Sunday, October 23, 2016

[U] "Salmon, Rising" -- Sarepta's Exondys 51® [Eteplirsen]: For Duchenne MD

While we wait patiently for The mighty battleship rises(!), takes the fly and line, running free now -- on this crisp cool clear fall Sunday morning. I'll post the graphic I just finished -- which gives a sense of the scale of this molecular entity. [Recent backgrounder of mine, here.]

That is one honkin' big structure. Okay Salmon -- the graphics are loaded; the FDA's new meds science guy has weighed in on your side -- and so now we await post your take (Parts I and II).

. . . .Salmon rising:

First a correction. As you noted the press is claiming the advisory committee voted 7-6 against approval. Actually the vote was 7-3 with 3 abstentions. Abstentions are often the made when people want to vote no but are afraid of the political fallout to their careers such as denial of future grants. So the advisory committee vote was clearly lopsided against approval.

The documents the FDA has released about this are also fascinating with regards to the internal politics.

Although the press has made it out as this was Ron Farkas, the team leader, who was holding up the approval this is not the case. First the team leader takes his cue from the primary reviewer.

Then not only was the primary reviewer and the team leader against approval, but so was the Neurology Division Director who writes the recommendation. It then goes to the Office Director, Ellis Unger, who makes the final decision and he was also against approval. Above the Office Director is the Director of the Office of New Drugs, John Jenkins, who was also against approval. It was at this point that Janet Woodcock was clearly pushing for approval as indicated by her statement at the advisory committee meeting.

Ellis Unger then took this to the Scientific Review Board. The Scientific Review Board then sided with Dr. Unger and said it shouldn't be approved. As Dr. Woodcock was then going to abuse her authority and issue an approval anyway Dr. Unger then made an appeal to FDA Commissioner Califf who basically said you had your opportunity to be heard through channels but I'm leaving the decision up to Woodcock. (Since the FD&C Act actually gives the approval decision to the Secretary of HHS it's delegated down. So Califf, by giving the decision to Woodcock, in fact made the actual decision.)

There have also been op-ed articles in the press and blogs on the internet that are clearly misleading. One such post from a former FDA official who is now an industry consultant claimed that the AC vote was rigged because the AC members were asked whether the study was adequate and well controlled. Yet this is the legal standard in the Food Drug and Cosmetics Act which requires it be determined by experts in the field. Thus he criticizes the FDA for simply asking the AC members if the drug met the legal standard for approval which the AC members (who are experts in Neurology who the law specifically says must make such a determination) essentially said it didn't. Whereas (in actuality) the decision was made by a single non-expert Janet Woodcock.

In another post an industry front group claimed that an FDA insider told them that this was just people inside the FDA who were overly concerned about safety. Yet there were essentially no complaints about safety by anyone opposed to approval and it was all about that the drug simply hasn't been shown to work. I've noticed that this is a meme that has been recently been put forth by industry in a lot of complaints about the FDA in attempts to decrease approval standards. While I don't know who the FDA insider is we need to consider that it has to be someone who has knowledge of the review and has the connections to actually speak to this (small) industry front group and get their position out and who has a particular ax to grind. In my [Salmon's] opinion the most likely candidate for this FDA insider (as someone who actually has knowledge of the situation) is Janet Woodcock. Clearly not someone who is impartial and who is someone who likely to leave the agency soon and move on to be on boards of directors.

As for costs: It's being claimed that the costs will be $300,000 per year. However this will be after rebates of 50%. Now I don't know what private insurer will allow payments for something that clearly all the experts have said hasn't been shown to work. Thus it's likely that the costs will fall on Medicaid and since Medicaid can't negotiate prices I don't know what rebates will actually be offered. Secondly this $300,000 (actually $600,000 per year) is based on a dosages for a kid weighing 25 kg (i.e. and 8 year old) with doses going up based on weight. Now an average adult male is 75 kg and assuming a linear dose relationship we could be talking closer to $2 million per year per adult patient. Plus have you seen the photos of some of the kids who testified and can barely walk around. They're morbidly obese. So with a 1000 kids nationwide we could easily be talking a $1 Billion per year. Plus if the bill before the senate passes (which Obama has promised to sign) other indications can be approved based on anecdotal claims. So for the other 90% of people with other forms of Muscular Dystrophy we could be talking $10-$20 billion per year for a placebo. (Now the finances are not my forte so if rebates are bigger than I expect, it might not be this high.)

As for parents and anecdotal data: One mother who testified at the AC meeting has a blog and is claiming Exondys will allow her kid to function and hold a job and not be a financial drain on society. How? Even if it works as claimed were' talking about slowing down a progressive decline and the kids will still barely be able to walk. Do we really believe that they won't be so physically overwhelmed that they will be able to run around and hold a job and be independent. I don't think so. In truth I think it would be cheaper to simply pay for round the clock care for these kids than to waste money on something that as of right now we don't have any good evidence that it's anything other than a placebo.

As for the claims that it's safe: It's only been tested in 12 kids! Since it takes at least 3 times as many people as the incidence that something occurs at to make sure you see at least one case of something, this means the only thing we can say is that the rates of various serious adverse reactions such as death likely occur in less than 1 in 4 people.

It this the kind of decision-making we want? "Well there's no evidence it works -- but it turns out to kill 1 out of every 5 kids who take it. . . .?" I'm not saying this will be the case for this drug, but that's the standard we're putting in place and it (or something similar) will occur eventually.

While my comments may seem harsh as to the families -- I truly do want the best for their kids. But when you approve things that have not been shown to work but you believe it might no one is going to sign up for studies the confirmatory trials or for new drugs from a different company that might actually work and truly help their kids. So if they or others have kids in the future with this horrible disease they may very well be condemning them to not having any effective treatments when there might have been if they hadn't insisted on an approval for a drug such as this before it had been shown that it actually works. . . .

There you have it. We will keep an eye on the law of small numbers effect, here -- to see whether it dissipates, or worsens -- in the ongoing larger clinical post-marketing studies. But I agree -- up and down the line -- with Dr. Salmon. Thank you once again, man.

And now, in truth, I Can't. Stop. Smiling. My. Cubs. Are. Series-bound. [Sadly, I was in a box-seat, in the friendly confines, on the night of October 14, 2003 -- the unlucky thirteen years ago, when they were just five outs away from the Series -- and well. . . Bartman happened, to Moises Alou. The Marlins went on to win the NLCS series. And we waited. And waited.] But now, we have returned the doorstep of history, once more. . . smile. Onward, to Cleveland -- Tuesday evening.


Saturday, October 22, 2016

Last Appearance: 1945; Last World Series Championship: 1908

So it's been since 1908:

Back when women
weren't yet enfranchised,
Henry Ford had just
introduced the Model T,
and the Wright brothers
had only recently
flown at Kitty Hawk. . .
ball clubs traveled
almost solely by
overnight trains. . . .
The very first Gideon
Bible was placed
in a hotel room that summer.
William Howard Taft beat
William Jennings Bryan (an
earlier Trump-style
candidate); he was
elected our 27th President.

Cleveland -- the pending opponent -- last
won it in 1948; we last appeared in it
three years before that.

And. . . my grandfather was nine years old (World War I was still a long way off) when the Cubs last took a World Series pennant home -- for the hog-butcher to the world. His father's father had owned a tavern in Chicago, back then (and may have followed those Cubs, in his retirement, by newspaper reports) -- but my grandad's dad had moved to the Rockies, and become a miner, by the time my grandfather was born. . . .

I am silent. Dumbfounded -- without words. Four wins to go. Joe Tinker (above) is grinnin'. Whoosh -- g'night. . . .


Condor's Conjecture Dept.: Did Shkreli Try (Impotently) To Influence KaloBios Chapter 11 Exit Valuations -- In The Spring of 2016?

At the head -- this is simply a Condor conjecture. Overnight, Mr. Shkreli announced via tweet that he is going to sue a company called AudioEye. Yawn.

It seems to be a perfectly fine company. But one of its current members of the smallish board of directors founded Batuta Advisors, a controlled/controlling affiliate of the entity that gave the independent financial advice and oversaw the valuation work -- (wait for it!) in the KaloBios Chapter 11 consensual workout.

Again, I am sure that director is an entirely ethical man. But I am equally sure Mr. Shkreli is. . . the opposite of all that. Just my opinion.

So in some more non-Merck-ified fare. . . I wrote this last night elsewhere.

Since we are offering pure trivialities on this Friday evening, let me close with an ironic one: Mr. Shkreli claims he lost over $1 million that he says he invested in something called AudioEye, and so he is (wait for it!) filing a securities class action suit. Uh-huh. And "the class" is... one person -- more of gnome if the truth be known, and less a fully formed human.

Martin Shkreli: "...I invested $1,050,000 in Audioeye and lost nearly all of it. I'm moving forward with a class action. RIP Audioeye..."

You see Mr. Shkreli, there have to be others similarly situated, for it to be even considered as a class action. But you go right on ahead, Perry Mason, Jr.!

It is fascinating, though that the founder of Batuta Advisors (remember that name from KaloBios' bankruptcy!?) is/was on the board of AudioEye. Click image at right to embiggefy, again.

Small world. Small world, indeed.

I am sure -- without doing any real diligence -- that AudioEye is a perfectly fine company. To elaborate on my guesses here, though, I could easily imagine that Mr. Shkreli THOUGHT (incorrectly, of course) that by putting $1 million into AudioEye, he'd be able to subtly influence the valuations -- and thus his ultimate payout -- in the KaloBios Chapter 11 exit.

He was incorrect simply because most business people endeavor to be honest.

In topsy-turvy Shkreli world, then -- being honest and doing one's job on a board or as an advisor is. . . a fraud -- at least as to Mr. Shkreli's (allegedly) dishonest schemes. So now he's suing AudioEye, in retribution. That's the Condor guess.

Yep -- That's my thought. Now you know. And. . . Go Cubs Go!


Friday, October 21, 2016

Non-Merck Related Item: Paging Dr. Salmon -- It Seems You Are Not Alone.

A long-standing, erstwhile and highly valued (note that he owns at least three graphical avatars, awarded here, long ago) "opinion-leader" contributor to the earliest days of this blog goes by the handle "Salmon". Just search that name, above. [I do trust all that is written under his handle -- so you should, too. Smile.]

After (mostly) skimming those "timeless raindrops, under the rocks from the basement of time"* -- on the beds of my icy rivers silently for lo these last four or five years, Salmon re-surfaced, arching from the golden flecked ripples, this week to mention a biologic called Exondys 51 -- and point us toward it, as part of our new non-Merck (did I say "new"?) coverage. Here is FierceBiotech on it -- but we will await Salmon's definitive take:

. . . .John Jenkins, who runs the FDA’s office for new meds, has not taken kindly to the regulator’s recent, and highly controversial, approval of Sarepta’s Duchenne med Exondys 51 (eteplirsen) after hitting out at bad trials with questionable data.

In a presentation given this week at the NORD summit in Arlington, called “Lessons learned from eteplirsen and other recent rare disease programs,” Jenkins spoke specifically of the biotech’s drug, saying: the “path taken by Sarepta NOT a good model for other development programs.”

A month ago, the FDA approved Exondys 51 against all odds. The approval was considered unlikely because many of the data used to back a speedy approval were based largely on a small study of a dozen children with no placebo control, comparing eteplirsen’s results against historical data in the muscle-wasting disease.

Back in April, an FDA panel of outside experts voted narrowly, 7 to 6, that Sarepta did not provide substantial evidence from “adequate and well-controlled” studies that the drug produced dystrophin at a level that was reasonably likely to produce a clinical benefit. . . .

And there you have it: an approval of -- at least arguably -- a poorly understood biologic. You are up, in comments, Dr. Salmon. Do hit it out of the park for us -- this is one fat hangin' juicy curve-ball, headed right out to the middle of Waveland Avenue. Smile.


* Apologies there -- to the immortal prose of one Norman MacClean.


Federal Propecia®/Proscar® MDL Update: Post Status Conference of October 19, 2016

While I have been quite busy -- joyfully paying close attention to one other particular development, there was a status conference and trial plan update in Brooklyn's federal District courthouse -- in that MDL addressing the erectile dysfunction claims against Kenilworth.

We should know the bellwether trial order, for the first six, by Halloween (and my earlier backgrounder on those cases); here is the rest:

. . . .The parties stated that they are proceeding on track with the schedule set forth in the Second Amended Discovery and Trial Plan PPO 10 [295]. They have submitted their selection of cases for the First Bellwether Tranche, which the Court will endeavor to select on or before October 28, 2016. The Court noted that a Daubert hearing will be held after full briefing, on a date to be determined, as stated in PPO 10 Order paragraph 13. The parties were directed to file a joint status report by March 3, 2017 reporting on the progress of discovery and raising any issues which need to be addressed. . . .

Now you know. What a glorious evening -- sailing straight on (second star to the right), into morning, now. . . Cubs coming home to close out, and head to the Series -- and small banking errands to be completed shortly. Smile. . . .


Thursday, October 20, 2016

Last Night, Merck Had Good Phase III Clinical Trial News, On A Fast-Tracked CMV Antiviral -- AiCuris' Knock-On Effect, Too

This will likely help AiCuris as well, truth told. Back in 2012, AiCuris received a €110 million upfront payment -- from Merck's non-US family of companies. Under the terms of that out-license, AiCuris may receive additional payments if specific milestones are met -- as well as post FDA approval- and market launch- royalty payments. Do go read it all, as linked below.

For now, I'll let FierceBiotech tell the tale:

. . . .[Merck's] fast-tracked antiviral letermovir has hit its primary endpoint in a Phase III test as the partners look to capitalize on Chimerix’s blowup.

The Phase III test was looking at the efficacy and safety of letermovir once daily, in both tab and IV form, for the prevention of clinically significant cytomegalovirus (CMV) infection in patients that are seropositive recipients of an allogeneic hematopoietic stem cell transplant.

Data were not posted, but these will come at a future scientific conference, according to the company. The primary outcome measure was the percentage of participants with clinically significant CMV infection through 24 weeks after transplant.

The med is designed to inhibit the human CMV viral terminase and the Big Pharma got hold of the drug under a deal signed back in 2012 when Merck bought the worldwide rights to develop and sell letermovir from Bayer spinout AiCuris. . . .

Now you know. Even though the weather was a bit gray, and chilly throughout -- it would be hard to imagine a better end to it. Ear to ear grinning, now. And. . . Go Cubbies! Up 1-0 early, in LA. . . . coming to the friendly confines to close it out.


Wednesday, October 19, 2016

Of Two Spacecrafts' Status Tonight -- At Two Different Planets, Products Of Two Continents -- And Questions Still Abound...

UPDATED: 10.20.16 @ 11:55 PM EDT -- It now seems likely that the Schiaparelli lander made a hard landing on Mars. The 'chute seems to have opened, and then detached early, and the retro-rockets fired for only a fraction of the expected duration. All of which -- along with the radio silence -- would largely point toward an obliterating, catastrophic crash on impact. Disappointing news, if it holds up -- to be sure. Yet onward, as ever. [End, updated portion.]

Each of the missions I've recently been reporting upon -- originating on two different continents -- and circling two separate planets, have now had some non-trivial issues in the last 48 hours.

We will be watching keenly, come dawn tomorrow when ESA next updates on its lander. However, a stable orbit for the ESA ExoMars methane gas monitoring orbiter (larger craft, at right in the circle) has been a clear interplanetary space engineering victory. Now we wait for updates:

. . . .The ESOC teams are trying to confirm contact with the Entry, Descent & Landing Demonstrator Module (EDM), Schiaparelli, which entered the Martian atmosphere some 107 minutes after TGO started its own orbit insertion manoeuvre.

The 577-kg EDM was released by the TGO at 14:42 GMT on 16 October. Schiaparelli was programmed to autonomously perform an automated landing sequence, with parachute deployment and front heat shield release between 11 and 7 km, followed by a retrorocket braking starting at 1100 m from the ground, and a final fall from a height of 2 m protected by a crushable structure.

Prior to atmospheric entry at 14:42 GMT, contact via the Giant Metrewave Radio Telescope (GMRT), the world’s largest interferometric array, located near Pune, India, was established just after it began transmitting a beacon signal 75 minutes before reaching the upper layers of the Martian atmosphere. However, the signal was lost some time prior to landing.

A series of windows have been programmed to listen for signals coming from the lander via ESA’S Mars Express and NASA’s Mars Reconnaissance Orbiter (MRO) and Mars Atmosphere & Volatile Evolution (MAVEN) probes. The Giant Metrewave Radio Telescope (GMRT) also has listening slots.

If Schiaparelli reached the surface safely, its batteries should be able to support operations for three to ten days, offering multiple opportunities to re-establish a communication link. . . .

That said -- as to the NASA/JPL mission, it seems Juno will just do its science over longer orbital periods, tacking around Jupiter at 53 days per orbit. Overall, post debate, I am soaring now (even my Cubbies are up -- and up big -- tonight!) -- right along with a sublime shepherd moon that re-emerged, in full. Let us hope these two do too -- as to scientific and engineering capabilities. Fully. Smiles. . . .


What We Expect To See Confirmed -- By ESA -- As Of Noon Eastern Today...

UPDATED: 10.20.16 @ 11:55 PM EDT -- It now seems likely that the Schiaparelli lander made a hard landing on Mars. The 'chute seems to have opened, and then detached early, and the retro-rockets fired for only a fraction of the expected duration. All of which -- along with the radio silence -- would largely point toward an obliterating, catastrophic crash on impact. Disappointing news, if it holds up -- to be sure. Yet onward, as ever. [End, updated portion.]

[Earlier] UPDATE: 1 PM EDT -- still no signal confirming that the Schiaparelli lander has made a safe touch-down, but the Indian tracking station may have been unable to lock on to the signal -- it may be safe; we just don't have proof of it yet. So we are (still) in white knuckle mode, here. [End, updated portion.]

Well -- this is a moment when Europe "dares mighty things." Again. White knuckle time.

And a computer animation of the first non-NASA engineered soft landing on Mars:

ESA LiveStream

[My apologies if that embedded framed link above doesn't work on your browser. Here's a solid in-line link.] Onward, to all of good will. . . a soft landing ahead, and hoping that estimable twisty copper colored space engineering prowess is rewarded -- in Europe, later this morning. . . smile. . . .


Tuesday, October 18, 2016

European Space Agency To "Drop A Package By" Mars Overnight: ExoMars & Schiaparelli...

At about the same time this post comes online, the main engine burn -- to slow the ExoMars probe into a safe capture orbit -- will have begun.

I'll have more in the early morning, tomorrow, depending on how the ESA engineering effort turns out. Here's a bit:

. . . .As for Schiaparelli, its role is just to land intact. Its only mission is to demonstrate that ESA and Roscosmos have the necessary technology to safely land scientific hardware on Mars. That’s key for the next phase of the ExoMars mission, which involves landing a 680-pound rover on the Red Planet in 2021 to explore the surface and look for signs of biological life. The same technologies used to land Schiaparelli will be used to land the ExoMars rover as well. . . .

We wish them -- and in truth, all wayward shepherd moon-lettes -- the best of luck. . . . I'll be right here, waiting. After-all, it is a vast, wonderful but cold, dark ocean out there, and this is but a tiny row-boat, to be sure. Smile. . . .

[Oh, and as a post scriptum -- Kenilworth has opened a bio-similars explainer website (with differing portals for doctors, patients and insurers -- and differing content) -- to help educate various audiences, about this important part of the cost-constrained, emerging medical delivery landscape (and a part in which Merck plays an increasingly active role). Now you know.]


Monday, October 17, 2016

More News Due From Jupiter: JPL/NASA Juno Team Will Conduct A Press Briefing -- On Valve Glitch -- Late Afternoon Eastern, On Wednesday

As we were first to report, world web-wide it seems, on this past Saturday morning -- the basketball court sized Juno orbiter has experienced a bit of a hiccup.

I don't expect this small glitch to interfere with any of the main science mission -- but that is why NASA is briefing the press, come Wednesday. Either they've solved the glitch, or they've figured out that both the involved valve's main circuit, and/or backup circuit(s) are likely fried. I expect we will hear that the mission is still all green lights, either way. In any event, here are the press conference details -- it will be streamed over live NASA TV, as well:

. . . .Team members of NASA’s Juno mission to Jupiter will discuss the latest science results, an amateur imaging processing campaign, and the recent decision to postpone a scheduled burn of its main engine, during a media briefing at 4 p.m. EDT Wednesday, Oct. 19. The briefing will air live on NASA Television and stream on the agency’s website. . . .

The briefing will take place at the meeting of the American Astronomical Society’s (AAS) Division of Planetary Sciences and European Planetary Science Congress (DPS/EPSC) at the Pasadena Convention Center in Pasadena, California. To attend the Juno briefing in person, media should request a press registration form at the event registration desk.

For access to the event live webcast, media should send their name and media affiliation to AAS Press Officer Rick Fienberg at, or call 857-891-5649, by 1 p.m. Wednesday. . . .

I'll try to catch the replay late night on Wednesday night, or early Thursday morning, like 1 AM EDT -- on NASA-TV. . . since all my daylight hours are now spoken for. As ever -- onward she sails, that mysteriously vexing, ever intoxicating twisty copper colored shepherd moon-lette, blissfully unaware of any potential peril that might befall my mission. And that, her unwasted grace, is noble too, in its own way. . . smile. . . .


Sunday, October 16, 2016

Fascinating: Some Ancient WW II History Means Merck's Choice Of Law Argument Will Likely Prevail

[Ahem -- check the new masthead -- it tells a new story, and will likely mean the continuance of this blog, in some form.] Now, in the ongoing multi-national litigation about an old 1970 agreement, on the contours of the rights to use the term "Merck" -- by the German company, and the US based one -- an even older bit of history, will now likely control this rather arcane "third year of law school" question. [Most students take "conflicts of laws/choice of law" in their third year.] Even though this is no longer solely a Merck-focused blog, I was captivated by these new details -- ones I never knew. [So we start our run, as a non-Merck focused blog -- with a Merck focused post. Irony -- that's for me (no more alts., though). . . smile.]

It turns out that in the argument over whether US (New Jersey) law, or German law should govern how the agreement is interpreted, the US government (during World War II) stepped in under the Sherman Act, and had a judge invalidate a prior version of the agreement -- as an unlawful restraint of trade. Much has happened since, but the general principle is that this action for violation of the subsequent 1970 contract was brought in the US, has long been interpreted in the US, and in fact was negotiated at a ABA meeting in St. Louis, Missouri, several decades ago -- by the GCs of each company. I think it likely that US law will govern. [I say this despite the fact that German law is governing the French lawsuit, and UK law is governing the British one. Those make out different claims under local "country-by-country" law.] Here's Friday's filing -- a 31 page PDF -- and the bit that caught my eye, below:

. . . .The earliest Agreement between the parties was entered into in 1932 ("1932 Agreement"). The 1932 Agreement recognized the right of Merck’s predecessors (“Merck Predecessors”) to the term “MERCK” in the United States, its territories and dependencies and Canada, and the right of KGaA’s predecessors (“KGaA Predecessors”) to the term “MERCK” in the rest of the world, with certain designated shared territories. See Exhibit D.

In 1943, the U.S. Department of Justice filed a civil complaint in the District Court for the District of New Jersey under the Sherman Anti-Trust Act alleging that the 1932 Agreement was an unlawful contract in restraint of trade. In 1945, Judge Forman, Judge of the District Court in Trenton, New Jersey at the time, issued a Final Judgment (the “1945 Decree”) cancelling the 1932 Agreement and requiring that Merck Predecessors notify the Department of Justice of any intention to enter into arrangements or agreements with KGaA Predecessors. Section VII of the 1945 Decree, see Exhibit E. Judge Forman also expressly retained this Court’s jurisdiction over the enforcement of the 1945 Decree:

"Jurisdiction of this cause is retained for the purpose of enabling any of the parties to this decree to apply to the Court at any time for such further orders and directions as may be necessary or appropriate for the construction or carrying out of this decree, for the amendment, modification, or termination of any of the provisions thereof, for the enforcement of compliance therewith and for the punishment of violations thereof. . . ."

So, the parties apparently could not reach agreement on choice of law, as I had earlier guessed they might. All of that would seem to militate in favor of retaining US law as the law governing this Lanham Act, and contract breaches claim -- in the New Jersey federal District courthouse.

A decision will be forthcoming in the next few weeks, by the able judge. Off for a workout, on a gray but warm Sunday late-morning here. Hang in there you little copper colored twisty shepherd moon-lette!


Saturday, October 15, 2016

As Oft' Happens -- A Smallish (Potential) Mission Glitch Emerges -- For NASA JPL's Juno Spacecraft...

Considering the harsh environment (crazy hot radiation @ 20 million RAD; a magnetic field 20,000 times stronger than Earth's -- and mostly minus 280 degrees Fahrenheit, hurtling 163,000 mph through space), at 520 million miles from an Earth repair (when it takes over 48 minutes one-way, for data traveling at the speed of light, to reach it) -- this is, I suppose, to be expected. [Earlier backgrounder here.]

Overnight, NASA and Cal Poly's JPL announced that the basketball-court sized Juno spacecraft will stay in its longer, more elliptical orbit (taking another 53 days to loop around the top of Jupiter) for one additional pass at least. Thus the tightening of its belt around Jupiter, to around 14 Earth-days per loop -- will have to wait a tic. Or a tock.

The craft will still collect all the expected data -- and is in a stable position to keep the mission rolling, but if the glitch is not solved, it may take several more months (at the longer 53 days per loop) to garner a statistically meaningful amount of data on what lies beneath those wildly boiling Jovian cloud-tops. [The spacecraft gets just completely hammered by massive doses of Jovian radiation, each time it dips in close -- to those tempestuous clouds. Perhaps the valve controller circuits (including backup controller circuits) have already been mostly fried.]

Here is the full release -- and a bit:

. . . .The decision was made in order to further study the performance of a set of valves that are part of the spacecraft’s fuel pressurization system. The period reduction maneuver was the final scheduled burn of Juno’s main engine.

"Telemetry indicates that two helium check valves that play an important role in the firing of the spacecraft’s main engine did not operate as expected during a command sequence that was initiated yesterday,” said Rick Nybakken, Juno project manager at NASA's Jet Propulsion Laboratory in Pasadena, California. “The valves should have opened in a few seconds, but it took several minutes. We need to better understand this issue before moving forward with a burn of the main engine.”

After consulting with Lockheed Martin Space Systems of Denver and NASA Headquarters, Washington, the project decided to delay the PRM maneuver at least one orbit. The most efficient time to perform such a burn is when the spacecraft is at the part of its orbit which is closest to the planet. The next opportunity for the burn would be during its close flyby of Jupiter on Dec. 11. . . .

[It has occurred to me (over my Saturday morning coffee and a banana) that I may still write on some ancillary matters related to pharma and life sciences -- and of course, my beloved space sciences -- mostly on weekends. So do look for more robust activity -- on weekends here, from time to time. We will keep a good thought for the solving of this glitch, if a glitch it be.]

Even so, she herself is sailing right along now, entirely care-free, with one other copper colored, twisting shepherd moon-lette I have long admired, mostly from afar. Smile. . . .


Friday, October 14, 2016

In Which Mr. Shkreli Tries To Jam Up A Pub -- Unannounced... Oh -- And A Crim. Pro. Update From Brooklyn

As to Mr. Greebel, there are still a few wrinkles left -- but as to Mr. Shkreli, it seems the parties worked out all matters related to the former need for a bill of particulars. I'll attach the two page letter that pre-dated the agreement entered today, by a day -- so the readers may see just what level of specificity Mr. Brafman was asking from the government -- and he has now apparently received the same.

Here is the order, as entered today, in Brooklyn's federal District courthouse:

. . .Defendant Shkreli and the Government advised the court that the issues raised in Shkreli's Motion for a Bill of Particulars have been resolved. . . .

As only Mr. Shkreli might, as he left court, he then ("his treat!") invited his Twitter followers out for a beer (but perhaps only to the extent that any of them are more than 11 years old).

Then, the pub he named told him -- and his "fans" -- they were not welcome at the pub.

He apparently found another venue, but what sort of a tool tries to show up to a tiny neighborhood bar -- with at least the potential of some 5,000 people -- unannounced?

Naturally -- only Martin. Only Martin the cad-oh-so feckless.

Keep it spinning in good karma folks -- g'night -- truly a fine day's end, indeed!


Thursday, October 13, 2016

FLOTUS Michelle Obama Just Closed Out -- On Donald Trump. He's A Pig. And He's... Toast.

Her voice clearly quaking with rage -- she has just buried Donald Trump, alive. She is truly the preeminent closer on the planet. Do watch all three minutes below.

I may not frequent these parts much, any longer -- so this will serve as a final mile-marker, in how I see the race.

Good riddance, Donald Trump. So many people could learn so much, if they could just listen. . . listen to her.


Wednesday, October 12, 2016

O/T: Heisenberg's Uncertainty Principle -- In Action -- Or... Not. Smile

Well. . . after about 3.8 million page-views, and well-over 2 million distinct viewers -- over the last several years -- this effort may be drawing to a close.

As only ironic fates might have it, it looks like my new law firm will be engaged to represent a company that I have previously blogged about (anonymously), here. And so, this commentary may well now fall silent.

As is true with other matters governed by Heisenberg's sublime theorem, this may all change, upon additional observation and reflection -- as we unfold, at the new digs -- and inspect our merged capabilities.

And, if we don't speak again, do keep it all spinning in good karma. I will still write from time to time, at the satellite sites set forth in the left margin (as I had seen this coming, for a bit now). Do travel well -- and do travel light. For we need not live high -- to live well. . . . It's been a privilege.


Tuesday, October 11, 2016

USDC ND CA -- Post Trial Briefing Schedule Extended: Gilead Vs. Merck -- On Amount Of Legal Fees & Expenses Merck Will Have To pay To Gilead

We have long covered this portion of the bi-coastal US patent fights between Merck and Gilead -- over the effects of some basic Merck Hep C sofosbivur patents -- and the purported need for Gilead to license those patents, and pay a royalty to Kenilworth -- in order to be able to sell Sovaldi® and Harvoni®, in the US.

The post trial briefing on how much of Gilead's legal fees Merck will be ordred to pay has been stretched a bit -- in an order just entered in San Jose, California -- thus:

. . . .Oct. 14, 2016 | Oct. 28, 2016 | Gilead files opening brief regarding amount of fees award

Nov. 4, 2016 | Nov. 18, 2016 | Merck files opposition brief regarding amount of fees award

Nov. 18, 2016 | Dec. 2, 2016 | Gilead files reply brief regarding amount of fees award. . . .

And. . . Go Cubs GO -- close out the Giants!


Reuters' Paratek-To-Merck-Vs.-Hospira Patent Reporting: Confused -- But I'm Out Of Time, Today.

The usually reliable Reuters service put out an overnight story -- on Hospira's attempts (now owned by Pfizer) to launch a generic version of Invanz® (purporting to cover the patent spats involved) -- that is (at best) confusing.

Here is the full memorandum opinion (a 49 page PDF file) from last Friday in Delaware federal District Court.

You should read it for yourself -- but the upshot is that it will be immaterial to Kenilworth.

If and when I find some quiet time, I'll be back to explain what's really going on here. Until then -- best to all. As ever, life intervenes -- smile. . .


Monday, October 10, 2016

In One Kind Of Cancer, Opdivo® "Hits A Bump" -- While Merck's Keytruda® Study "Looked Past" Three-Quarters Of The Same Lung Cancer Patient-Sets

I'll try to be brief, as I am still a bit groggy from my travels [and just awakening, truth be told -- and I have listened to no one's webcasts(!)]. When I rolled over to see how much BMS was off on the NYSE, at open, I felt it was at least a bit of an over-reaction to the actual news contained in the unlikely pairing -- of competing study discussions, in Copenhagen over the weekend. [Backgrounder, in which I predicted this past weekend's state of affairs, here (from early April 2016).] Why do I feel that way? Because we are talking about one cancer -- of dozens -- and one subset of patients in that one cancer. [That said, is a very heavy burden cancer, that I will freely grant you.]

First, let's start with Merck, since this is a Merck blog: Merck's latest strong first line NSCLC data is certainly good news for it. Having said that, Merck's study turned out well in more than a little part because of smart study design: it excluded about three quarters of NSCLC patients from being eligible for its study, choosing only those who were most likely to show a strong benefit, after a diagnostic test. And a strong benefit it saw. But to perhaps oversell the analogy a bit, Merck vastly narrowed its implied market in first line NSCLC -- by setting the entry bar for the study so, so high. It will corner the one quarter of front line NSCLC patients who express high levels (>50%) of a predictive ligand.

Meanwhile, the Opdivo study may have suffered from a less-than-optimal study design, making it very hard to tease out secondary lessons -- but it did stub its clincal trial jacket's toe. I still suspect, however, that when the dust settles, both companies' agents will be required to run diagnostic testing in first line NSCLC patients before an insurer or government payer will approve either, as a course of therapy.

And as bigger study results for Opdivo emerge -- I suspect the data will show the two are roughly comparable in this setting. But there are many other studies, in other cancers, where BMS looks to have the lead. Moreover, BMS continues to swing for the fences with its studies, while Merck is hitting solid singles and an occasional double.

In sum, I do not think this single (unrelated) coupling of studies fundamentally changed the game, in the wide azure ocean of immuno-oncology -- that some pundits are claiming. Except, of course, in one quarter of first-line NSCLC patients. And that may well dissipate in time -- with more data. But none of us have that data yet. So congrats go out to Kenilworth.


Friday, October 7, 2016

Some Bright Fall Friday Morning Trivial Lunacy: For People Who'd (Thankfully) Forgotten Martin Shkreli Ever Existed...

I'll repeat only the smallest bit of it, below -- but if you'd like to see what happens when someone's 15 minutes of notorious media coverage (not fame, in any real sense) draws to a bitter, sad end -- do click on through. With colleagues, we are covering it, in roughly real time.

But do be warned -- most of what that lil' guy has to say. . . is retch-worthy. Let's listen to Mr. Shkreli, tweeting in what absolutely must be a nasally high, entitled lil' chicken-chested white guy (faux street) voice:

. . . .it takes restraint of Christ himself to not have these rookies touched–i promised my pretrial officer i’d calm down but yall got me turnt. . . .

ill leave u rekt in the street with broken bonez if u keep talking ish to me you fuck boy. wtf would you know about anything. my money long. . . .

— Martin Shkreli | Oct. 4, 2016. . .

Ugh. A cringe-worthy lil' cretin, is he -- indeed. But for my part, it is onward, to a beautiful Fall morning's walk in, and a busy traveling long weekend. Be well, one and all. . . .


Thursday, October 6, 2016

Propecia®/Proscar® MDL Update: Today, The Initial Six Bellwether Cases Have Been Suggested -- With Three Per Side

In the federal District courthouse in Brooklyn this afternoon (as we indicated they would, last week), both Merck, and the plaintiffs' lead counsels revealed their three (cherry-) picked cases. Well, they each revealed them to the able trial court judge, Brian M. Cogan I should more properly say. Of course, where erectile dysfunction is among the alleged off-target / side-effects, it makes quite a bit of sense that some plaintiffs might prefer not to be identified by name, in the public record -- any more than absolutely required, to allow the cases to proceed. Indeed, there are very important health care/personal privacy interests at stake here.

In view of that, both sides then immediately filed mirroring motions to seal the names and all other details of the three cases each had selected. Judge Cogan provisionally granted those "stereo" motions, this evening -- subject to his determining that the sealing is appropriate, upon review of the involved papers -- and still addresses any concerns about a free press, and the general preference for open access to our federal courts. That said, I suspect the names will remain sealed. These cases are more sensitive, in my view, than the Vioxx, the Fosamax or NuvaRing ones -- given that a central claim of most of these male plaintiffs is a permanent (or at least long-lasting) reduction in their manhoods' firmness.

For our part, we hereby resolve not to name any plaintiff, unless a given named plaintiff consents in writing to the contrary -- after either (i) an appropriate court order, or (ii) proof of identity, attached to the consent. Here is the full text of tonight's order:

. . . .ORDER granting Motion to Seal, subject to the Court's review of the sealed materials after it has been filed so the Court can determine whether sealing is necessary. Ordered by Judge Brian M. Cogan on 10/6/2016. . . .

And so, the federal MDL stays on track to hold a first bellwether trial -- as early as September 2017, or about a year from now. The state consolidated action (in New Jersey) will start similar "test case" trials no earlier than April 2018, in all likelihood. Now you know -- so sleep well, one and all. . . . like little round river rocks. A busy day lies ahead, on the 'morrow. Smile. . . .