase III results and approval) are years away and CYPB has a fundamental problem to solve in the meantime: leveraging its existing commercial infrastructure.
CYP-1020 is an anti-psychotic candidate that links (by an ester bound) a dopamine antagonist (perphenazine: an old typical anti-psychotic) and GABA. The most notorious potential result of adding a GABAergic effect (to the anti-psychotic effect of perphenazine) is the improvement of cognition. Cognition deterioration remains a major medical need in schizophrenia not addressed by current therapies.
In fact, CYP-1020’s pro-cognitive effects were evidenced in a Phase IIb six week, double blind, placebo and active-comparator (risperidone) controlled multinational study (the EAGLE study). In EAGLE, cognition was evaluated using the Brief Assessment of Cognition in Schizophrenia (BACS) composite score. The results (at 6 weeks) indicated the CYP-1020 (at 20/30mg a day) group obtained a BACS improvement of 9.27 versus an improvement of 6.01 for placebo and 6.23 for risperidone (p=0.027 for both). Importantly, BACS scores continued to improve in a six week extension trial that was recently completed.
The primary efficacy endpoint was the change from baseline in the total score of the Positive and Negative Symptoms of Schizophrenia (PANSS). Results showed patients on CYP-1020 (at a dose of 20/30mg a day) experienced a greater PANSS reduction from baseline versus placebo (a LS mean of -23.6 vs. -14.4, p=0.002). LS mean PANSS score improvements with risperidone were -26.2 with no statistical significant difference between CYP-1020 and risperidone. Importantly, PANSS scores improvements were maintained for additional a six weeks in a recently completed extension trial.
Secondary efficacy endpoints, including the clinical global impression of severity (CGI-S) and change (CGI-C), favored CYP-1020. Importantly, there were no clinically relevant (or statistically significant) changes in weight, lipids and glucose or other common metabolic changes seen with the use of anti-psychotics.
Potential cash consequences: Cypress ended Q1 2010 with $137 million in cash and we previously estimated (pre BioLineRx transaction) the Company would end FY 2010 with $125.0 million. Incorporating the $30 million upfront payment and adding approximately $7 million in CYP-1020 related expenses, we now estimate CYPB will end 2010 with approximately $88 million.
Savella is CYPB’s primary source of cash. After incorporating expected 2011 and 2012 CYP-1020 expenses, we estimate CYPB could require north of $40 million in revenues to break even. To reach this level of revenues, Savella’s total revenues need to be >$250 million, a run rate we don’t forecast until early 2013.
Potential clinical and regulatory milestones to BioLineRx reach up to $160 million. However, the majority are related to demonstration (and claims) on improvement of cognition.
CYPB will hold a conference call today, Monday, June 21at 10:00AM EST at (866) 814-1916. We look forward to gaining a better understanding of the potential of CYP-1020 in upcoming days and potential CYPB strategic considerations on ways to leverage existing commercial infrastructure.
The hard and timely part in this game is designing the expression cassette that contains the vector and cDNA of interest. This part is pretty much the same for all players GENZ,PLX or iBio. Inserting this construct into agrobacteria and then infecting plants instead of inserting directly to cell culture might be a bit more rapid but then extracting from a whole plant instead of cells is longer. So, every system has its own pros and cons but saying iBio's is more versatile simply isn't correct
Putting genes into expression cassettes (if the cassettes already exist and work, like the iBioLaunch vectors do) is fast and easy, especially now that whole genes can be synthesized from scratch rapidly and cheaply by any number of high-quality service providers.
Extracting and purifying proteins from plant tissue instead of cultured cells is not more difficult or longer. I don’t know where that concept comes from, but it is incorrect, and has been proven incorrect not only by iBio and Fraunhofer, but also by other groups working with plants.
iBio’s system is much more versatile than cell culture systems or any approach that requires creation, selection and stabilization of transgenic organisms of any type.
I can't go into it anymore on the board but I wanted to respond.
Affymax® to Hold Conference Call and Webcast on Monday, June 21, 2010 at 8:00 a.m. Eastern Time
Another one of those, did the trial work or not.
I think not
Companies:Affymax, Inc.
Press Release Source: Affymax, Inc. On Sunday June 20, 2010, 5:00 pm EDT
PALO ALTO, Calif.--(BUSINESS WIRE)--Affymax, Inc. (Nasdaq: AFFY - News) today announced that its management team will host a conference call and webcast tomorrow, Monday, June 21, 2010 at 8:00 a.m. Eastern Time (5:00 a.m. Pacific Time).
Conference Call Details
To access the live conference call tomorrow, Monday, June 21, 2010 at 8:00 a.m. Eastern Time via phone, please dial 877-354-4057 from the United States and Canada or +1-224- 357-2391 internationally. The Conference ID is 83101977. Please dial in approximately ten minutes prior to the start of the call. Individuals interested in listening to the live call via webcast may do so by visiting http://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fwww.affymax.com&esheet=6334031&lan=en-US&anchor=www.affymax.com&index=1&md5=0641ee06dd8930f413ec3e90c616e902 and clicking on the "Investor Relations" section. A replay of the webcast will be available on the Company's website for 30 days.
About Affymax, Inc.
Affymax, Inc. is a biopharmaceutical company committed to developing novel drugs to improve the treatment of serious and often life-threatening conditions. For additional information, please visit http://us.lrd.yahoo.com/_ylt=AuEcUGaxPz.8_aDoiVPmMfPjba9_;_ylu=X3oDMTE2OHI0ZzU1BHBvcwMyBHNlYwNuZXdzYXJ0Ym9keQRzbGsDd3d3YWZmeW1heGNv/SIG=165k53uf8/**http%3A//cts.businesswire.com/ct/CT%3Fid=smartlink%26url=http%253A%252F%252Fwww.affymax.com%26esheet=6334031%26lan=en-US%26anchor=www.affymax.com%26index=2%26md5=f64b9083af2aa8bc31062934a4759bd3.
On this particular issue I agree with walstarb
Genzyme has cash flow but they should spend their money on straightening out their manufacturing issues.
the only reason to put this buy back into place was because Icahn probably told them that he intends on blowing out of the stock so the buyback will be to soften the blow of his selling.
the rhucin phase 3 data
The 28-patient Phase III trial for the orphan indication of hereditary angioedema was stopped early on August 20 on the advice of EU regulators because the magnitude of benefit of Rhucin made it unethical to keep some patients on placebo.
The interim results showed that Rhucin-treated patients reported their first relief of symptoms (the primary endpoint) at a median time of 60 minutes compared with 8.5 hours for those who received placebo, with a highly significant p-value of 0.0009.
In addition, patients on Rhucin had minimal symptoms at a median time of 6.1 hours compared with 20.2 hours for patients on placebo (p=0.0038)
The analysis demonstrated that 100% of the Rhucin patients responded to treatment and had sustained relief without a relapse of their attack symptoms, said Pharming.
the cynryse phase 3 data
, with a median time to sustained symptom relief of 2.0 hours for patients receiving C1-INH compared to greater than four hours, the maximum evaluation period, for patients receiving placebo (p=0.026)
I would prefer the recombitant form of the drug as opposed to pooled plasma even if equivalent. but I think it has an advantage.
The market cap is cheap considering where they are in Europe.
I do not know why every argument has to have a winner. I do not own the stock but the more I am writing about it and looking into it the more I think I will buy some next week.
try not to be so stressed.
this was an error in my last post. This refers to jerini's product
Firazyr causes a bee-sting like reaction. docs know it missed the primary endpoint in the randomized trial and Shire is having difficulty even recruiting patients.
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regarding csl and viropharma
Parents and docs are reluctant to use a pooled plasma version when a pure human recombinant version of the same is available with better efficacy.
Look what happened to the Factor VII and insulin markets when the pure human proteins were made available. The market switched completely over to the pure human recombinant version.
The response rate for Cinryze in acute is over 93%. Berinert (CSL) data in acute is quite good as well. Rhucin isn't going to work 100% of the time, so you must be splitting hairs or making it up as you go along.
Does CSL work in laryngeal and abdominal HAE? Pharmings does.
CSL product is pooled plasma isn't it -- they don't like the viral contam risk
In the U.S. Rhucin will have to break CSL's Orphan status to get on the market at all. And even then, I'd expect Rhucin US sales to be de minimis.
Of course, I am not privy to any information under a CDA so I haven't seen the FDA minutes, but I have always been told by all management that the FDA views human recombinant a separate drug to pooled plasma, they both have separate BLA filings,
There would be 3 companies splitting the smaller acute market (CSL, Dyax, Pharming) and Rhucin isn't sufficiently differentiated.
I think dyax is dead if Rhucin gets approved here. The data is better and dyax had cases of Anaphylactic Shock.
In Europe not only are C1's available but also Firazyr which is a pretty good drug for acute yet only sold $6M worth in 2009. I'd expect Rhucin sales to be less than Firazyr.
At investigator meetings no one wanted to use pooled plasma, in EU there is a larger concern of viral contamination compared to here. they have had more problems with viral contimination.
Firazyr causes a bee-sting like reaction. docs know it missed the primary endpoint in the randomized trial and Shire is having difficulty even recruiting patients.
Nothing of course. That's the downside to profit split deals for small biotech, they start out as loss sharing agreements. The question is at what level of sales will it start throwing off cash to ADLR.
Profit split deals are usually where you also split the costs in the same proportion as the profit split.
In this case I think gsk has about 4 or 5 times the number of salepeople that Adlr has with a 50/50 split.
what this does show is how difficult it is to sell a new product into the hospital space.
Adolor's problems is one of the reason I stayed away from Javelin.
it is more versatile because it can be used for vaccines where you need to react quickly. A trangenic product could not do that.
If they get a bad batch they can throw it out and infiltrate more plants. That wouldn't be as simple for Protalix.
It sounds complicated but the process is actually very simple
The response rate was better than cinryse for acute, but cinryse is better for prevention because of the half life
They use rhucin when someone has a breakthough attack that is on cinryse.
Pharming provides update on outstanding shares
Pharming has needed to do some awful financings but their drug is better then the other ones approved for HAE. they will probably recieve European approval by the end of the month.
Companies:PHARMING GROUP NVPHARMING GRP NV LEID
Press Release Source: Pharming Group N.V. On Friday June 18, 2010, 12:10 pm EDT
LEIDEN, NETHERLANDS--(Marketwire - 06/18/10) -
Leiden, The Netherlands, June 18, 2010. Biotech company Pharming Group NV ("Pharming") (NYSE Euronext: PHARM) today announced that its current number of outstanding shares has increased from 277,206,421 at June 2, 2010 to 285,691,836 as per today. The increase reflects an aggregate number of 8,485,415 shares issued in relation to various conversions of bonds issued in January 2010. As a result of these conversions, the original nominal value of the bonds issued in January 2010 in the amount of EUR7.5 million has decreased to EUR2.0 million today.
About Pharming Group NV Pharming Group NV is developing innovative products for the treatment of genetic disorders, ageing diseases, specialty products for surgical indications, and nutritional products. Pharming's lead product Rhucin® for acute attacks of Hereditary Angioedema has passed clinical development stage and the Market Authorization Application is under review with the European Medicines Agency. Prodarsan® - a product under development by Pharming's subsidiary DNage - is in early stage clinical development for Cockayne Syndrome and lactoferrin for use in food products. The advanced technologies of the Company include innovative platforms for the production of protein therapeutics, technology and processes for the purification and formulation of these products, as well as technology in the field of DNA repair (via DNage). Recently the partial spin- out of DNage was initiated. Additional information is available on the Pharming website,http://www.pharming.com.
Link to the presentation of a company that has a more versatile technology than Protalix does in the ability to produce protein therapeutics, antibodies and plants from off the shelf green plants grown hydroponically.
http://noble.mediasite.com/mediasite/SilverlightPlayer/Default.aspx?peid=df9f61597c6b436eafc8099ef73216501d
They have invested so much in the sales force until now, if they really think that they will break even on their profit split to cover the sales force now the salesforce becomes an asset to inlicense a product to put into their bag.
This is why the javelin purchase by Myriad made no sense. They would have had to spend a hundred million on a sales force before they would have had a chance to make money
Adlr actually has leverage in their sales foroce. They have thirty salespeople and I think their partner has 150 to 200, but they have a 50/50 split.
If they needed the same size salesforce as gsk they would have been bankrupt.
they are spending a lot more on the sales force for the revenue split they are collecting.
billions for flumist
that's what I thought
Aside from the fact that Icahn wanted Medimune sold, has AZN gotten anything from the billions that they paid for the company?
Equity Research Wachovia Neurocrine Biosciences, Inc.
NBIX: Positive Daisy Petal Results. Partnering H2 2010?
• Summary: Yesterday (5/25), Neurocrine hosted a conference call to discuss
positive top-line results for the Phase II elagolix Daisy PETAL study in 132
endometriosis patients. Statistically significant reductions versus placebo were
observed in the co-primary endpoints of dysmenorrhea and non-menstrual
pelvic pain and the exploratory endpoint of dyspareunia (all p<0.001).
Importantly the study utilized a novel, more sensitive daily diary scale to assess
efficacy, which was requested by the FDA. These data will help finalize a Phase I
and II data package in over 700 patients and will be the basis for discussions
with the FDA during a Q3 End of Phase II meeting. Management has noted that
it has no intentions of conducting Phase III studies without a licensing partner
due to the large costs necessary to advance the compound and we believe these
data help increase the likelihood of signing a licensing agreement. However due
to a lack of clarity on the Phase III requirements (i.e., endpoints, length of study,
etc.), uncertainty around timing of a partnership, and belief that Neurocrine is
fairly valued at $3.50-4.50/share we are maintaining our Market Perform rating.
• Consistent Profile. The Daisy-Petal study randomized 132 women in a 1:1
fashion to either placebo or 150 mg/daily for 8 weeks after an initial one month
period (no drug or placebo) where women recorded their daily baseline in an
electronic diary. These top-level results reflect unblinded treatment group initial
2 month efficacy results but the patient-level results are still blinded. After the
initial 8-week period all patients are switched to elagolix until study completion.
The co-primary endpoints of dysmenorrhea and non-menstrual pelvic pain
scores decreased by 1.13 and 0.47 points from baseline in the elagolix arms (p<
0.001 and 0.01, respectively) and the exploratory endpoint of dyspareunia (FDA
requested) decreased 0.61 points (p<0.01). The elagolix results are consistent
with data from European Tulip-Petal (703) study vs. placebo and active control
leuprorelin which was in a less severely affected patient population. Importantly
a responder analysis requested by the FDA for the Daisy-Petal co-primary
endpoints achieved significant results with a near doubling of response rates for
dysmenorrhea and non-menstrual pelvic pain (63% vs. 33%). The secondary
endpoints for daily and monthly scales (the PGIC, EHP-5, and CPSSS) were all
significant and robust. Finally, the drug continues to be well-tolerated with no
Serious Adverse Events (similar to Tulip-Petal) and nausea being most common.
Valuation Range: $3.50 to $4.50
We value Neurocrine based on a sum of the parts analysis. On a risk adjusted NPV
basis using a required IRR of 20-35%, we believe elagolix is worth about $40-75
million or $1.00-2.00 per share using 40 million shares outstanding. Neurocrine
will end 2010 with approximately $45 million in cash, cash equivalents and
marketable securities. We arrive at a current valuation range of $150-200 million
or approximately $3.50-4.50 Neurocrine's primary risks are an inability to sign
licensing partners for any of its compounds. Clinical failure of elagolix would also
have a negative impact on shares.
Investment Thesis:
Neurocrine Biosciences is a neuroscience company whose lead candidate, elagolix,
is in Phase II development for endometriosis. Early data is encouraging however,
the drug has yet to demonstrate significant improvements in non-menstrual pelvic
pain, a key endpoint for regulators.
There are rules and mdco screwed up
sue the lawyers if they have a problem
stop trying to get congress to pass a law that helps them retroactively. It isn't supposed to work that way.
maybe you should stop smoking those stinking cigars and cleaning sewers for a living.
can you blame her. No drug could overcome those obstacles
Attached is David Yee's analysis of several melanoma drugs, including a preview melanoma at the ASCO meeting next week.
Targeting Melanoma
Novel Therapies in Phase III
Unlike the case for several other cancers, no
targeted therapies have been approved by the
FDA for the treatment of malignant melanoma.
• Here, we highlight three agents currently in phase
III trials. Each has the potential to be the first
targeted melanoma therapy, although each has a
slightly less than 50/50 shot at approval.
• The American Society of Clinical Oncology (ASCO)
meeting next week will feature a plenary
presentation relating to Bristol-Myers Squibb?s
(BMY) ipilimumab, an anti-CTLA-4 antibody. Prior
to that presentation, we model an inThought
Approvability Index (IAI) of 44%(D) for ipilimumab
in melanoma.
• Roche (RHHBY) and Plexxikon?s (privately held)
PLX4032, a kinase inhibitor specific for the
V600E mutant of BRAF, has been generating
significant excitement with anecdotal evidence of
efficacy. Its IAI score is 45%(D).
• Genta?s (GNTA) Genasense (oblimersen), an
antisense agent targeting Bcl-2, has been struggling
to demonstrate efficacy for a decade. We model a
45%(D) IAI for melanoma.
• The IAI uses historical approval rates and detailed
analysis of clinical trials to model the probability of
approval. The letter grade indicates relative
progress in the current phase ? in the case of these
three drug candidates, a lower than average
probability of timely advancement to regulatory
review.
Malignant melanoma is the seventh most common
cancer in the U.S., with about 69,000 new cases
and about 9000 deaths per year. It has few
therapeutic options, with only three agents
approved by FDA for its treatment: hydroxyurea,
which is no longer used; dacarbazine, which was
approved in 1975; and Proleukin (aldesleukin),
which was approved in 1992. Other
chemotherapeutics (e.g. Temodar) are used offlabel.
Intron A is approved for adjuvant therapy of
melanoma in patients who are at high risk for
relapse.
Progress in melanoma drug development is woefully
lagging breast cancer, chronic myeloid leukemia,
and colorectal cancer, where targeted agents have
improved care significantly. Disappointments have
been abundant in this indication, the latest being
Nexavar (sorafenib), a targeted therapy approved
for use in kidney and liver cancer. Nexavar was in
phase III development for melanoma in combination
with carboplatin and paclitaxel, but its PRISM study
was suspended in April 2009 when the primary
endpoint of progression-free survival (PFS)
was not met.
This report examines three targeted agents
in phase III development for melanoma
hoping to buck the trend and become the
first new melanoma drug in nearly twenty
years.
Genasense
Genta?s Genasense (oblimersen) is an
antisense oligonucleotide that targets bcl-2
expression. bcl-2 helps prevent cells from
committing cell suicide (apoptosis), and Genasense
would presumably sensitize the melanoma cells to
apoptosis by its inhibition.
Genasense for melanoma was first filed with the
FDA in December 2003, but Genta withdrew the
NDA when ODAC recommended against its approval
in May 2004. Not to be discouraged, Genta noted
that patients with normal serum levels of LDH
(lactate dehydrogenase) exhibited significantly
better responses in terms of progression-free
survival and overall survival than patients with
elevated serum levels of LDH. The company then
sponsored another phase III trial which selected for
patients with normal LDH levels (about two-thirds
of melanoma patients) to receive dacarbazine with
or without oblimersen. This AGENDA trial was
initiated in July 2007 and is expected to be
completed in March 2011
Antisense technology has not had a good track
record, and it is doubtful that Genasense will be
able to buck this trend. Preliminary results to be
presented in two posters at ASCO next week suggest
a ?modest improvement in PFS? of one month with
the addition of Genasense to dacarbazine.
If the AGENDA trial is not successful, Genta has a
backup plan in phase I development, which involves
the addition of Genasense to a combination of
Abraxane and Temodar. Results from this latter
project will also be presented at ASCO.
We assign an IAI score of 45%(D) to Genasense for
melanoma.
Ipilimumab
Bristol?s ipilimumab is a monoclonal antibody that
targets CTLA-4. According to Dr. Jason Chesney,
Associate Director of Translational Research at the
James Graham Brown Cancer Center of the
University of Louisville KY, CTLA-4 ?is a brake on
the immune system, and removing the brake should
elicit a more heightened response against
the melanoma cells.? Unfortunately,
removing the brake on the immune system
can also cause serious autoimmune
reactions. Although the latter can be
ameliorated with steroids, Dr. Chesney
notes that there appears to be a
correlation between autoimmune response
and clinical response, so that treatment
with steroids may also render ipilimumab
less effective against the melanoma. The
use of this agent against melanoma will be
represented at ASCO by five abstracts,
including a plenary presentation. We assign it an IAI
score of 44%(D).
Pfizer?s tremelimumab, a similar monoclonal
antibody directed against the same target (CTLA-4),
was previously in phase III development as well, but
an interim analysis indicated that its use in
combination with dacarbazine or temozolomide
would not prove superior to current treatment;
therefore, it has been returned to phase II.