Roche has tipped investors on all the key talking points ahead of today’s pipeline review. In a statement released early today, Roche noted that it is positioned to launch six new therapies by the end of 2014 and wants to push beyond cancer therapies and into new arenas, such as metabolism, inflammation and the central nervous system. And it has the potential to add 35 new indications for currently-approved therapies over four years.

Roche’s scientists believe that the pipeline currently includes 10 new molecules with the potential to emerge as a best-in-class therapy. And the company says that it can move 20 programs into late-stage trials by 2015.

Among its top prospects, Bloomberg highlights: Taspoglutide, a new GLP-1 drug for Type 2 diabetes; Aleglitazar, also for diabetes; The ‘good cholesterol’ drug dalcetrapib and PLX4032 for melanoma. All are believed to have solid blockbuster potential.

While Roche’s income from oncology drugs failed to live up to expectations recently, its near-term revenue is pinned on three key blockbusters: Avastin, MabThera and Herceptin. Analysts also credit Roche with being in a far better position than most other Big Pharma outfits, with enough time to develop new products that can boost revenue ahead of any key patent losses. Today’s pipeline show is designed to convince investors that it has that task well in hand.

Source: FierceBiotech

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Roche investors are expected to pay particularly close attention at tomorrow’s pipeline review day, when top execs for the pharma giant will try to put the best face possible on its new drug prospects.

This is the first pipeline review since Roche absorbed Genentech, and analysts will be looking to see whether the pharma giant’s recent minor setbacks with programs like the rheumatoid arthritis drug ocrelizumab can be overshadowed by the promise presented by its new biotech arm and a slate of potential blockbusters. Unlike most of its Big Pharma competitors, Roche doesn’t face a big patent cliff. And that has helped bolster its stock price. Now the analysts want to know how well positioned Roche is for the future.

“Investor expectations are high for this event and Roche does not have much margin for error, given the series of minor setbacks recently and the disappointment on 2009 sales,” Natixis analysts said in a note.

The Genentech acquisition, though, is so recent that it’s hard to see how Roche can blow it at this stage. Drug development is a notoriously slow process, and that gives Roche plenty of breathing space for completing the absorption process without much critical heat. So you can expect most of the attention to center on Roche’s three late-stage blockbuster programs: dalcetrapib, aleglitazar and RG1678.

Source: FierceBiotech

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The pressure’s on at Roche. Some months into its full ownership of Genentech, Roche has seen a couple of setbacks in its development program for that “pipeline-in-a-drug,” Avastin. Will it fare any better with its future efforts to broaden Avastin use? Can it win new indications for Avastin’s fellow cancer med Herceptin? What about Rituxan/MabThera?

Executives will seek to quell any fears about these efforts at a meeting Thursday. Analysts are looking for reason to believe, the Wall Street Journal reports. “Roche will have to prove that with the takeover of Genentech it can turn into a real leader in pharma and biotechnology,” Zuercher Kantonalbank analyst Michael Nawrath told the paper. “[I]t needs to prove it can produce growth out of these candidates.”

New indications are important for Avastin, Herceptin and Rituxan to keep those three key meds growing; after all, they represent more than one-third of the company’s sales. Analysts will be looking for info on how much Roche expects these three drugs to grow–this year and as time goes on. The company will also talk about its experimental drugs. Stay tuned later this week for an update.

Source: FiercePharma

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The FDA says it added its strongest warning today to the label of the widely used bloodthinner Plavix, Bristol-Myers’ best-selling drug, to help physicians treat patients correctly. But the warning could make doctors’ job more difficult.

Docs prescribe Plavix to reduce the risk of heart attacks, strokes and other serious heart problems. The drug prevents dangerous blood clots that can cause those conditions. As a growing number of studies has demonstrated, however, Plavix doesn’t work well in certain patients – those with a genetic variation that makes it difficult for them to metabolize the drug.

The FDA says between 2% and 14% of Plavix users don’t respond well to the drug and might benefit from alternative treatment. Hence the new so-called black-box warning.

Genetic testing could identify the poor responders. But most doctors aren’t well equipped to do genetic testing. They don’t have quick access to the tests. Even if they did, they might not have time in the cases of many patients to wait for results to come back.

What’s more, the FDA has approved only one genetic test, Roche’s AmpliChip, to look for the variation, but not specifically for determining treatment with Plavix. Many laboratories offer other tests, whose quality the FDA says doctors will have to assess before using. Doctors should make sure the tests are at least 98% accurate, FDA officials told reporters.

Christopher Cannon, a Harvard Medical School associate professor and editor-in-chief of Cardiosource, tells the WSJ’s Ron Winslow that heart-doctor associations will need to develop protocols for testing and treatment. The alternatives include increasing the dose of Plavix or switching to bloodthinner Prasugrel from Lilly and Daiichi Sankyo, but Cannon says neither has been tested for that purpose.

“Thus a real conundrum” for patients and their physicians, Cannon said. “I expect mass confusion in response to this FDA warning,” he added.

Plavix, which is also marketed by Sanofi Aventis, is the second-best selling drug world-wide with $8.6 billion in sales in 2008, according to IMS Health.

Source: The Wall Street Journal

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Roche and Genentech’s anticancer drug Avastin failed to meet its primary endpoint in a Phase III trial involving 1,000 men with late-stage hormone-refractory prostate cancer (HRPC). The Cancer and Leukemia Group B study 90401, sponsored by the NCI, found adding the antiangiogenesis drug to chemotherapy and prednisone had no benefits on overall survival.

The disappointing Avastin results follow less than a week after sanofi-aventis reported positive data from a Phase III trial with its HRPC candidate. The study showed that adding cabazitaxel to prednisone improved overall survival and boosted progression-free survival in patients whose disease had progressed following treatment with docetaxel-based chemotherapy. The TROPIC trial compared a combination of cabazitaxel and prednisone with mitoxantrone plus prednisone.

Roche has been undergoing something of a late-stage trial results rollercoaster over the last few weeks. The negative prostate cancer trial data comes less than a month after the firm reported positive data from a Phase III study with Avastin against ovarian cancer. This trial demonstrated that maintenance therapy with Avastin following surgery and chemotherapy significantly boosted progression-free survival. Just the day before that, however, the company reported late-stage trial data that showed adding Avastin to chemotherapy in patients with advanced or metastatic/inoperable gastric cancer had no benefits on overall survival.

Safety also appears to remain an issue with Avastin. While detailed assessments from the latest prostate cancer study are ongoing, Roche confirmed that the preliminary data flagged the same severe adverse events observed in other pivotal Avastin trials, including neutropenia and fatal infections.

Avastin is not the only Roche drug demonstrating safety concerns. The late-stage antibody Ocrelizumab has also been linked with serious and sometimes fatal treatment-related opportunistic infections. The humanized anti-CD20 mAb is being developed in partnership with Biogen Idec, and just last week the companies confirmed that they were halting Ocrelizumab Phase III development for rheumatoid arthritis due to safety issues. Trials with Ocrelizumab in lupus nephritis patients had previously been stopped for the same reasons, although Phase II trials in patients with multiple sclerosis are ongoing, the companies noted.

The safety issues must have come as a serious blow to Roche and Biogen Idec. In December 2009, the companies had reported positive data from the first Phase III trial of ocrelizumab in RA, which showed that combining the drug with methotrexate significantly improved signs and symptoms of the disease.

Safety issues aside, Avastin, is remains Roche’s biggest-selling pharmaceutical. It achieved total sales of over CHF 6.2 billion (about $5.9 billion) in 2009, up 21% on 2008. Sales of the drug represent 16% of all Roche’s pharmaceutical division sales in 2009. It is currently approved in the U.S. and Europe for treating advanced colorectal, gastric, non-small-cell lung, and kidney cancers. In Japan approvals currently cover the advanced colorectal and non-small-cell lung cancer indications.

Avastin is also approved in the U.S. for the treatment of patients with advanced glioblastoma, although the European Agency’s Committee for Medicines for Human Use gave a negative opinion on approval of the drug for this indication in December 2009. The European filing was based on the same trial data used for the U.S. submission.

According to Roche, both investigator-led studies and a large-scale Phase III trial in over 900 patients with newly diagnosed glioblastoma multiforme are now under way. During 2009 a regulatory filing was also made in Switzerland for the relapsed glioblastoma indication and submissions were separately filed in the EU, U.S., Japan, and Switzerland for the use of Avastin in combination with standard chemotherapy in the first-line treatment of metastatic breast cancer.

In its 2009 annual report Roche stated that over 450 trials involving some 40,000 patients are currently investigating the use of Avastin in about 30 different tumor types.

Source: GEN News

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It’s hard to get precise figures of how many people have been taken off the payroll at pharma and biotech companies recently. According to staffing firm, Challender, Gray and Christmas, the combined industries shed 58,969 jobs in the first nine months of 2009, 15,000 more than the whole of 2008. In total, that makes around 74,000 redundancies in just 21 months, many but not all of which came from sales forces. Figures from FiercePharma, meanwhile, show just ten companies saw 66,850 jobs go in 2009. And this doesn’t include layoffs from the merger of Roche and Genentech, nor the 860 jobs that were announced at Boehringer Ingelheim in August.

They could do worse than follow the example of Medivation, a Californian company that has more than doubled its workforce, albeit from an extremely low base, from 28 in 2007 to 59 in 2008. Founded by a group of experienced professionals, its business model tries to bridge the gap between early-stage development and product launch. It finds promising compounds in markets with significant unmet needs, adds a bit of value and then sells them on to big pharma in record-breaking deals. In that sense, it is doing precisely what a team of analysts at Morgan Stanley said in January that Big Pharma should be doing, moving away from internal R&D and focus more on in-licensing. To move, in other words, from research and development to search and development.

While well-argued, it is not a particularly original proposal and forecast data from EvaluatePharma shows that while Big Pharma is certainly up for in-licensing, it is also not that keen to give up its central defining activity. Indeed, it is actually spending more on internal R&D as a percentage of sales. In 2008, it spent $69.8 billion, a figure that had grown by 9.3% annually since the turn of the century. And while it is set to slow quite radically to 1.5% CAGR from 2008–2014, when expressed as a percentage of sales, the figure is actually rising, from 15.6% in 2000 to an expected 18.5% in 2014.

Medivation, meanwhile, has done spectacularly well from buying in and partnering on. It had just two pipeline candidates in 2008, both of which have since been bought up by Big Pharma in record-breaking deals. The first was in September 2008, when a $225 million upfront fee from Pfizer for its Alzheimer’s candidate Dimebon was the largest for a single pipeline product that year. The second, in October 2009 with Astellas Pharma, brought in another $110 million upfront for the prostate cancer drug, MDV3100. That was the fourth largest upfront fee in 2009.

A reason for its success may be to do with its size and focused business development team that would confirm another suggestion on how pharma might revamp its ailing R&D model. This comes from the consultancy firm McKinsey & Co, which brought out a report in February that said scientific innovation is only part of pharma’s R&D problem. Better management could also play a part. “Increased attention to costs, speed of development and decision making,” it said, “could increase the internal rate of return (IRR) of an average small molecule from around 7.5% — less than the industry’s cost of capital — to 13%.”1

Without knowing the IIRs on Dimebon and MDV3100, investors are certainly impressed. Shares in this small company initially rose to $27.92 after the deal with Astellas Pharma, giving the company a market capitalization of $935 million, which is not bad for an outfit that has a payroll of just 59 and demonstrating there is life after Big Pharma.

Reference
1. The Road to Positive R&D Returns, Eric David, Tony Tramontin and Rodney Zemmel, McKinsey & Co Pharmaceutical and Medical Products Practice, February 2010.

Source: PharmTechTalk

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BioInvent International and Human Genome Sciences (HGS) are teaming up in a mAb collaboration focused on targets identified by HGS. The partnership will focus initially on inflammation.

BioInvent will use its antibody discovery technology to generate and develop mAb candidates. The deal gives both partners the right to participate in development and global commercialization of each antibody. They will share research, development, manufacturing, and commercialization costs as well as revenues.

The partnership with BioInvent represents the latest step in the HGS New Targets Initiative. The firm says following a careful review of its therapeutic and diagnostic targets, it has selected some targets for further research and potential development, both in-house and through research collaborations.

Bioinvent says its antibody discovery platform, n-CoDeR, comprises over 20 billion human antibody genes to significantly increase the likelihood of identifying antibodies with both high affinity and specificity against a particular target. Each antibody has a combination of complementarity determining regions (CDRs), which were originally isolated from the antibodies of a large number of healthy volunteers.

The n-CoDeR technology uses a process to recombine the CDRs into new antibody molecules. BioInvent claims that this allows the library to contain a wider variety of antibodies than could have been created naturally by the human immune system. Two library formats exist, one containing the smaller scFv antibody fragment and the other containing the Fab antibody fragment.

“BioInvent and HGS’ research strengths are both complementary and synergistic,” remarks Svein Mathisen, BioInvent’s CEO. “We believe this collaborative agreement is a strong and valuable way of building our pipeline of innovative drugs.”

The firm has four antibody products in clinical development. TB-402 is a thrombosis candidate being developed in partnership with ThromboGenics. The antibody is currently in Phase II trials. TB-403 is an oncology compound partnered with ThromboGenics and Roche that has completed Phase I trials. The atherosclerosis candidate BI-204 has also completed Phase I development and is partnered with Genentech. BI-505 is an in-house oncology candidate currently undergoing Phase I evaluation.

Source: GEN News

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Roche and Biogen Idec announced their decision to suspend Ocrelizumab treatment of patients in the Rheumatoid Arthritis (RA) programme. The decision follows the recommendation of the independent Ocrelizumab RA & Lupus Data and Safety Monitoring Board (DSMB) based on their assessment of the studies in RA (SCRIPT, FEATURE, FILM and STAGE) and lupus (BELONG and BEGIN).

The DSMB concluded that the safety risk outweighs the benefits observed in these specific patient populations at this time. The DSMB review detected an infection related safety signal which included serious and opportunistic infections, some of which were fatal.

As previously announced, the FILM study in MTX-naïve RA patients was placed on clinical hold following an assessment of benefit to risk in this specific RA patient population. In addition, the BELONG study in lupus nephritis patients was previously halted due to serious and opportunistic infection signals.

“Patient safety is of the utmost importance in all of our drug development programmes. In light of the DSMB recommendations we have decided to suspend Ocrelizumab treatment in the RA clinical development programme.” said Hal Barron, MD Executive Vice President and Chief Medical Officer at Roche.

The SCRIPT trial in patients who inadequately responded to one or more TNF antagonists and the FILM trial remain blinded. A detailed analysis of all of the data will be conducted to help further inform the future of the Ocrelizumab RA clinical programme.

Ocrelizumab is also being evaluated for Relapsing Remitting Multiple Sclerosis (RRMS). The treatment in the Ocrelizumab RRMS Phase II study is on-going at this time.

Source: World Pharma News

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An experimental approach that looks for the DNA leaking out from dead and dying cells may provide a route to a blood test for breast cancer, U.S. researchers reported on Tuesday.

An initial study showed the test detected 70 percent of breast cancer cases, and correctly cleared 100 percent of women who did not have breast cancer, the team at Chronix Biomedical, a privately-owned company in San Jose, California, said.

The experimental test is not ready to develop into a product but provides a basis for further research, they wrote in the journal Molecular Cancer Research.

“It is based on finding the unique DNA fingerprints from dead and dying cells,” Chronix CEO Howard Urnovitz said in a telephone interview.

Technological advances in DNA sequencing made the test possible, Urnovitz said. His team sequenced the entire genomes of 26 breast cancer patients and of 67 apparently healthy women.

They were looking for extra DNA in the blood of the breast cancer patients that would come from cells dying because of the tumors.

“If a breast cell is injured, it will overexpress the genes that make it a breast cell,” Urnovitz said. In theory, if a patient has excess DNA from breast cells that are dying, there is something going on that is killing breast cells.

The search is not easy. “The entire genome can be found in the blood,” Urnovitz said. And billions of cells die every day in the human body.

But eventually the Chronix team found what they believe is tell-tale DNA from dying breast cells.

“This study supports the potential of an entirely new approach to identifying cancer at its earliest stages when therapies may be most effective,” Dr. William Mitchell of Vanderbilt University School of Medicine in Tennessee, who worked on the study, said in a statement.

SCREENING AND MONITORING

“Laboratory tests using this approach may have the potential both to screen large populations for cancer before symptoms appear and to monitor patients for the recurrence of cancer once treated,” Mitchell added.

Much more testing needs to be done, Urnovitz said. But so far the test seems to specifically home in on breast cells. Unpublished data shows, for instance, that the DNA signature is not found in men with prostate cancer.

The cost of genetic sequencing will have to come down more before the test would be practical, Urnovitz added.

His team used Roche AG’s 454 sequencer at a cost of thousands of dollars per person, but companies are working to speed up sequencing and get the costs down.

The tests might be used to screen women for breast cancer and to tailor treatments, Urnovitz said.

“Imagine we can come in and say ‘you have damage to the protein kinase gene that would preclude you from these 10 cancer drugs, but here are 20 others that should work’,” he said.

“You would be selecting drug treatment based on each person’s lesions. This would be a really good example of personalized medicine.”

Urnovitz also hopes such a test could monitor patients who have completed treatment for cancer. Instead of coming to a cancer center to undergo a PET scan to check for tumors that may have returned, patients could get a blood test at their convenience and have it sent in for analysis.

“You could have one blood test for everything that is going on,” he said.

Source: Reuters

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In a significant setback, Biogen Idec and Roche have suspended the troubled development program of ocrelizumab for rheumatoid arthritis, and analysts are already questioning if work related to multiple sclerosis may soon follow.

The companies made their move after an independent safety board said that the risks outweighed the potential benefit from the experimental therapy, noting that serious and opportunistic infections had afflicted patients taking the therapy, some of whom died. Safety concerns had already forced researchers to halt two clinical trials for rheumatoid arthritis and lupus.

“The news wasn’t completely unexpected since some trials were on hold before,” notes Birgit Kulhoff, an analyst at Rahn & Bodmer. “However, with the obvious fatalities the drug has a high likelihood of not being approvable. I would expect that the MS trials will be stopped as well.”

“Patient safety is of the utmost importance in all of our drug development programs,” says Roche’s Chief Medical Officer Hal Barron. Kulhoff had projected blockbuster sales if the drug had gone on to an approval for all three indications.

Source: FierceBiotech

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