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On your first question my opinion is still the same ie I don't think Teva's generic is Lupenox. On your other question, I'd like to see Bill Marth exercises "the right to remain silent" more often.
That's their Letter to the Editor:
http://www.scielo.br/pdf/abc/v95n4/en_22.pdf
Good call on Letairis in IPH:
Gilead Terminates Phase III Clinical Trial of Ambrisentan in Patients with Idiopathic Pulmonary Fibrosis
http://finance.yahoo.com/news/Gilead-Terminates-Phase-III-bw-3130798699.html?x=0
ARNA - from this morning’s press release
GILD to acquire Arresto Biosciences, a privately-held company for $225M, gaining experimental medicines for cancer and a fatal lung disease.
http://www.gilead.com/pr_1509319
I don't know about Deciphera but if rkrw doesn't know much it tells me no further digging is needed.
I don't think it's funny unless you find giving the legal department more work to be funny. Seriously, I think Teva knows this CP will be rejected. The purpose seems to be discussing the five criteria from generic Lovenox approval with regard to Copaxone and also asking for an advisory committee.
Any sense on this agent from Deciphera? I see that Dr. Moshe Talpaz is one of the principal Investigators.
http://clinicaltrials.gov/ct2/show/NCT00827138
I was wondering what "Rater-blinded Design" means...
I guess safety counts for something...
BRAVO study started in 2008 and compares Laquinimod vs Avonex and placebo.
http://clinicaltrials.gov/ct2/show/NCT00605215
Teva Announces Successful Results of Phase III Study with Oral Laquinimod for Multiple Sclerosis
http://www.tevapharm.com/pr/2010/pr_976.asp
Jerusalem, Israel, December 9, 2010 - Teva Pharmaceutical Industries Ltd. (NASDAQ: TEVA) and Active Biotech (NASDAQ OMX NORDIC: ACTI) announced today initial results from the two-year Phase III ALLEGRO study, which demonstrated that relapsing-remitting multiple sclerosis (MS) patients treated with 0.6 mg daily oral laquinimod experienced a statistically significant reduction in annualized relapse rate compared to placebo. Additional clinical endpoints, including significant reduction in disability progression,
as measured by Expanded Disability Severity Scale (EDSS), were also achieved.
Laquinimod was safe and well-tolerated. The overall frequencies of adverse events were comparable to those observed in the placebo group.
No deaths were reported in laquinimod-treated patients. Overall incidence of infections was similar between the two arms of the trial.
"This pivotal study met its primary endpoint while maintaining a very good safety profile," says Principal Investigator, Professor Giancarlo Comi, Director of the Department of Neurology and Institute of Experimental Neurology at the University Vite Salute, San Raffaele, Italy.
"Laquinimod demonstrated a significant reduction in the progression of disability which may be explained by its unique mechanism of action that includes neuroprotective properties. Laquinimod may therefore be a promising therapeutic option for the MS community."
"We are very pleased to have achieved this major milestone in the development of oral laquinimod, a novel therapy that can potentially improve the lives of many MS patients in a safe way," said Shlomo Yanai, Teva's President and Chief Executive Officer.
Additional analyses of the ALLEGRO study data are ongoing, and detailed results will be submitted for presentation at a leading scientific conference during the first half of 2011.
Laquinimod received Fast Track designation from the U.S. Food and Drug Administration (FDA) in February 2009. The second phase III study, BRAVO is still ongoing with results anticipated in the third quarter of 2011.
Regulatory submissions in the U.S. and the EU will then follow.
In addition to the ongoing MS clinical studies, laquinimod is currently in Phase II development for Crohn’s disease and Lupus, and is being studied in other autoimmune diseases.
Following the successful study results, Teva filed a patent application covering the use of laquinimod in slowing the progression of disability in MS patients.
ABOUT LAQUINIMOD
Laquinimod is a novel once-daily, oral immunomodulatory compound being developed as a disease-modifying treatment for MS. The global Phase III clinical development program evaluating oral laquinimod in MS consists of two pivotal studies, ALLEGRO and BRAVO.
- The first clinical study, ALLEGRO, was a two-year multi-national, multi-center randomized, double blind, placebo-controlled study designed to evaluate the efficacy, safety and tolerability of laquinimod in MS patients. The study was conducted at 139 sites in 24 countries and enrolled 1,106 MS patients. Patients were randomized to receive a once-daily oral dose of 0.6 mg laquinimod or matching placebo. The primary outcome measure was the number of confirmed relapses; secondary measures included confirmed disability progression and changes in MRI active lesions,. Patients who completed the ALLEGRO study are offered to join an open-label extension phase, in which they will be treated with laquinimod 0.6mg daily until the drug is commercially available.
- The second clinical study, BRAVO, is a two-year, multi-national, multi-center, randomized, double-blind, parallel-group, placebo-controlled study designed to compare the safety, efficacy and tolerability of a once-daily oral dose of 0.6 mg laquinimod over placebo and to perform a comparative risk-benefit assessment between laquinimod and interferon beta-1a. Enrollment of 1,332 patients at 154 sites in the U.S, Europe, Israel and South Africa was completed in June 2009. BRAVO study results are expected in the third quarter of 2011.
In addition to the ongoing MS clinical studies, laquinimod is currently in Phase II development for Crohn’s disease and Lupus, and is being studied in other autoimmune diseases.
ABOUT MULTIPLE SCLEROSIS...snip
Well, I haven't seen too many in Globes or Themarker plus their translations are horrible.
Just curious, have you seen many analysts bother correcting these kind of misstatements?
I doubt Ronny Gal said that.
Resveratrol (SRT501): Development Halted
http://pipeline.corante.com/archives/2010/12/01/resveratrol_srt501_development_halted.php
Posted by Derek
Back in May, GlaxoSmithKline halted a trial of SRT501, which is a formulation of resveratrol, in myeloma. Now the folks at the Myeloma Beacon site are the first with the news that the company has halted all further development:
According to a GlaxoSmithKline spokesperson, an internal analysis of the kidney failure cases has concluded that they “most likely were due to the underlying disease … However, the formulation of SRT501 was not well tolerated, and side effects of nausea / vomiting / diarrhea may have indirectly led to dehydration, which exacerbated the development of the acute [kidney] failure.”
For this reason, the company decided to halt further development of SRT501 in multiple myeloma. The SRT501 formulation of resveratrol “may only offer minimal efficacy,” explained the Glaxo spokesperson, while increasing the chances of kidney failure. . .
. . .In a separate statement to The Myeloma Beacon, a Glaxo spokesperson explained the rationale for the company’s decision to halt all development of SRT501. Ending all work on SRT501, the spokesperson said, will allow Glaxo to focus its resources on the development of drugs that act similarly to SRT501, but have more favorable properties. The spokesperson mentioned, in particular, SRT2104 and SRT2379 as drugs similar to SRT501 that the company is developing.
These compounds are still a bit of a mystery - they've been in the clinical trial registry for a while, and are certainly the subject of active investigation, but we don't know how they fit into the whole activation-of-SIRT1 brouhaha. They haven't been challenged by the critics of the work, nor specifically defended by GSK, so we're just going to have to see how they perform out there in the real world (which was always going to be the final word, anyway).
But this would appear to be it for resveratrol itself in the real world, as far as GSK's concerned. Hey, does this mean that they'll let their two former Sirtris execs start selling it again on the side, now that they have no interest in the parent compound? One doubts it. But why not?
Fascinating! especially the observation that tissue degeneration and organ function can be restored.
P.S. The paper I've posted about here http://siliconinvestor.advfn.com/readmsg.aspx?msgid=26344474 on restoring telomere elongation in cells taken from dyskeratosis congenita patients (they carry mutations that cause telomerase to be defective), is a good accompanying read. Now, if only reprogramming or reactivating telomerase in humans can be done safely...
PLX latest presentation here took place some 10 days ago and there weren't any big news. Waiting for the 2/25/11 PDUFA date. Approval in Israel is expected about 2 months later and in EU by end of 2011. Treating dozens of patients in France and about the same no. in Brazil. Talked about the bone issue and that this is going to be further investigated via a post marketing trial.
The roots of resistance
http://www.nature.com/news/2010/101124/full/468490a.html
Learning how melanoma fights back may yield new therapies.
Heidi Ledford
A promising new cancer drug called PLX4032 made waves earlier this year for its success against the deadly cancer melanoma. The results of a clinical trial were dramatic, with some patients emerging nearly cancer-free. But for most, the drug stopped working about seven months after therapy began, and the tumours returned1. This week, two follow-up studies reveal why PLX4032 fails and how tumours' resistance to it might be overcome.
About half of patients with melanoma have a mutated version of the B-RAF protein, which is thought to help trigger the growth of tumour cells. PLX4032 was designed by Plexxikon, a pharmaceutical company in Berkeley, California, to selectively inhibit it. In one study2, PLX4032 shrank tumours in 24 of 32 patients with B-RAF mutations. But tumours often evolve ways to evade treatment, and this was no exception. Levi Garraway, an oncologist at the Dana-Farber Cancer Institute in Boston, Massachusetts, and his colleagues have now found that excessive production of a cancer-promoting protein called COT can shield cultured cells from PLX4032. High levels of COT were also found in two of three PLX4032-resistant tumours taken from patients who had received the drug3.
A group led by Roger Lo, a dermatologist at the University of California, Los Angeles, found two other ways for tumour cells to short-circuit PLX4032: by reactivating the B-RAF signalling pathway damped down by the drug, or by stimulating tumour-cell growth mediated by a different protein4. Larger studies will be needed to assess the importance of both groups' results for clinical applications.
Still, the findings are a crucial step towards determining how to overcome PLX4032 resistance, says Alexis Borisy, chief executive of Foundation Medicine in Cambridge, Massachusetts, which is developing diagnostic tests for tumours. Pharmaceutical firms have already started clinical trials to test PLX4032 in combination with experimental drugs that inhibit MEK, a protein involved in cell growth. When Garraway's team tested this combination in their cultured tumour cells, they found that it overcame the effects of high levels of COT expression.
Clinicians may need to combine four or more drugs to create a potent cancer-fighting cocktail, says Borisy. PLX4032 is a good place to start, he notes: its highly selective targeting of B-RAF means it could have fewer unwanted side effects. "It's an exciting opportunity," he says.
* References
1. Ledford, H. Nature 467, 140-141 (2010). | Article | PubMed | OpenURL
2. Flaherty, K. T. et al. N. Engl. J. Med. 363, 809-819 (2010). | Article | PubMed | OpenURL | | ChemPort |
3. Johannessen, C. M. et al. Nature advance online publication doi:10.1038/nature09627 (2010).
4. Nazarian, R. et al. Nature advance online publication doi:10.1038/nature09626 (2010).
No one thinks MNTA needs to prove MoA. The MoA was mentioned because the lack of knowledge about it is a hurdle and so is the lack of in vitro/in vivo assays (in opposed to Lovenox).
Ps hoa to you too.
I don't think Copaxone is easier to replicate not only chemically but also to show equivalence. However, I do believe Momenta has the technology. Problem will be to convince the FDA they have good enough data and/or the right assays.
Drug giants turn their backs on RNA interference
http://www.nature.com/news/2010/101123/full/468487a.html?s=news_rss
A once much-touted technique faces a difficult transition to the clinic.
Heidi Ledford
Not long ago, a technique called RNA interference (RNAi) seemed to be on the fast track to commercial success. Its discovery in 1998 revealed a new way to halt the production of specific proteins using specially designed RNA molecules, and it quickly became a favourite tool of basic research. In 2006, the scientists who made the discovery were awarded the Nobel prize for medicine, and the New Jersey-based pharmaceutical giant Merck paid more than US$1 billion to snatch up Sirna Therapeutics in San Francisco, California — one of the first biotechnology companies aiming to harness RNAi to create new drugs.
Yet all that seemed like ancient history last week when drugs and diagnostics corporation Roche in Basel, Switzerland — a major investor in RNAi-based drug research — announced it was killing its programme after spending three years and more than $500 million on the technique. Although part of a larger restructuring to cut costs, the move is the latest indication that big pharma may be losing faith in RNAi.
"The momentum now seems to be heading a bit against RNAi," says Alan Carr, an analyst at Needham & Company, an investment-banking firm in New York. Roche's 17 November announcement, which sent stock prices at RNAi companies plunging, came just two months after another Swiss-based multinational, Novartis, declined to spend $100 million to extend a partnership with Alnylam, a prominent RNAi company based in Cambridge, Massachusetts.
The development of RNAi-based drugs has stalled as companies confront the challenge of delivering RNA molecules, which are notoriously fragile, to target cells in the human body, and then coaxing those cells to take up the RNA. "Getting these molecules exactly where we want them to go is a little more difficult than originally thought," says Michael French, chief executive of Marina Biotech, an RNAi company based in Bothell, Washington.
Of the dozen RNAi-based therapeutics in early clinical testing, most apply the RNA molecules directly to the target tissues, or aim to shut down the production of a protein in the liver, which takes up the RNA as it filters the blood (see Table 1). Several candidates also package the RNA within a lipid nanoparticle, a delivery vehicle that both protects the RNA and allows it to be shuttled across cell membranes. Investors expect Alnylam to emerge in the next few years with the first commercially viable RNAi-based therapeutic, which would treat a rare disease called transthyretin amyloidosis — in which an abnormal form of a blood protein is deposited in the nerves and organs — by shutting down the production of the protein in the liver.
Although Alnylam shed about 50 of its 225 employees when its partnership with Novartis ended, chief executive John Maraganore is optimistic. "There's going to be a steady drumbeat of increasing frequency that really validates RNAi as a whole new drug class," he says. "We're feeling pretty damn good about where things are right now."
Until that validation arrives, investors may be wary of the RNAi platform, says Josh Schimmer, an analyst at the investment bank Leerink Swann & Company in New York. "Alnylam has a very interesting drug at this point," says Schimmer. "It's premature to say they have a very promising platform."
Companies such as Alnylam have built their business by enticing big pharmaceutical companies in as partners. That strategy has paid off: Alnylam has $372 million in cash, an unheard-of sum for a young biotechnology company with no drugs yet on the market. But the number of deals with major pharmaceutical firms has slowed, says Carr. "There was a wave of interest earlier on and it's just not there now."
Some holdouts remain. Merck spokeswoman Carolyn Lappetito says her company has not pulled back from RNAi. "It's a long haul," she says. "We have not decided to make any big changes." And although Novartis ended its relationship with Alnylam, the company can now develop the 31 RNAi-based candidate drugs generated during the five-year partnership. In comparison, the three years Roche spent in the field hardly seems enough time to fully evaluate the technique, says Maraganore. "Three years is nothing," he adds. "It's like kicking your three-year-old out of the house and telling him to get a job."
On Roch' Q3 2010 call, Pascal Soriot commented on the NEI trial:
I thought physicians aren't allowed to self promote themselves nor the procedures they perform. However, I guess that asking these women to abstain from junk food and change their life style is worthless.
Next year, data from the National Eye Institute Lucentis-Avastin Trial ( http://clinicaltrials.gov/ct2/show/NCT00593450 ), should increase Avastin's 65% share of US procedures for wet AMD.
The other endothelin receptor antagonist - Letairis, also goes off patent in 2015.
Feds OK [lifts hold on trial] 2nd human study of embryonic stem cells
http://www.google.com/hostednews/ap/article/ALeqM5iV-y2_ENCAejeB0cF2WB9ZaWKjoQ?docId=efc04bbc3e3f4ef8b22be9ef7b6124d8
NEW YORK (AP) — For only the second time, the U.S. government has approved a test in people of a treatment using embryonic stem cells — this time for a rare disease that causes serious vision loss.
Advanced Cell Technology, a biotechnology company based in Santa Monica., Calif., said the research should begin early next year, following the green light from the U.S. Food and Drug Administration.
Just last month another biotech company, Geron Corp., said it had begun preliminary testing in people for treating spinal cord injuries by injecting cells derived from embryonic stem cells.
Scientists hope to use stem cells to create a variety of tissues for transplant. But human embryos have to be destroyed to harvest those cells, which has made their use controversial.
ACT's experiment will focus on Stargardt disease, which affects only about 30,000 Americans. But the company hopes the same approach will work for similar and more common eye disorders like age-related macular degeneration, which affects millions.
Stargardt is an inherited disorder that attacks central vision used for tasks like reading and recognizing faces. Some patients go totally blind, even losing peripheral vision, while others are severely impaired and can only perceive light or see their hands moving in front of their faces.
The disease typically starts in adolescence. The key problem is that impaired scavenger cells fail to remove toxic byproducts from the eye, allowing them to build up and kill other cells. There is no proven treatment.
In the new study, 12 patients will be treated with healthy scavenger cells, created in a laboratory from human embryonic stem cells. This early phase of the research is primarily to test the safety of various doses, injecting only one eye of each patient.
"We're also hoping to see some improvement in visual acuity, but that's a bonus," said Dr. Robert Lanza, ACT's chief scientific officer.
The research will be performed at medical centers in Massachusetts, New Jersey and Oregon, ACT said.
Stephen Rose, chief research officer of the Foundation Fighting Blindness, said his group is "very, very glad" that ACT has permission to begin the study.