Merck Q3 2016 Earnings Call — At 8 AM EDT Tomorrow

October 24, 2016 - Leave a Response

It is unlikely that we will live blog it, but you may tune in yourself.

I expect an in-line quarter. So, do click here. . . .

Be excellent to one another — and keep the Universe spinnin’ in good karma. . .


As Expected. Merck’s Lobby Spend Declined In Q3 2016 — Presidential Election Year

October 24, 2016 - Leave a Response

As we’ve mentioned before, the usual trend in “regular” lobby spending in pharma at least, is to see a decrease during the heart of each four year Presidential cycle. Things pending in Congress tend to go quiet — on the lobbying front — as the mad dash to the finish unfolds.

That pattern is holding again this cycle, as it did in 2008 and 2012. [And, overall, Merck’s lobby spend is on a downward trajectory, of late.] Three years’ worth of detailed Q3 trend-line is at right; here is what the decreased amount was spent upon:

. . . .340B (no specific bill), Hepatitis C (general education; no specific bill), Human papilloma virus and vaccine policies (general education), shingles vaccine policies (general education), antimicrobial resistance (general education and DISARM (H.R. 4187), biosimilars (no specific bill), 21st Century Cures (H.R.6), Senate Innovation Project (no bill number), cost and value of medicines (no specific bill), priority review voucher, biodefense and medical countermeasures (general education), women’s health (general education), Prescription Drug User Fee Act (PDUFA; general education), Affordable Care Act, S. 3056 (CREATES Act), risk evaluation and mitigation strategies (general education), general pharmaceutical issues. . . .

Animal health vaccines, FMD vaccine bank, USDA rule for categorical exclusions for animal health vaccines, FDA guidance 209-213, FDA rule regarding species-specific antibiotics data collection, Animal Drug User Fee Act. . . .

Comprehensive tax reform (no specific bill), House Republican tax blueprint, international tax proposals (no specific bill), orphan drug legislation (HR 3678). . . .

Trans-Pacific Partnership, data exclusivity for biologics. . . .

Patent settlements/pay for delay (general education). . . .

Now. . . when (not if) HRC wins the White House in a few weeks, I would expect Merck’s lobby spend to ramp up, as the next wave of health care delivery reforms rolls through the new Congress. Now you know. And. . . beginning a clear, gorgeous Monday, with hope — hope that a long and beautiful friendship has been revived. Smile.


[U] “Salmon, Rising” — Sarepta’s Exondys 51® [Eteplirsen]: For Duchenne MD

October 23, 2016 - Leave a Response

life-sarepta-salmon-2016 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.


Last Appearance: 1945; Last World Series Championship: 1908

October 22, 2016 - Leave a Response

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?

October 22, 2016 - Leave a Response

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 he is suing AudioEye, in retribution. That’s the Condor guess.

Yep — that’s my thought. Now you know. And. . . Go Cubs Go!


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

October 21, 2016 - Leave a Response

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 rather 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. Goodbye, Mr. Spaulding! Smile.


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


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

October 21, 2016 - Leave a Response

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. . . .


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

October 20, 2016 - Leave a Response

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.


Of Two Spacecrafts’ Status Tonight — At Two Different Planets, Products Of Two Continents — And Questions Still Abound…

October 19, 2016 - Leave a Response

life-jupiter-mars-2016UPDATED: 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…

October 19, 2016 - Leave a Response

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. . . .