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By "regulatory blockage" I guess you refer to the Duch poisson pill, any idea how strong it is (previous cases) ?
Mylan planning new offer for Perrigo in the near term
http://www.cnbc.com/id/102573760
Indeed. That and the other reasons mentioned make me think the offer will not become real.
The TEVA offer for MYL looks very good to MYL shareholders and TEVA might even need to raise it.
Congrats on your MYL play.
Even in case MYL management is sufficiently desperate to up the offer for PRGO in order to save their jobs, I think MYL shareholders would prefer Teva's offer.
The "amazing" Cephalon acquisition gets better all the time
Way OT
I'm not pissed off easily (except when it's that time of the month). However, it is extremely wise of you not to put me to the test. Angry Israeli females could be highly dangerous you know
On the serious side, thank you for the kind words dewophile!
Vigodman declared they have the financial capacity to buy anything they want so that's a hint he is thinking big. I heard names like Perrigo and Meda which sound right but I wouldn't know and I am more concerned about who is going to be our next prime minister (elections day tomorrow...)
Yes, but think Mylan is too big and hard to swallow
I'm sure we'll see a long 'patent dance' with appeals process to the US PTO and up to the Federal Circuit, which could last several years...
On the "patent dance" between NVS and AMGN
Biosimilar makers flout forced patent negotiations in US
Nature Medicine : 3/9/2015
http://www.nature.com/nm/journal/v21/n2/full/nm0215100.html
By Cassandra Willyard
The first generic versions of complex drugs known as biologics are likely to gain approval in the US this year under a new, abbreviated approval pathway. But before these drugs reach the market, the companies developing these generic versions, called biosimilars, will have to settle patent disputes with the makers of brand-name biologics. The process for resolving these disputes, however, is rife with ambiguities that the courts have yet to interpret—and some lawyers assert that this could dissuade companies from producing biosimilars in the US.
Just last month, an advisory committee to the US Food and Drug Administration (FDA) recommended approval of the first biosimilar application submitted to the agency. Sandoz, the generics division of Swiss drug giant Novartis, is seeking approval for a biosimilar version of Neupogen (filgrastim), a medicine produced by the California-based biotech Amgen that helps cancer patients produce more white blood cells.
The FDA is likely to decide whether to approve the drug before summer. But even as the agency reviews the application, Amgen and Sandoz are in a legal battle over the patents pertaining to Neupogen. The drug's key patents expired in 2013, but Amgen wants assurance that Sandoz's copycat version doesn't infringe on any of its remaining patents, such as one that covers the co-administration of Neupogen and a chemotherapy drug to boost the mobilization of stem cells from bone marrow, which expires 12 December 2016. So in October 2014, Amgen filed a lawsuit against Sandoz. “This lawsuit is necessary because Defendants refuse to follow the rules,” states the complaint.
The rules in question can be found in the Biosimilars Price Competition and Innovation Act (BPCIA). The law, part of the 2010 US Patient Protection and Affordable Care Act, lays out an expedited approval pathway for biosimilars. It also includes a procedure for resolving patent disputes that contains so many carefully timed and choreographed steps it has become known as the 'patent dance.”
Under the patent dance, the applicant has 20 days from when it files its application with the FDA to hand over that same document to the company that originally developed the drug so that the latter can ensure that the generic version does not infringe on any active patents. According to Amgen's complaint, Sandoz has refused to do that. And Amgen alleges that because it doesn't have access to Sandoz's application, the company can't determine whether Sandoz is infringing on any of the patents in its extensive portfolio. Sandoz claims it offered Amgen access to its application under certain conditions, and that Amgen refused. Sandoz also argues that the BPCIA does not compel biosimilar applicants to provide their applications to the companies that make the drugs they plan to mimic.
Ditching the dance
Sandoz isn't the only biosimlar manufacturer looking to avoid the patent dance. Other companies are trying to circumvent it as well. This type of bickering is probably not what the architects of the BPCIA envisioned when they drafted the legislation. The patent dance is supposed to help resolve disputes by forcing the parties to share information and hash out their differences, says Wendy Choi, a patent attorney at Ballard Spahr LLP in Atlanta. It's intended to work like this: once the original developer of the biologic reviews the biosimilar manufacturer's FDA application, the company has 60 days to compile a list of all the active patents it believes could be infringed on by the applicant. The two parties then embark on an exchange of patent lists and explanations of infringement and validity, all according to a set schedule. The goal of this back and forth is for the two parties to reach an agreement over which patents will be the subject of the first round of patent infringement litigation.
“The fights are going to be over patents where the biosimilar says, 'I don't think I actually practice this patent. Under your interpretation I infringed it, but I don't really think I do what you're claiming,'” says Hans Sauer, deputy general counsel for intellectual property at the Biotechnology Industry Organization (BIO), a trade association representing biotechnology companies. Whether or not one company has infringed on another's patent is rarely straightforward. “A patent is a very long and complex document,” says Erika Lietzan, a law professor at the University of Missouri School of Law in Columbia. “For infringement, you have to interpret every single term in the claims and then you have to determine whether the biosimilar is doing that exact thing.” The dispute might come down to a slight difference in pH.
Daniel Scolnick, a patent attorney with Pepper Hamilton LLP in Berwyn, Pennsylvania, sees what those who drafted the act were trying to accomplish. “They're trying to get the parties to come to an agreement, to narrow the issues,” he says. “I think they tried to make it simpler.” But at this point, he adds, “no one really understands how it's going to work.” And, so far, Sandoz and other biosimilar manufacturers haven't seemed willing to participate in the BPCIA's patent dispute resolution process.
Terry Mahn, a patent attorney at Fish & Richardson in Washington, DC, isn't surprised to see biosimilar makers trying to sidestep the patent dance. “They don't want to have to disclose their application and the information on their manufacturing process,” he says. “You're giving the enemy all the secrets to your business.”
Some aspects of this forced negotiation might also be unappealing to developers of brand-name biologics. For example, if the two parties can't agree on which patents are involved, the biosimilar maker can limit the number of patents contested in the first round of litigation to as few as one. “I think both sides are reluctant participants in this dance,” says Kenneth Zwicker, an expert in patent-infringement litigation at the Boston law firm Lathrop & Gage.
Advance move
Sandoz's alleged refusal to hand over its filgrastim application isn't the company's first attempt to bypass the patent dance. In 2013 the company filed a lawsuit against Amgen and Hoffman-LaRoche over another drug, a generic version of Amgen's Enbrel (etanercept). Although Sandoz hadn't yet filed an application with the FDA and was still testing its version of etanercept in a phase 3 trial, the company asked the California Northern District Court to issue a declaratory judgment that its biosimilar will not infringe on two of Amgen's patents, and that those patents were invalid and unenforceable, in part, because they had been issued more than a decade and a half after they were first filed.
In November 2013, the judge dismissed the case as premature as Sandoz had not yet engaged in the BPCIA's patent information exchange process. The decision also stated that Amgen's patents posed no immediate threat because Sandoz had not yet filed an application with the FDA. Sandoz appealed the decision, but on 5 December 2014, a Federal Circuit court upheld the ruling. Notably, however, the federal judge declined to rule on whether biosimilar manufacturers must participate in the patent dance before heading to court. The decision “is unfortunate in a way,” Choi says, “because all the parties involved want clarity.”
At least three similar complaints have been filed by drug companies hoping to challenge the patents that cover Remicade (infliximab), Janssen's blockbuster anti-inflammatory medicine. In March 2014, South Korean biosimilar maker Celltrion, which has developed its own version of infliximab, launched two separate lawsuits, one against Janssen over three Remicade patents it believes to be invalid, and another against Kennedy Trust for Rheumatology Research, which granted Janssen a license for patents covering the co-administration of Remicade with another arthritis drug. And in August 2014, the Illinois-based pharmaceutical and medical device company Hospira, which has an agreement with Celltrion to co-market their Remicade copycat, filed a lawsuit against Janssen over some of the same patents. Celltrion eventually dropped the case against Janssen, and the other two cases were dismissed by the district court in December 2014. “Celltrion's attempts to skirt the BPCIA's dispute resolution mechanisms while reaping the benefits of its approval process is improper,” the court noted. However, none of these cases have reached federal court.
Amgen is hoping that its suit against Sandoz will conclusively settle the issue. On 6 January, the day before Sandoz received the green light from the FDA's advisory committee, Amgen filed a motion urging the court to rule that Sandoz's failure to provide its biosimilar application to Amgen violates the BPCIA and constitutes unfair business practices under California law. But a decision in this case could easily be a year to 18 months away, Scolnick says. “It will probably take a significant amount of time to figure the scope of the law and how it will be applied.”
What all this uncertainty means for biosimilar development in the US is not yet clear. Choi, who often lectures in Asia, says that many biosimilar companies there are interested in bringing their drugs to the the US, but they're deterred by the BPCIA's patent dance. “If they were thinking about sticking their toe in the water, this made them back up and say, 'Ok, we're going to wait a little bit,'” she says. However, if the courts rule that biosimilar companies can avoid the patent dance and instead resolve patent disputes through some simpler process, “that could have the effect of enticing others to develop more biosimilars,” says Kurt Karst, an attorney at Hyman, Phelps & McNamara in Washington, DC.
But Lietzan isn't convinced the patent dance or the uncertainties surrounding its enforcement are acting as a deterrent. “There is a lot of money at stake,” she says. Decision Resources Group, a healthcare analytics firm, estimates that by 2022 the US biosimilars market will reach $11 billion. “The notion that anybody is holding back on getting an approvable product to the FDA simply because they're concerned that these court cases are going to come out in favor of having to do the patent dance is ludicrous,” Lietzan adds.
For companies willing to take the plunge, Zwicker worries that the patent dance could drive up the cost of biosimilars. “You're generating a lot of legal work, by both the parties, including the biosimilar,” he says. “And they're going to have to recoup those expenses.”
I don't recall NVS gave the actual sales figures of individual products but it stated few time about the success of Zarzio in Europe. For example:
"Sandoz G-CSF biosimilar, Zarzio, continued to strengthen its leading position as the number one filgrastim product in Europe by volume, ahead of Amgen’s Neupogen® and Chugai’s Granocyte®."
http://www.novartis.com/downloads/newsroom/corporate-fact-sheet/4a_Sandoz_EN.pdf
Or this one:
"ZARZIO is the number one biosimilar filgrastim globally and is the leading daily G-CSF in Europe with 30 percent volume market share."
http://www.novartis.com/newsroom/media-releases/en/2014/1835571.shtml
Re: Zarxio sales forecast in the US
Neupogen FoBs are great success in Europe and Zarzio is in the lead. In the US, Teva's version of Neupogen entered the market over a year ago but it isn't a real competitor as you know. Zarxio will do a lot better when it will enter, say 30% market share. Of course, if NVS can get pharmacy-level interchangeability sales will shot up. What will it take and how long before this happens?
Re: safety halt for B-I’s BACE drug due to skin reactions
My first thought was this ß-secretase inhibitor might cause an adverse effect similar to that of the late ?-secretase - semagacestat.
Re: 23andMe
Although I do believe that people have the right to get their personal genetic information, I also think they need to be protected from it. So I think Gutierrez has a valid argument.
Once FDA was pressured by top scientists (Landers, Collins, Varmus and like), it had no way to stop the flood. 23andme is just one beneficiary:
In NEJM, Lander Lauds Steps at FDA to Build New Regulatory Framework for Genomic Tests
https://www.genomeweb.com/regulatory-news/nejm-lander-lauds-steps-fda-build-new-regulatory-framework-genomic-tests
Feb 18, 2015/a GenomeWeb staff reporter
NEW YORK (GenomeWeb) – What makes next-generation sequencing-based diagnostic tests alluring also makes them complicated to regulate, but changes to the regulatory framework could ease the adoption of such tests, the Broad Institute's Eric Lander wrote in a Perspective article in the New England Journal of Medicine this week.
Lander said that it would take time to build the necessary regulatory framework at the US Food and Drug Administration to deal with NGS-based tests, but he noted that the agency had "already taken small, but significant steps" when it approved Illumina's MiSeqDx sequencing platform, two associated assays, and a library prep kit in 2013.
Lander, who is also the co-chair of the President's Council of Advisors on Science and Technology, called the issue the FDA faces in regulating NGS-based diagnostics a "knotty" one.
NGS-based tests can uncover variants throughout the genome, even ones in genes clinicians don't necessarily know to watch for. But gene tests and other in vitro diagnostics are currently evaluated by how accurately and reliably they identify the gene, protein, or other substance of interest, and whether the results from the test correctly identify the related disease or condition.
As Lander pointed out, a narrow interpretation of the FDA regulatory framework would mean that for each NGS-based test, each of the three billion nucleotides of the genome would need separate analytic studies, and each company presenting a test covering the same gene or variant would have to provide their own data supporting the link between that variant and disease.
Others, like Francis Collins, the director of the US National Institutes of Health, and Harold Varmus, the director of the National Cancer Institute, in their own recent NEJM article have also highlighted the need for changes to the regulatory framework to enable the use of new tests and the adoption of personalized medicine.
The FDA, Lander noted, has begun to investigate new regulatory approaches.
"As I've engaged in planning for the [Precision Medicine Initiative] over the past year ... I've been thrilled to see that the FDA — sometimes viewed as hidebound — has been exploring radical new approaches for cutting the Gordian helix in which genomic testing has been bound," he said.
In its recent approval of Illumina's MiSeqDx sequencing platform and related assays, the agency took a slightly different regulatory tack — one it noted in a discussion paper posted at its website — that could be implemented for other NGS-based tests.
"FDA is considering new regulatory approaches only for NGS tests because this technology allows broad and indication-blind testing and is capable of generating vast amounts of data, both of which present issues that traditional regulatory approaches are not well-suited to address," the agency said.
The MiSeqDx system, for instance, was able to demonstrate its analytic performance using a representative subset of variant types that appear in different sequence contexts. For the associated cystic fibrosis assays, Illumina was able to provide evidence for the clinical relevance of certain variants by drawing on a community-created and -curated database of cystic fibrosis mutations.
Going forward, Lander argued that software programs could be developed to validate new sequencing platforms and that community-curated databases like the NIH-funded Clinical Genome Resource project could, if scaled-up, provide the needed data about the links tying genes, variants, and diseases together.
He further envisioned a situation in which FDA could provide a "safe harbor" so that developers whose genomic tests have interpretations consistent with such databases wouldn't have to provide additional validation, though they could seek approval for tests based on other interpretations.
But, Lander noted, "Fleshing out these ideas will require a lot of work."
In its preliminary discussion paper, FDA asked the community for feedback, and the agency is to hold a public workshop this week to discuss these potential new regulatory approaches for next-generation sequencing-based tests.
Re: NVS’ Neupogen FoB
Nature news (free access) report on biosimilars:
http://www.nature.com/news/first-biosimilar-drug-set-to-enter-us-market-1.16709
>>BIIB anti-LINGO drug
BIIB anti-LINGO drug
Thanks, Ian and Roy for your comments.
ACT/AGN
Think VRX will try to outbid?
MDVN/CureTech's anti-PD1 pidilizumab (CT-011)
Back when Teva was in charge, they have focused on hematologic malignancies and also tested the compound in several solid tumors (advanced prostate cancer was one), but don't think any type of breast cancer was one of them.
MDVN just licensed CureTech's anti-PD1 pidilizumab (CT-011), that TEVA had dumped, for peanuts:
http://finance.yahoo.com/news/medivation-inc-licenses-clinical-stage-211200638.html
AD company
They shown reversing and repairing damages caused by neurodegenerative disease/injury in several animal models and hope to see this in humans.
Well, they could at least go for mild to moderate, not the moderate to sever AD patients, as the latter are too far progressed to gain from any treatment.
I have recently talked to an Israeli company that started a clinical trial in moderate to severe Alzheimer's a while ago. One of the big question marks i had was - why they've chosen to enroll very advanced patients not those with an earlier stage of the disease.
I think MRK keeps its expectations for MK-8931 low.
BACE-for-AD
LLY and Roche terminated their BACE inhibitor programs a while ago due to toxicity. Merck is in phase III and a couple of others are behind.
[OT] (TEVA/MNTA)—Chutzpah defined
It qualifies as chutzpah, but the best definition of Chutzpah I've heard is when somebody kills both his parents and begs the court for mercy because he’s an orphan :)
HPTX
It was indeed a sloppy due diligence but someone at Andromeda conducted a substandard test and messed up with the design and analysis. On top, some manipulated the numbers. Others (at CBI?) knew. It is criminal and I would like to know the names of those who cheated.