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Assuming only 30% of patients respond to Fampridine, and only half (I'm underestimating) of all MS patients in the US (400–450K) have some degree of walking disability, then about 60K patients would be candidates for treatment with the drug. Agree that use will be limited to patients with significant degree of disability in case the drug will get heavily blackboxed (risk of seizure).
NICE has this morning issued guidance saying that Avastin (bevacizumab), Nexavar (sorafenib) and Torisel (temsirolimus) are not recommended as first-line treatment options for advanced and/or metastatic renal cell carcinoma. In addition, the agency has turned down the use of Nexavar and Pfizer’s Sutent (sunitinib) as secondary treatment options for people with either form of the disease, adding that those patients who are currently receiving these treatments should have the option to continue their therapy until they and their clinicians consider it appropriate to stop.
http://www.timesonline.co.uk/tol/life_and_style/health/article6809869.ece
ACOR/Fampridine-SR
The author neglected a few important points IMO:
The drug has successfully completed two SPA-supported
phase III trials. In its 1st study it met all three predefined efficacy outcome measures. Its effect was seen in all four MS types (PPMS, SPMS, RRMS, PRMS).
The FDA granted the drug a priority review (Acorda had not requested that). So the FDA finds the drug to be addressing an unmet medical need, and/or being a significant improvement over the current SOC.
The drug has a long history of off-label use.
On a side note: a delay is likely since the FDA panel schedule to be on Oct. 14, too close to the PDUFA.
Unless new lots of the drug (Cerezyme) reach the market...
Part 2 of the study will start after RVR data from Part 1 are known, so dosing might change. Also, mgmt said it will not need to wait for full SVR results from part 2 before designing/starting phase III.
It took two teams 4 or 5 years to find the error out of about 2,000,000 base pairs searched.
Nice!
Another failure is Cephalon's sparlon, a high dose formulation of modafinil. The FDA issued a "non-approvable" letter and Cephalon has dropped development of the product.
Right. Now can you name one case that failed?
A twist to your quiz:
Companies have undertaken several franchise extension strategies to mitigate patent risk, including developing an alternative high dose formulation. Can you find an example for such strategy?
I find The Cystic Fibrosis Mutation Database very useful.
http://www.genet.sickkids.on.ca/cftr/app
Like this table of most common CFTR mutations and prevalence in populations(data based on the screening of 43,849 CF chromosomes).
http://www.genet.sickkids.on.ca/cftr/resource/Table1.html
VRTX/Cystic Fibrosis
VX-770 will be studied in patients bearing the G551D mutation on at least one allele (2 phase III trials), and also in homozygous for the higher prevalence F508del mutation (phase II trial). So VX-770 still has potential beyond G551D patients population.
On economic factors I have commented elsewhere (http://siliconinvestor.advfn.com/readreplies.aspx?msgid=25673345&nonstock=False&subjectid=7368) and I would add another potential benefit: it could lead to reductions in need for inhaled antibiotics and mucolytics.
Almost all patients with CF are either homozygous for F508del or compound heterozygous for two different CFTR mutations.
One interesting point I would note after reading the Nature paper is that the polymorphism associated with SVR, resides 3kb upstream of the IL28B gene, which encodes IFN-l-3, and so this could be important to ZGEN with their Peg-INF lambda candidate.
Btw, this work will be discussed at AASLD (saw a late breaker title of the Nature paper).
AASLD - late-breakers presentations/posters are out.
One more step towards personalizing EGFR tyrosine kinase inhibitors - screening for EGFR mutations in non–small-cell lung cancer:
Tests help lung cancer drugs reach right patients
http://www.reuters.com/article/rbssHealthcareNews/idUSN1949135120090819
By Julie Steenhuysen
CHICAGO, Aug 19 (Reuters) - Diagnostic tests that look for specific genetic or molecular characteristics may be the key to helping doctors decide which lung cancer treatments work best for patients, two studies released on Wednesday suggest.
In one, researchers found AstraZeneca's (AZN.L: Quote, Profile, Research, Stock Buzz) lung cancer pill Iressa, or gefitinib, worked far better than chemotherapy in people from East Asia whose tumors had specific mutations in genes for the epidermal growth factor receptor or EGFR.
In another*, a Spanish team found that people in Europe whose tumors also had mutations in the EGFR gene were more likely to be helped by Roche's erlotinib, brand name Tarceva, than other lung cancer patients.
Both studies, published in the New England Journal of Medicine, reinforce prior findings and offer new evidence that screening tests may be useful to match patients with the best therapy.
"Given the fact that the cost of these drugs is exceedingly high ... I think we have to use them in selective subtypes, the ones most likely to respond," Dr. Adi Gazdar of the University of Texas Southwestern Medical Center, who wrote a commentary, said in a telephone interview.
"If you can select out the right subtype, that is an important finding, and an important cost savings as well."
Gazdar said the findings in the East Asians were strong enough to suggest that Iressa might be effective as a first choice therapy for carefully selected patients.
IMPROVING ODDS
Drug companies and regulators increasingly are turning to so-called companion diagnostics -- tests that look for specific genes or proteins -- as a way to increase the odds a high-cost biotechnology drug will work in specific patients.
AstraZeneca stopped most U.S. sales of Iressa in 2004 after it was found to help only about 10 percent to 15 percent of lung cancer patients. But several studies have suggested that some people -- notably nonsmokers, Asians and women -- did better on Iressa.
In the latest study, Dr. Masahiro Fukuoka of Kinki University in Osaka, Japan, and Dr. Tony Mok of the Chinese University of Hong Kong and colleagues analyzed data on a group of 261 East Asians who had been nonsmokers or light smokers and whose tumors had the EGFR mutation.
Nearly 25 percent of people who had the mutations and who took Iressa survived a year without their cancer advancing, compared with just 6.7 percent of those who got chemotherapy.
Gazdar said while Iressa did not save any lives in the end, that may be because it is often not offered until other treatments failed. "I think they make a good case that it should be used as first-line therapy," he said.
For the second study, a team lead by Dr. Rafael Rosell of the Catalan Institute of Oncology in Spain screened more than 2,100 patients with non-small cell lung cancer for EGFR mutations.
Like earlier studies in East Asians, they found people who had the mutations were more likely to respond to Tarceva. And it showed that diagnostic testing for EGFR mutations can be done quickly, and on a large scale, Gazdar said.
"The evidence is building that there is potentially a particular benefit for the group of people who have EGFR mutations," said Charlotte Arnold, a spokeswoman for Genentech, now wholly owned by Roche.
She said Roche is conducting a late-stage study in Europe looking at the effectiveness of Tarceva as a first-line treatment for lung cancer patients with EGFR mutations. The study incorporates the use of a companion diagnostic test.
Tarceva, which costs about $3,600 per month, is already approved for lung cancer patients who have failed at least one round of chemotherapy.
Lung cancer kills 1.2 million people a year and is the top cause of cancer death globally.
*http://content.nejm.org/cgi/content/full/NEJMoa0904554
More of the same:
Does Teva have Shire in its cross-hairs?
http://www.reuters.com/article/innovationNews/idUSTRE57K2G020090821
By Ben Hirschler and Steven Scheer
LONDON/JERUSALEM (Reuters) - Teva Pharmaceutical Industries, the world's biggest generic drugmaker, could turn the tables on its Big Pharma rivals by snapping up Shire, a maker of branded specialty medicines.
That, at least, is the buzz among investors casting around for the next $10 billion-plus transaction in a sector that has seen a wave of deal-making this year.
Buying Shire would make sense for the acquisitive Israeli group, some analysts say, since Teva is looking to shore up its relatively small, yet important, branded business as its multiple sclerosis drug Copaxone faces the threat of generic competition.
Shire, which operates out of Britain and the United States but is based in Dublin for tax purposes, could fit the bill.
Healthcare bankers familiar with the two companies said Shire was an attractive target for Teva, and potentially others, given its line-up of marketed and experimental drugs in specialty medicine, but a deal did not appear to be imminent.
A bid for Shire, which would have to be pitched at well over $10 billion, would be a record size for Teva and might be too much of a stretch, one added.
Officials at Teva and Shire declined to comment.
"It's aggressive but Teva has bought large companies before. They have showed a lot of skill in digesting large companies," said Gilad Alper, an analyst at the Excellence Nessuah brokerage in Tel Aviv.
"Shire would be more complicated since it's branded and not generics and marketing would be different -- but it would not be overly ambitious."
Teva, which bought Barr for $7.5 billion in 2008, certainly has a track record of doing major acquisitions and said last month it was ready to look outside of generics for future deals.
"We believe that the same type of capabilities that we have developed in the generic markets, we can also apply to specialty," Teva's North American CEO Bill Marth told analysts during the company's second-quarter conference call.
"Now, this doesn't mean that Teva is going to necessarily run out tomorrow and chase down specialty companies ... but ... as you think of companies moving forward, you should not limit your thinking to just generic companies."
BLURRED DIVISION
A Teva-Shire deal would mark a further blurring of the dividing line between branded and cheaper generic medicines at a time when big drugmakers like Pfizer and GlaxoSmithKline are increasingly moving into the generic space. Citigroup analyst John Boris is convinced acquiring Shire would make strategic and financial sense for Teva.
In a note last week he estimated a deal closing by end-2009 would be modestly dilutive in 2010 and accretive to earnings thereafter, assuming Teva paid the same 40 percent premium as for Barr and offered 40 percent equity and 60 percent cash.
With Shire's market value at $9.3 billion that would imply a price of $13 billion. But Excellence's Alper thinks the premium might not be so large, given a recent rally in Shire shares.
Teva's market capitalization is $46 billion.
Bringing Shire into the fold would make Teva a major player in hyperactivity drugs -- it already sells a generic version of Shire's Adderall XR treatment -- and add a range of drugs for rare diseases that Shire picked up by buying TKT four years ago.
Shire is relatively rare beast, since it is one of the few mid-sized drugmakers in Europe that is available to be bought and not held by a family trust.
As a result, it is often in the rumor mill. Previous suggested buyers have included British rivals AstraZeneca and Glaxo.
But Shire also has the firepower to make a chunky acquisition itself and Ian Wainwright, an analyst at Canaccord Adams, thinks a bid for the likes of Swiss biotech group Actelion could be a potential defensive move.
FWIW, I thought that PG’s will to go for a 2nd generation product, despite Intrinsa's troubles, is positive for BPAX as it provides validation of the market. So the fact that the program is "on hold" and PS doesn't talk about it, might not be a good indicator.
I think that off-label use of branded or generic “male” products is less of a worry than Paragraph-IV challenges against LibiGel.
On generic challengers to Libigel - they might appear if the market is there.
PG/NOVN 2nd gen patch for HSDD
Perhaps Intrinsa's sluggish sales in Europe and a questioning view have helped PG to put their 2nd gen patch for HSDD on hold
http://www.reuters.com/article/marketsNews/idAFL260089620090303?rpc=44
PG/Intrinsa, BPAX
Don't think anyone has mentioned the fact that PG signed a license agreement with NOVN for a 2nd generation transdermal patch for HSDD, think about a year ago.
No one mentioned this but as of late, Frost is selling big chunks of his holding and so did Dr. Aviezer before him with his smaller amount of shares (they all have their reasons for selling but knowing Frost I bet Aviezer's transactions and his are related to some degree):
http://finance.yahoo.com/q/it?s=PLX
Tanner a Lazard analyst, upgraded shares of Shire to "Buy" from "Hold," saying that shortage of Genzyme's drug Cerezyme could boost sales of a rival treatment. He now expects sales of velaglucerase [Shire's ERT] to reach $124M in 2010, up from a previous estimate of $12M, and he now forecasts $325M in revenue in 2011, and $407M in 2012. Tanner said he discussed the situation with a physician who believes only about 300 to 400 patients will be able to stay on Cerezyme. Unless new lots of the drug reach the market, he said, about 500 more will need a different treatment [some may choose drug holiday], and they might continue using other drugs even after Cerezyme supplies are restored [assuming expanded access is available through approval]. Tanner pared his price target on Genzyme shares to $64 per share from $71. He said the company put sales of Cerezyme and another drug, Fabrazyme, at risk by making them in the same facility as a newer product, Myozyme. The company may scrutinize the decisions of its executives as a result [GENZ already decided to no longer produce Myozyme/Lumizyme at the 2000L scale in the Allston facility.]
http://www.thestreet.com/story/10578340/1/ahead-of-the-bell-gaucher-disease-treatments.html
My remarks are in Italics
GENZ, Shire, PLX
Tanner a Lazard analyst, upgraded shares of Shire to "Buy" from "Hold," saying that shortage of Genzyme's drug Cerezyme could boost sales of a rival treatment. He now expects sales of velaglucerase [Shire's ERT] to reach $124M in 2010, up from a previous estimate of $12M, and he now forecasts $325M in revenue in 2011, and $407M in 2012. Tanner said he discussed the situation with a physician who believes only about 300 to 400 patients will be able to stay on Cerezyme. Unless new lots of the drug reach the market, he said, about 500 more will need a different treatment [some may choose to go on drug holiday], and they might continue using other drugs even after Cerezyme supplies are restored [assuming expanded access is available through approval]. Tanner pared his price target on Genzyme shares to $64 per share from $71. He said the company put sales of Cerezyme and another drug, Fabrazyme, at risk by making them in the same facility as a newer product, Myozyme. The company may scrutinize the decisions of its executives as a result [GENZ already decided to no longer produce Myozyme/Lumizyme at the 2000L scale in the Allston facility.]
http://www.thestreet.com/story/10578340/1/ahead-of-the-bell-gaucher-disease-treatments.html
My spellchecker wanted to replace Extavia with Octavia!
NVS' first MS drug approved in the US as well: Extavia - an interferon beta-1b
http://triangle.bizjournals.com/triangle/stories/2009/08/17/daily5.html?ana=yfcpc
PLX share price did go up since GENZ announced on 6/16 that the Allston facility, would be shut down temporarily due to virus contamination. Implications are that docs and patients can get familiar with both drugs from PLX and Shire before commercial approval. This should only last a couple of months with no direct economic benefit but it is a good PR on GENZ's expense.
PLX and Shire as well will provide their drugs free of charge during the Cerezyme supply shortage. They can only charge for the drugs after approval.
D-Pharm Raises $23M through Rights Offering and IPO
http://www.genengnews.com/news/bnitem.aspx?name=60708902&source=genwire
Israeli company D-Pharm raised NIS 85 million (about $23 million) through a combined oversubscribed IPO that secured some NIS 28 million and a rights offering of NIS 57 million. The company says that it’s premoney valuation was about NIS 120 million (approximately $31.54).
Most of the funds will be used for a pivotal Phase III trial of D-Pharm’s DP-b99, which is in development for the treatment of acute ischaemic stroke. FDA cleared the IND application for the Phase III MACSI trial in June. The study will include about 770 patients with moderately severe ischaemic stroke in clinical centers in North America, Europe, South Africa, and Israel.
DP-b99 is a neuroprotective, membrane-active chelator derived from the known calcium chelator BAPTA. Administration of the drug is supposed to start within nine hours of stroke onset. Previously reported data from a Phase IIb trial with DP-b99 showed treatment with the drug doubled the percentage of patients that completely recovered from ischaemic stroke.
D-Pharm says that it also intends to investigate the drug’s potential in the treatment of traumatic brain injury and for prophylactic treatment of neurological damage associated with coronary artery bypass graft procedures.
DP-b99 was developed using D-Pharm’s Membrane Activated Chelator (MAC) technology, which hinges on the use of lipids to develop small molecule drugs that function only within the lipid environment of cell membranes. MAC drugs are essentially switched off in hydrophilic environments such as blood plasma, extracellular fluids, and cytoplasm and switched on in lipophilic environments. D-Pharm claims this property means MACs can be developed as highly potent and safe medicines for the treatment of pathological processes precipitated by abnormal ion distribution thereby preventing cell apoptosis.
Commenting on the combined fundraising, D-Pharm’s board chairman, Ruben Krupik, says, “This is a unique offering because the current shareholders provided most of the financing. We gave the public the opportunity to participate, while taking most of the risk upon ourselves.”
CEO, Alex Kozak, Ph.D., adds, “I am happy to see the Israeli public sector investors supporting an advanced clinical-stage company like D-Pharm. I hope that our IPO opens the door to the flotation of other companies, especially in the biotech industry.”
D-Pharm’s pipeline includes DP-VPA, a derivative of the antepilepsy drug, valproic acid (VPA). Developed using the company’s RAP™ technology, DP-VPA has already completed a Phase II trial in patients with complex partial epilepsy. The RAP platform involves chemically linking a lipid vector to the active site of a drug.
This creates an inactive prodrug that is only activated at the site of disease when disease-specific enzyme activity cleaves off the lipid vector. D-Pharm believes that the application of its D-RAP™ Technology has allowed the development of a better VPA candidate, with all the utilities of the parent drug but an improved safety profile. DP-VPA is also in development for the treatment of bipolar disorder and for migraine prophylaxis.
Well, with Market Cap above 441M I don't consider it "too cheap", but I certainly see more upside.
And the stock is currently up 14% here at TASE in a very red day.
I attend their presentations once in a while and the one at Canaccord dids not differ much except the joke about calling prGCD 'carrotzyme', sounds better in Hebrew. Only new detail I noticed here was Aviezer's comment on the switching study, which enrolls much faster now due to the Cerezyme shortage.
I don't have new insights, they are all old
There are several potential upside drivers for 2009 regarding PLX itself: IRB approvals, phase III data are expected in Oct. and an NDA submission by year-end (only next year in EU), commercial collaboration for prGCD could also occur soon. External factors - we didn't yet see full data from Shire and any hiccup there may be positive for PLX. Same goes for the Cerezyme shortage.
I didn't scare him away, quite the opposite - I've resigned from the assistants position when he became the moderator.
Yeah, 'ridin lightning' is a dangerous business indeed. We never do that down here, our obligatory military service is hazard enough...
Ok, after seeing your excited statement twice, I'll take your word for that, so no need to post it for the 3rd time
Current leaders of next-generation sequencers are:
1. Genome Analyzer (Illumina/Solexa)
2. SOLiD system (LIFE/ABI)
3. 454 Life Sciences (Roche)
As far as I can tell Genome Analyzer is a clear leader in academic laboratories which are the dominant costumers here. Affymetrix is the strongest player in the gene expression area (array) and a new complaint filed by ILMN on May 4 targets AFFX' HT array plate and scanner products including the recently launched GeneTitan System.
GILD is laying off up to 66 people as it closes its offices in Boulder and Westminster, Colorado, US to consolidate its operations in California.
http://sanfrancisco.bizjournals.com/sanfrancisco/stories/2009/08/10/daily66.html?ana=yfcpc
Europe prepares for drugs from GM plants
http://www.nature.com/news/2009/070809/full/news.2009.630.html
Guidelines for pharmed medicines compare favourably with US rules.
By Natasha Gilbert
Commercial development of plant-derived pharmaceuticals has moved forward today with the publication of the first European guidelines for growing these genetically modified (GM) plants.
Drawn up by the European Food Safety Authority (EFSA), based in Parma, Italy, the guidance describes how developers of GM plants grown for purposes other than human or animal consumption, such as producing pharmaceuticals or industrial enzymes, will need to assess the potential risks to humans, animals and the environment.
An EFSA risk assessment will be required when developers seek commercial approval to grow the plant. The evaluation will be passed on to the European Commission and member states, which decide whether to grant permission. In contrast, scientists wishing to grow GM crops for research purposes need only apply for a licence in the individual member state in which they wish to grow the crop.
On your marks
Reinhilde Schoonjans, scientific officer on the EFSA's Scientific Panel on Genetically Modified Organisms, says the agency has not yet received any applications for plants modified to produce drugs. Internationally, only a handful of clinical trials of such drugs are under way, and there are no plant-pharmed drugs on the market. But, Schoonjans says, the technology is progressing fast and the EFSA is now in a position to receive applications — likely to come mostly from university spin-offs. "We want to be ready," she says.
The EFSA will only consider the risks of growing the GM plant. The safety of the plant's product will be considered by the European Medicines Agency (EMEA), which has guidelines on the safety and quality requirements of plant-derived drugs that came into effect in February.
Under the EFSA guidance, developers must detail the biological differences between the GM plant and the conventional crop it is derived from and how these affect the plant's function and growth. They also have to assess the risk of engineered genes being passed on to other plants and any danger posed to humans or animals who accidentally eat the transgenic crops.
Applicants must also specify the measures they will take to monitor the plants and protect against exposure — such as warning signs, fences and sterilization of the plants to prevent them reproducing.
Strict rules
"It replaces what we had before, which was nothing, so that is a positive step," says Julian Ma, a molecular immunologist at St George's Hospital Medical School, University of London, who helped to draw up the guidelines.
He says that the guidelines are based on existing GM-food regulation, which imposes strict rules on managing unintended effects from GM plants. These rules are not mirrored in conventional agriculture, where there are also unintended effects, Ma says.
For instance, there is "no scientific rational" for requiring the rigorous testing of a plant genetically modified to produce a toxic substance, Ma says, but not requiring the same tests of a plant bred through traditional methods to produce the same toxic compound. "We struggled with this," he says.
Jeffrey Wolt, an expert in plant biotechnology risk assessment at Iowa State University in Ames, approves of the European guidelines and says they are consistent with those set out by the US Food and Drug Administration and Department of Agriculture.
He is pleased that the guidelines will consider each application on a case by case basis. "This is critical," he says, "because when you are working with an emerging area of science such as this, a too prescriptive process would be counter productive."
Corrected:
EFSA is the European Food Safety Authority, not the European Food Standards Agency as stated in an earlier version of this article.
Another hypothesis to explain why schizophrenics have low incidents of cancer - medications. My gut feeling is that there is a genetic link between the schizophrenia gene and anti cancer genes that gives some kind of compensation for the mental illness by extra strength of the immune system. An even simpler reason is that schizophrenics don't leave long enough. Whatever the mechanism is, I am glad people start to notice these correlations. Usually, they stick to the dogma and look under the lamp. But maybe because the well is drying they are really starting to look everywhere more critically.
Anti-psychotic drugs could help fight cancer
http://www.eurekalert.org/pub_releases/2009-08/uons-adc081109.php
The observation that people taking medication for schizophrenia have lower cancer rates than other people has prompted new research revealing that anti-psychotic drugs could help treat some major cancers.
A preliminary finding in the current online issue of the International Journal of Cancer reports that the anti-psychotic drug, pimozide, kills lung, breast and brain cancer cells in in-vitro laboratory experiments.
Several epidemiological studies have noted the low rate of cancer among schizophrenic patients. These studies found, for example, that these patients have lower rates of lung cancer than other people, even though they are more likely to smoke.
Genetic factors and the possibility of reduced cancer detection in patients have been considered and over the past decade anti-psychotic drugs have been suggested as possible mediators of this effect.
In the new study, pimozide was the most lethal of six anti-psychotic drugs tested by a team from UNSW and the University of Queensland. Rapidly-dividing cancer cells require cholesterol and lipids to grow and the researchers suspect that pimozide kills cancer cells by blocking the synthesis or movement of cholesterol and lipid in cancer cells.
Analysis of gene expression in test cancer cells showed that genes involved in the synthesis and uptake of cholesterol and lipids were boosted when pimozide was introduced.
To test the idea that pimozide acts by disrupting cholesterol homeostasis, the researchers combined pimozide with mevastatin, a drug that inhibits cholesterol production in cells. The two drugs were more lethal in combination against cancer cells than when either drug was used alone.
"The combination of pimozide and mevastatin increased cancer cell death," says UNSW researcher Dr Louise Lutze-Mann, a co-author of the study. "We needed a lower dose of each drug to kill the same amount of cells."
Although side-effects are associated with the use of high doses of these drugs – such as tremors, muscle spasms and slurred speech – these effects are considered to be tolerable in patients where other treatments have failed and the drugs will only be used short-term. These side-effects would be reduced if the drugs were used in combination with a lipid-lowering drug, such as mevastatin.
The researchers have also investigated the effects of olazapine , a "second-generation" antipsychotic drug, and found that it also kills cancer cells but has a better side-effect profile. When administered to patients, it accumulates in the lung, which suggests that it may prove to be most useful in treating lung cancer.
The researchers are now testing these drugs on tumour cells from brain cancers since these tumours are extremely difficult to treat and are frequently associated with poor patient prognosis. Patients diagnosed with glioblastoma, for example, survive less than one year.
The results are very promising as these drugs are greater than 50-fold more effective at killing glioblastoma cells than the chemotherapeutic drug currently in use. The researchers are also investigating the effects of these drugs on cells derived from drug-resistant childhood cancers where current chemotherapy has failed.
Another hopeful prospect is an investigation of another group of drugs, called SERMs, which are similar in structure to the antipsychotic drugs but have far fewer side-effects associated with them.
FDA wants input on Amgen bone drug risks
http://www.reuters.com/article/marketsNews/idAFN1135758320090811?rpc=44
* Panel asked to weigh serious infections, cancers
* Analysts expect panel to back denosumab
* Advisory panel to review drug Thursday
* Amgen shares gain 2.56 percent (Updates share price)
By Lisa Richwine
WASHINGTON, Aug 11 (Reuters) - Serious infections and cancers must be considered as U.S. advisers weigh the future of Amgen Inc's (AMGN.O: Quote, Profile, Research, Stock Buzz) most important experimental medicine, drug reviewers said in documents released on Tuesday.
Shares of the world's largest biotechnology company rose 2.56 percent to close at $62.81 on Nasdaq. Analysts said the safety issues were known to investors and they expected an advisory panel to recommend approval of the drug, denosumab.
Amgen is seeking U.S. Food and Drug Administration approval to sell the injection under the name Prolia in an $8 billion market for osteoporosis drugs.
The company's studies raised questions about the risk of serious infections, new cancer cases and other problems seen in denosumab patients, FDA reviewers said in a memo prepared for an advisory panel review on Thursday.
"Of particular concern, in light of these safety issues, is whether the risk/benefit balance for the osteoporosis prevention indication, both for patients with and without cancer, supports approval," FDA staff said.
BMO Markets analyst Jason Zhang said the safety issues were "not surprising" and he felt the panel likely would vote in favor of the drug. Zhang expects denosumab to garner annual sales of $2.4 billion by 2012.
"People always worry about cancer and malignancies, but when you look at the incidence (with denosumab), you can't really have statistical analysis because they are so rare," he said.
Zhang also said investors may be comforted by the fact that FDA reviewers did not recommend a strict risk management program for the drug.
Cowen & Co analyst Eric Schmidt said the FDA documents "read fairly cautiously" and "it doesn't seem like the FDA has yet made up its mind about the risk/benefit of the drug."
He said he expected the panel would recommend approval, echoing the general consensus of other analysts. A pressing uncertainty is whether the panel will recommend a risk management program (REMS) or other potential warnings.
"If a stringent REMS program were required here, the stock could be down $3 or $4 on that," Schmidt said.
Denosumab is seen as the best hope of jump-starting Amgen's growth after safety concerns deflated sales of its flagship anemia drugs.
Amgen shares were trading nearly 40 percent above their year low of $44.96 at the end of April, but remain sharply down from the $80-plus level reached in late 2005.
Amgen is aiming to sell denosumab for treating and preventing the bone-thinning disease osteoporosis in women past menopause, and for treating and preventing bone loss from hormone ablation therapy for breast or prostate cancer.
Denosumab is the first in a new class of genetically engineered proteins that target RANK ligand, a protein that activates bone-destroying cells.
Amgen's studies showed the drug reduced fractures and increased bone density. FDA reviewers said that benefit must be weighed against an increased risk of serious skin infections, particularly in the setting of osteoporosis prevention.
Skin infections leading to hospitalization occurred in 0.4 percent of women given the drug for osteoporosis, compared with 0.1 percent who got a placebo.
Women in the osteoporosis studies also had a "slightly increased incidence" of breast, pancreatic, gastrointestinal and reproductive cancers, FDA staff said.
Amgen is banking on its clinical results as well as a patient-friendly dosing schedule of twice-yearly injections to help it compete with other osteoporosis drugs, including low-cost generics. Denosumab reduced the risk of spine fractures by 68 percent.
"The overall safety and efficacy of denosumab offer a meaningful alternative to existing therapies," the company said in a summary prepared for the advisory panel.
The agency usually follows panel advice when making final approval decisions. A ruling is due by Oct. 19, but the agency has missed several drug deadlines in the past year.
Denosumab would compete with osteoporosis medicines such as Novartis AG's (NOVN.VX: Quote, Profile, Research, Stock Buzz) Reclast, Actonel from Sanofi-Aventis (SASY.PA: Quote, Profile, Research, Stock Buzz) and Procter & Gamble Co (PG.N: Quote, Profile, Research, Stock Buzz), and Boniva from Roche Holding AG (ROG.VX: Quote, Profile, Research, Stock Buzz) and GlaxoSmithKline PLC (GSK.L: Quote, Profile, Research, Stock Buzz).
Global sales of osteoporosis drugs hit about $8.4 billion in 2008, according to data from IMS Health.
Glaxo made a deal with Amgen in July to sell denosumab in Europe and emerging markets for osteoporosis.
Carried into facility by humans?