The American Diabetes Association (ADA) this week called for a new evaluation of clinical data on drugs used to control blood sugar for patients with type 2 diabetes. They include Merck & Co’s $4 billion a year Januvia franchise, Novo Nordisk’s Victoza, and Byetta and Onglyza from Bristol-Myers Squibb Co and AstraZeneca Plc, among others.

“People who are taking these medications, or who may consider taking them, should have the benefit of all that is currently known about their risks and advantages in order to make the best possible decisions about their treatment,” Dr. Robert Ratner, ADA’s chief scientific and medical officer, said in a statement.

The medicines are called incretin mimetics because they mimic hormones the body produces to stimulate release of insulin, and are from classes of drugs known as GLP-1 receptor agonists and DPP-4 inhibitors. GLP-1 drugs boost insulin production by the pancreas and slow absorption of food. DPP-4 inhibitors block an enzyme the breaks down the GLP-1 peptide in the gut, thereby increasing insulin production.

The U.S. Food and Drug Administration in March said it was studying unconfirmed reports that the drugs cause inflammation of the pancreas and pre-cancerous changes to cells in the pancreas. European health regulators are also studying the issue.

Around the same time, new concerns arose from a small study conducted by a leading diabetes expert, Dr. Peter Butler, from the University of California, Los Angeles.

Butler examined human pancreases from patients who had died of causes unrelated to pancreatic disease and found more pancreas lesions and one cancerous tumor in those who had taken Januvia or Byetta compared with nondiabetics or diabetics who had not taken those medicines.

More than 370 million people are living with diabetes worldwide, with type 2 accounting for 90 percent to 95 percent of the cases, according to the International Diabetes Federation. Without significant lifestyle changes to curb obesity and other causes of diabetes, that number could balloon to as many as 552 million by 2030, the organization projected.

NO FIRM EVIDENCE OF RISK

Bristol-Myers and AstraZeneca issued a joint statement expressing support for the ADA initiative. Merck said it is committed to participating in the ADA effort, and is separately conducting a 14,000-patient heart safety study of Januvia.

Danish drugmaker Novo Nordisk, in an emailed comment, said its studies to assess safety signals of its $1.8 billion a year Victoza do not reveal any evidence of increased risk of pancreatitis or pancreatic cancer.

“As far as the ADA proposal is concerned, this is something that I do support from a conceptual basis,” said Alan Moses, Novo’s global chief medical officer, in a telephone interview.

“In principle, Novo Nordisk absolutely supports working with the other companies, but the final details depend on what specifically is being proposed,” Moses said, adding “it all depends on the credibility of the data that’s being evaluated.”

The safety concerns are being discussed on Wednesday and Thursday at a workshop conducted by the National Institutes of Health (NIH) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).

A document outlining the FDA’s presentation at the workshop was handed out at the meeting. Attendees quoted it as saying the agency review of trial data on the drugs did not provide enough evidence to say whether there is a link to pancreatitis, and that long-term study would be required to determine any cancer risk. A FDA spokeswoman could not immediately confirm the contents of the document.

“The FDA basically appears to just be saying ‘look, there just isn’t enough information here to make an informed decision’,” said Mark Schoenebaum, a drug industry analyst with ISI Group who was attending to two-day NIH/NIDDK workshop.

“There are no conclusions at this point in time from the meeting and I doubt very much there will be because the science quite frankly is immature about the whole area of pancreatic cancer,” said Novo’s Moses, who will address the workshop on Thursday. “Everybody agrees that this is an incredibly complex area.”

In an interview with Reuters earlier this week Peter Stein, Merck vice president of clinical research for diabetes, expressed full confidence in the safety of Januvia.

During the workshop, Merck said it will present data on the safety profile of Januvia, known chemically as sitagliptin, including an updated analysis of data from more than 14,000 patients from 25 randomized clinical trials.

Merck last month reported a surprising decline in first quarter sales of Januvia, which has been the drugmaker’s fastest growing medicine since its 2006 approval. It was not clear if increased competition, safety concerns or other factors led to the 4 percent slip in quarterly sales to $884 million.

(Reporting by Bill Berkrot and Ransdell Pierson)

The U.S. biotechnology company had previously released
positive data from the 500-patient Phase III trial called
Palace-1 that compared its drug, apremilast, to a placebo
through 16 weeks of treatment.

The data being presented at the European League Against
Rheumatism in Madrid followed those patients through 52 weeks of
treatment to assess longer term effectiveness and safety of
apremilast.

At 52 weeks, 63 percent of patients who received 20
milligrams of apremilast twice daily and 55 percent who took 30
mg of the Celgene drug twice a day achieved at least a 20
percent reduction in signs and symptoms of the disease, such as
painful, swollen or tender joints – a measure known as ACR 20.

That represented an improvement over time of the ACR 20
rates seen at 16 weeks. At that point of the study, 31.5 percent
of the 20 mg patients and 50.8 percent of the 30 mg patients had
achieved ACR 20.

Improvements were also seen in the number of patients who
achieved 50 percent and 70 percent reductions in signs and
symptoms of the disease as well, Celgene said.

At 52 weeks, 24.8 percent of those who got the 20 mg dose
reached ACR 50 and 15.4 percent achieved ACR 70. For the higher
dose of apremilast, 24.6 percent achieved ACR 50 and 13.8
percent hit ACR 70.

Psoriatic arthritis is a chronic inflammatory condition in
which joint pain is caused by the immune system attacking
healthy tissues. It affects about 30 percent of those who suffer
from the painful and unsightly skin condition psoriasis.

Celgene earlier this year applied for U.S. approval for
apremilast to treat psoriatic arthritis based on the results of
this and two other late stage trials. It is planning to seek
U.S. approval for apremilast to treat psoriasis later this year.

Patients in the Palace-1 study had previously been treated
with oral disease modifying drugs, such as methotrexate, and/or
biotech treatments known as anti-TNF drugs, such at AbbVie’s
Humira. It also included patients who failed to be
helped by prior treatment with anti-TNF drugs.

Apremilast is a pill that inhibits an enzyme known as
phosphodiesterase 4, or PDE4, and acts to reduce inflammation.

No serious safety issues, such as major heart problems,
cancers, opportunistic infections or tuberculosis were reported
for the 52 weeks of the trial.

Based on the results, apremilast appears to be somewhat less
effective but safer than the widely used injected biologic
anti-TNF medicines.

“There is a high unmet medical need for additional
efficacious, well-tolerated treatment options for patients with
psoriatic arthritis,” Dr. Arthur Kavanaugh, who will present the
data in Madrid, said through an email.

The Phase III trial tested Stelara at two doses against a
placebo in 312 patients with active psoriatic arthritis, and
included both subjects who had previously been treated with
widely used biotech drugs from a class known as anti-TNF
medicines and those who had not.

At week 52, 46.8 percent of those who received the 45
milligram dose of Stelara and 48.4 percent of those to got 90 mg
had at lease a 20 percent reduction in arthritis symptoms, such
as swollen and tender joints – a measure known as ACR 20.

The company had previously reported results through 24 weeks
of treatment in which nearly 44 percent of those who received
Stelara at either dose achieved ACR 20 versus 20.2 percent who
reached ACR 20 in the placebo group. The result was deemed to be
highly statistically significant.

Nearly 56 percent of the placebo patients who crossed over
and began taking 45 mg Stelara at week 24 had achieved ACR 20 by
week 52, researchers said.

The data was being presented at the European League Against
Rheumatism meeting in Madrid this week.

Psoriatic arthritis is a chronic inflammatory condition in
which joint pain is caused by the immune system attacking
healthy tissues. It affects about 30 percent of those who suffer
from the painful and unsightly skin condition psoriasis. Many
patients are treated with anti-TNF drugs such as AbbVie’s
Humira and J&J’s own Remicade.

Researchers also measured ACR 50 and ACR 70 scores,
representing 50 and 70 percent improvement in symptoms.

For those who received 45 mg of Stelara, 27.7 percent
reached ACR 50 and 12.8 percent hit 70 percent improvement after
52 weeks. At 90 mg, 26.3 percent achieved ACR 50 and nearly 18
percent hit ACR 70.

For those patients who started on placebo and took Stelara
from week 24 through week 52, 28.6 percent achieved ACR 50 and
15.6 percent reached ACR 70, researchers said.

Stelara, known chemically as ustekinumab, is already
approved to treat psoriasis. The medicine is currently under
review for a psoriatic arthritis approval in the United States
and Europe.

“One of the major unmet needs in psoriatic arthritis is for
patients who have an inadequate response to anti-TNF agents or
who for whatever reason cannot take anti-TNFs who really don’t
have good alternatives,” Dr. Christopher Ritchlin, the study’s
lead investigator, said in a telephone interview.

“Those of us who treat large numbers of these patients have
been struggling with options,” said Ritchlin, who will present
the study results on Wednesday.

“Now we have another agent besides anti-TNF agents that can
provide relief for the skin and joints. These data add a new
option that we didn’t have before,” he said.

Stelara proved more effective in patients who did not
receive prior treatment with anti-TNF drugs, researchers said.
However, they noted that previously treated patients had more
active disease at the start of the trial.

The drug was well tolerated with no deaths or cases of
tuberculosis reported, researchers said. Serious adverse events
were reported in 5.8 percent of Stelara patients, they said.

(Reuters) – Forest Laboratories Inc is trying to avert yet another bitter proxy battle with billionaire investor Carl Icahn ahead of its annual investor meeting this summer, according to two sources familiar with the situation.

Icahn, Forest’s second-largest shareholder, and the company have been in discussions over the course of the year and talks are ongoing to avoid a third proxy fight in as many years, the sources said.

There is, however, no guarantee of an amicable settlement, they said, and a mid-June deadline for filing a slate of alternative director candidates is fast approaching.

Neither Forest, which is searching for a successor to long-time Chief Executive Howard Solomon, nor Icahn could immediately be reached for comment.

Details of the discussions could not be learned. Icahn’s persistence underscores why in many boardrooms he is still regarded as one of the most feared activist investors.

He has been highly critical of Forest leadership in recent years, arguing that the company in which he holds an 11.5 percent stake has been badly managed and underperforms industry peers.

Icahn has criticized the U.S. drugmaker for being ill-prepared to generate future growth in the face of looming generic competition for two of its biggest selling products – the antidepressant Lexapro and the Alzheimer’s treatment Namenda – and for numerous warnings the company received from U.S. health regulators related to marketing practices of its drugs.

His campaign against the company has met with limited success. Last year’s proxy battle, for example, ended with just one of Icahn’s four nominees being elected to the board – Pierre Legault, the former chief financial officer of OSI Pharma.

Legault has since distanced himself from Icahn, telling people that he didn’t know the investor well and wasn’t “his guy”, one of the sources said.

Legault declined to comment.

Forest has also been taking steps that would blunt some of that criticism. The company has launched new products over the past two years. The company’s share price is up about 18 percent since last August, beating the 14 percent gain for the broader S&P 500 over that time period.

Icahn had also accused the Forest CEO of planning to install his son as his successor without a proper review of potential candidates for the top post.

That challenge may have been eclipsed by recent events. In May, Forest said Solomon would retire at the end of the year after more than 35 years of running the U.S. drugmaker. It said an independent committee from the board was evaluating internal and external candidates for the top job. Solomon was to remain chairman and would be a candidate to retain his seat on the board.

One potential CEO candidate could be Bausch & Lomb Chief Executive Brent Saunders, who is on Forest’s board. The sources said it was still too early in the CEO search process to know if he would be a candidate.

Saunders declined to comment.

Saunders, a highly regarded executive with turnaround expertise, is expected to leave the eye care maker following a transition period once its recently announced acquisition by Valeant Pharmaceuticals International is completed.

That could take place as early as this summer, a person familiar with the proceedings said, leaving the former Schering-Plough executive a sizeable window to help with the transition before Solomon steps down.

(Reporting by Bill Berkrot and Nadia Damouni; Editing by Paritosh Bansal and Andrew Hay)

Those who received Avastin in the late-stage study of 637
previously untreated patients also experienced more side
effects, such as low platelet counts, blood clots and elevated
blood pressure. Researchers said the toxicity was not severe
enough to preclude use of Avastin, or bevacizumab, had it helped
patients live longer.

The data presented at the American Society of Clinical
Oncology (ASCO) meeting in Chicago could jeopardize Avastin’s
accelerated, or conditional, U.S. approval.

Glioblastoma is the most common as well as most aggressive
form of primary brain cancer, affecting about 100,000 Americans
each year. Avastin currently has conditional U.S. approval for
use against glioblastoma that has recurred after initial
treatment, but some oncologists have been using it off-label as
a first-line treatment.

“Unless we can identify a group of patients that clearly
benefits from early use of bevacizumab, it appears that it
should not be used in the first-line setting,” Dr. Mark Gilbert,
the study’s lead investigator from MD Anderson Cancer Center in
Houston, said in a statement. Avastin “remains an important part
of our armory against glioblastoma, but in most situations it
should be reserved as a salvage regimen.”

In the study led by Gilbert and sponsored by the Radiation
Therapy Oncology Group, newly diagnosed glioblastoma patients
following surgery received either the Merck & Co brain
cancer drug Temodar plus radiation or the chemo and radiation
therapy plus Avastin.

The median overall survival was 16.1 months for the control
group versus 15.7 months for the Avastin group.

Those who received Avastin on average went longer before
their tumor started to grow – known as progression-free
survival, or PFS – but the difference of 10.7 months versus 7.3
months was not deemed to be statistically significant,
researchers said.

Researchers also found that patients who received Avastin
suffered more symptoms and other measures of diminished quality
of life, compared with the control group.

In a separate study of 921 patients sponsored by Roche that
was required by the U.S. Food and Drug Administration as a
condition of the accelerated approval, Avastin also failed to
prolong survival. In that study, Avastin plus chemotherapy and
radiation led to median survival of 16.8 months, compared with
16.7 months for those who did not get Avastin.

In data from the study that was previously reported, the
Avastin group did go longer before the tumor began to grow again
- 10.6 months versus 6.2 months. However, it remains to be seen
whether the FDA will keep the glioblastoma approval in place
based on progression free survival but no actual survival
benefit.

The FDA previously withdrew a conditional approval for
Avastin in breast cancer after it failed to improve overall
survival.

Molecular profiles of tumor samples and imaging scans are
being examined to determine if there is any group of patients
that could still benefit from Avastin use in the first-line
setting, researchers said.

This marked the first study to demonstrate that a drug which
blocks blood vessel formation in the tumor can prolong the lives
of women with gynecologic cancers, researchers said.

In the study of 452 patients with cervical cancer that had
spread or returned, those who received Avastin on top of
chemotherapy on average lived for 17 months. That compared with
a median overall survival of 13.3 months for those who received
only chemotherapy. The result was considered to be statistically
significant.

“Improvement in overall survival is a huge deal in this
disease,” Dr. Krishnansu Sujata Tewari, the study’s lead
investigator, said in an interview.

The current standard treatment for cervical cancer that has
recurred or spread offers little hope, and patients tend to live
for 12 months or less.

“We finally have a drug that helps women live longer,” said
Tewari, who presented data from the study on Sunday at the
American Society of Clinical Oncology (ASCO) meeting in Chicago

Avastin, which had sales approaching $6 billion in 2012, is
approved in the United States to treat cancers of the colon,
lungs and kidneys, and – pending additional confirmatory data -
has conditional approval for a type of brain cancer. In some
overseas markets, it is also approved for ovarian and breast
cancer. A conditional U.S. breast cancer approval was pulled
after it failed to prolong survival in clinical trials.

An approval for treating advanced cervical cancer would open
another large market for the medicine in patients for whom
chemotherapy has been largely ineffective. About 4,000 women in
the United States and 250,000 worldwide die each year from the
disease.

The National Cancer Institute-sponsored study tested two
chemotherapy regimens against the Avastin combination -
cisplatin plus paclitaxel and topotecan plus paclitaxel – to
assess if topotecan performed any better than commonly used
cisplatin. Researchers found no significant differences in
survival between the two chemotherapy regimens.

Avastin with either chemo agent also met secondary goals of
the trial by improving progression-free survival (PFS), or the
time before the disease began to worsen, to 8.2 months versus
5.9 months for chemotherapy.

Tumor shrinkage rates were higher in patients who received
Avastin, known chemically as bevacizumab – 48 percent versus 36
percent for chemotherapy.

Researchers encountered no new or unexpected side effects
from Avastin use in cervical cancer, while those that were
observed did not significantly diminish patient quality of life.

“Not only did we not find any new side effects, but the
overall side effects that we did see were all under 10 percent,
which is considered to be an acceptable tradeoff when getting a
survival gain,” Tewari said.

The Food and Drug Administration (FDA) gave the green light to Tafinlar and Mekinist late on Wednesday, bringing the tally of new drugs approved by the U.S. agency so far this year to 13, compared with 11 at the same stage in 2012.

After 39 FDA approvals last year – a record only beaten in 1996 – the continuing healthy run-rate for so-called new molecular entities is fuelling investor hopes the industry may finally be pulling out of a long period of poor productivity.

The FDA approved the two GSK drugs to be used as single agents against melanoma – the deadliest form of skin cancer – and not in combination after the medicines delayed tumor growth in separate clinical trials.

GSK, however, hopes further trials now underway will prove there is an additional benefit from combining the treatments, potentially giving it an edge over Roche’s rival melanoma medicine Zelboraf.

After decades with virtually no progress in the fight against advanced melanoma and little to offer patients facing a virtual death sentence, Tafinlar and Mekinist mark the third and fourth new drugs approved by the FDA for metastatic melanoma in the past two years.

The drugs are a further step forward in targeted cancer care and will be used in patients with a specific genetic profile – an approach that will limit the number of people who get them.

As a result, sales expectations for the two medicines are relatively modest and analysts, on average, predict annual global revenue of $371 million for Tafinlar by 2017, with Mekinist expected to sell $425 million by the same time, according to forecasts compiled by Thomson Reuters Pharma.

FURTHER BOOST

Tafinlar, known chemically as dabrafenib, belongs to a class of cancer drugs called as BRAF inhibitors. Mekinist, or trametinib, inhibits a protein associated with cancerous tumors known as MEK.

Tafinlar was approved to treat patients with melanoma whose tumors express the BRAF V600E gene mutation, while Mekinist is for patients with either the BRAF V600E or V600K gene mutations. About half of skin melanomas have a BRAF mutation.

The FDA also approved the THxID BRAF test, made by France’s Biomerieux, which will be used to determine if a patient’s melanoma cells have the V600E or V600K mutation in the BRAF gene.

GSK also got further boost from another cancer drug late on Wednesday as its already marketed drug Arzerra, developed with Denmark’s Genmab, proved successful in a late-stage study as a first-line treatment for chronic lymphocytic leukemia (CLL).

Alongside the melanoma drug approvals, Deutsche Bank analyst Mark Clark said the Arzerra results represented “a triple dose of good news” for Britain’s biggest drugmaker.

So far, Arzerra has only be used in a subset of hard-to-treat CLL patients and analysts’ annual sales forecasts for the drug stand at $297 million by 2017, according to Thomson Reuters Pharma.

Deutsche Bank said this number was likely to rise as the medicine becomes a more viable competitor to Roche’s Rituxan, which is also known as MabThera.

Shares in Genmab, whose fortunes are closely tied to sales of Arzerra, jumped more than 7 percent in early trading on Thursday, while GSK was little changed in a broadly flat London stock market.

(Editing by John Wallace and David Holmes)

U.S. approval requirements for cardiac devices are much more
stringent than in Europe, where there is no centralized
decision-making body. But a growing number of U.S. heart doctors
feel the regulations are so demanding that patients are being
denied access to beneficial therapies.

From 2006 to 2011, European regulators approved
mid-to-high-risk medical devices, including heart devices, an
average of four years ahead of the more conservative U.S. Food
and Drug Administration, according to a report last year by
Boston Consulting Group. The quicker road to market in Europe
did not lead to a discernible increase in recalls or safety
problems, according to BCG and the California Healthcare
Institute, which conducted the study, and Eucomed, the European
trade group.

“There is frustration among the U.S.
investigators(researchers) and U.S. care providers around
delayed access to certain interventions that appear to be a
winner,” said Dr. Patrick O’Gara, a cardiologist with Brigham
and Women’s Hospital in Boston.

An example cited by several doctors is a replacement for
diseased heart valves made by U.S. device maker Edwards
Lifesciences. The Sapien transcatheter aortic valve
replacement (TAVR) system is particularly suited for elderly and
frail patients, since it can be put in place via a catheter
threaded through an artery rather than replacing a valve by
cracking open the chest for heart surgery.

“With this disease, if you wait two or three years, 60 or 80
percent of (patients) are dead. So not to have the most updated
version of the device to treat more patients like this doesn’t
seem to be a particularly good idea,” said Dr. Martin Leon,
director of the Center for Interventional Vascular Therapy at
Columbia University Medical Center in New York.

Heart disease remains the world’s No. 1 killer. An estimated
500,000 Americans suffer from severely diseased heart valves,
according to the American Heart Association. Many could be
candidates for valve replacements.

The approval delays are also costing device makers, such as
Edwards and Medtronic Inc, hundreds of millions of
dollars in potential sales while they are being asked to help
pay for U.S. healthcare reform through new taxes.

Dismay among heart doctors over delayed access to new
devices gained momentum at this year’s American College of
Cardiology (ACC) meeting, which featured several U.S. clinical
trials of devices long available in Europe.

One top researcher at the meeting called the United States
“a Third World country” when it comes to availability of
cutting-edge heart devices.

Only Edwards’ original Sapien valve has U.S. approval -
which it received in 2011, four years after Europe and
elsewhere. European cardiologists have been using a
next-generation version, which doctors find easier to maneuver
into place and believe may cause less trauma to the artery, for
three years.

That is why Leon, who is co-lead investigator of U.S.
clinical trials for both the original Sapien heart valve and the
smaller, newer Sapien XT, sends some patients to Europe for
treatment if he believes them better suited for the sleeker XT.

Medtronic has a similar heart valve replacement awaiting
U.S. approval that has been used in Europe since 2007.

Asked at the ACC meeting if he found the situation
frustrating, Dr. Gary Mintz, chief medical officer of the
Cardiovascular Research Foundation in New York, shot back: “You
mean because Algeria had TAVR before the U.S.?”

“Even the FDA recognizes the problem, but they are
answerable to Congress, not us,” Mintz said.

FDA’S BID TO STREAMLINE

The FDA requires proof of efficacy as well as safety through
carefully controlled, randomized clinical trials before
approving products, and may ask for long-term follow-up data.

“We recognize that some of our regulatory requirements have
been viewed as impediments compared to other parts of the
world,” said Andrew Farb, medical officer in the FDA’s division
of cardiovascular device evaluation.

The FDA is working on a new program to help streamline the
path to U.S. approval that would involve the agency much earlier
in device development – possibly discussing results with
researchers after use in the first patient, according to Farb.

The agency expects to publish this year its “early
feasibility study guidance,” which it hopes will outline a path
toward swifter reviews and approvals of devices in development
in the United States, Farb said.

“When you’re starting a new way of thinking, getting this
really ramped up is a challenge, but we’re hopeful,” he said.

Some companies, eager for faster returns on their
investments, have moved early-stage device trials overseas,
since they know they are likely to be able to begin selling the
products there years earlier. That has added to delays of U.S.
trials and approvals, Farb and others said.

Enrolling patients in randomized U.S. trials mandated by the
FDA is also being hampered by patient fear they would be put in
a control group that did not get the new device, doctors said.

Farb said the FDA is concerned by such trends and is seeking
ways to move early-stage human trials back to the United
States.

EUROPE MAY SEEK TIGHTER CONTROLS

In Europe, device makers must prove a product’s safety to
the satisfaction of one of some 80 designated regulator bodies
and show it functions as intended. Effectiveness is determined
through post-approval surveillance as it is used in patients.
Some European politicians view the system as too lax and have
called for a model closer to the U.S.

“I think we need to meet somewhere in between,” said Dr.
David Holmes, a cardiologist at the Mayo Clinic and a past ACC
president, of the two regulatory systems. He said Europe may
need to tighten its regulations without necessarily adding years
to its process.

One suggestion put forward by Eucomed – a device industry
trade group that represents thousands of companies – and others
would significantly cut the number of European regulators
allowed to approve higher-risk devices.

U.S. doctors are actively looking for ways to address the
issue. “We need a coalition of involved, thoughtful and balanced
individuals who see things on both sides of the equation and
look for every opportunity to shorten this time line,” O’Gara
said.

Holmes said such a coalition, including researchers,
manufacturers and physician groups like ACC and the Society of
Thoracic Surgeons, is looking to work more closely with the FDA
on the issue. He said the group is compiling a database of all
patients getting TAVR to enhance understanding of the
procedure’s long-term performance and aid the FDA in making
decisions.

MILLIONS IN LOST SALES

The approval lag means companies are leaving money on the
table when it comes to their newest devices.

Edwards’ original Sapien sells for about $32,000 per patient
and had U.S. sales of about $200 million in its first year on
the market. Had it been available in the United States at the
same time as Europe, the company could have rung up at least an
additional $800 million in sales, said Joanne Wuensch, an
analyst with BMO Capital Markets. “That assumes no growth, which
is ridiculous, so that is an extraordinarily conservative
number,” she said.

Proving efficacy can be a lengthy process. St Jude Medical’s
Amplatzer Occluder device, used to close a tiny hole in
the heart, is awaiting an FDA decision. The decisive U.S. trial,
which was not deemed complete until a pre-specified number of
patients suffered strokes or died, took eight years.

Eucomed is campaigning to keep in place the system that
brings new products to those markets earlier.

“As you get physician experience developing, you also start
immediately improving the product,” said Eucomed CEO Serge
Bernasconi. “That explains why by the time it gets to market in
the U.S., often in Europe we are already on the second or third
generation.”

Edwards, which considers the original Sapien valve to be
obsolete and manufactures it only for U.S. use, expects European
approval for its third-generation version by the end of 2013.

Meanwhile, U.S. doctors still await its predecessor.

(Reuters) – First Manhattan Company (FMC) added some heavyweight muscle on Thursday to its bid to shake up the board of drugmaker Vivus Inc (VVUS.O: Quote, Profile, Research, Stock Buzz) by naming former Carl Icahn top lieutenant Alex Denner and two others to its slate of proposed nominees.

Vivus shares rose as much as 11 percent after First Manhattan, which has nearly a 10 percent stake in Vivus, expanded its slate of proposed directors from six to nine, including Denner.

Denner, chief investment officer Sarissa Capital Management, has served on boards of biotechnology and other healthcare companies such as Biogen Idec (BIIB.O: Quote, Profile, Research, Stock Buzz) and ImClone Systems, later bought by Eli Lilly and Co (LLY.N: Quote, Profile, Research, Stock Buzz). Denner also is a founding partner of Sarissa, which owns about 2 percent of outstanding Vivus shares. Jumping into the Vivus proxy fight is one of his first public forays since starting his own fund.

“In every area that needs to be fixed we want to attract the highest quality human capital,” Sam Colin, senior managing director at FMC and a board nominee, said in a telephone interview.

The other two nominees added to the FMC slate are Rolf Bass, who has an extensive European pharmaceutical regulatory background, and Mel Keating, who has expertise in corporate turnarounds.

Asked about the choice of Denner, Colin said, “What we wanted first and foremost was someone with Alex’s track record.”

“There is no one else like Alex Denner. He’s not only incredibly intelligent, incredibly experienced, very thoughtful, he’s easy to get along with and very helpful in contentious situations where people’s emotions can get the better of them,” Colin said.

Denner had been head of healthcare investments for billionaire investor Icahn, and a regular on many of Icahn’s proposed director slates.

FMC, in a statement, called its slate of nominees a “clearly superior alternative to Vivus’ current board of directors,” adding that its nominees offer independence from management.

It has been agitating for change at Vivus since March over the company’s disappointing handling of the launch of its diet drug Qsymia, which won U.S. approval in September. Even with Thursday’s share gains, Vivus’ stock is worth half of what it was last July.

Another top investor, QVT Financial LP, had previously publicly said that Vivus should be sold. Analysts and other investors have been calling on Vivus to find a pharmaceutical company partner with deep pockets and a large sales force to help get Qsymia off the ground.

Vivus reported Qsymia sales of only about $4 million in the first quarter.

“They’ve got the right asset and the fix is having the right people behind the asset,” Colin said of Qsymia. “It should be a huge drug.”

Vivus’ board of directors is scheduled to be chosen at its annual shareholders meeting on July 15. Its shares closed up 7.2 percent at $14.50 and had climbed as high as $15.04 earlier.

(Reporting by Bill Berkrot; Editing by David Gregorio)

That could translate into lower-cost treatments for large unmet needs, such as pancreatic cancer, at precisely the time when pressure is mounting to reduce runaway healthcare spending.

Despite six drugs in clinical development – one of them in late-stage trials – and two more about to advance to human testing, Merrimack is burning only about $20 million a quarter.

“For the size and scale of what we do, that’s eye poppingly low,” Merrimack Chief Executive Robert Mulroy told Reuters.

“Our cost structure is orders of magnitude lower than anybody to date in this business. Our cost from starting a discovery program to getting into the clinic is less than $20 million, and the industry average is close to half a billion per molecule,” he said in an interview this week.

“Hopefully, we’re going to get to less expensive drugs because our capital costs to be successful with them will be so much lower.”

That would be music to the ears of payers and the overtaxed U.S. Medicare system contending with new cancer treatments that can exceed $100,000 per patient.

Started by six professors from Harvard and the Massachusetts Institute of Technology in 2000, Merrimack is nearing the finish line with what could be its first commercial product, a nanotherapeutic treatment for pancreatic cancer – a disease for which patients currently have few options.

Shares of Merrimack, which has a market value of about $500 million, are down nearly 16 percent this year, while the biotech sector overall has been on the rise.

Brean Capital analyst Gene Mack said investors have been wary about the prospects for the company’s lead drug because the failure rate for pancreatic cancer drugs has been high and Merrimack is testing its drug in patients that have failed prior treatment – a population with a very poor prognosis.

“Investors don’t realize how much progress has been made in the last year,” Mack said. “Fundamentally, this is my favorite company (worth) under a billion dollars.”

Late-stage trial data on the lead drug candidate, known as MM-398, is expected the second half of this year. If the study succeeds, the company could file for approval late this year or early in 2014.

MM-398 is designed to treat a particular type of tumor – hypoxic tumors – that tend to be resistant to standard therapies because of poor blood flow to the tumor.

“You don’t have a lot of highways to the tumor so you don’t get a lot of drug there,” Mulroy explained.

The Merrimack technology is designed to deliver cancer-killing therapy directly into the tumor and have it work for far longer than other new medicines that directly target tumors.

“Our technology keeps the drug in the tumor for over a week as opposed to just a few hours,” Mulroy said.

Hypoxic tumors are very common in pancreatic cancer, making it notoriously difficult to treat, but are also present in many other types of solid tumors.

Merrimack is developing a companion diagnostic test that uses a radioactive imaging agent to identify hypoxic tumors. If the test works as intended, MM-398 could also eventually treat lung, breast, colon and other cancers if patients are found to have the right type of tumor, giving it a huge potential market. The company plans to test MM-398 in combination with chemotherapies and targeted biotech medicines.

Merrimack also has a drug, MM-111, in Phase II testing for gastric cancer, for which there is an enormous unmet need, particularly in China and Asia.

The company has enough cash to fund its numerous clinical trials for the rest of this year and take MM-398 through to approval and commercialization, Mulroy said.

The company has full rights to seven of the eight drugs in clinical development and hopes to retain them for the U.S. and European markets while looking for partners to sell the medicines in other parts of the world, the CEO said.

French drugmaker Sanofi acquired global rights to the Merrimack drug MM-121, being tested in lung, breast and ovarian cancer. Merrimack, which will get milestone payments and royalties on future sales of the medicine, expects data from four Phase II trials of MM-121 later this year.

In another vote of confidence, Sanofi is the company’s second-largest shareholder with more than a 5 percent stake, according to Thomson Reuters data.

Merrimack’s share performance over the second half of the year will hinge on a steady flow of clinical data, with four Phase II studies and the pivotal Phase III on MM-398 expected to be reported in the coming months.

“There will be plenty of opportunities to show that the technology works,” Mulroy said. “We’re in a big transition year for us.”

(Reporting by Bill Berkrot; editing by Ed Tobin and John Wallace)