O/T Kentucky Edition: It's All Over -- Except The Shouting, Now. . .

I'll note -- as I depart the office for the day -- that the State of Kentucky's latest salvo of responses to Kim Davis' completely baseless (and tediously repetitious) claims (those having been ginned up by Liberty Law) are now public record in the Eastern District courthouse.

What there appears is a state increasingly (and justifiably) frustrated by a George Wallace like refusal to follow the now-settled law of the land. Here's a bit of what we find (a 17 page PDF file), in the moving papers:

. . . .[A]ny liberty interest Davis might possibly have as a private citizen does not extend to her role as a governmental official. Even if KRS 446.350 were somehow to apply to Davis, it cannot apply in her official capacity as the Rowan County Clerk because accommodating her in the manner she suggests would amount to a violation of the [federal First Amendment] Establishment Clause. . . .

Davis asserts that had the Beshear Letter not been issued, the plaintiffs "would have had to sue Gov. Beshear (not Davis)" to obtain their marriage licenses. See Response at 14 (D.E. 123). This incredible statement demonstrates Davis’ stubborn disregard for the rule of law. Obergefell held that the plaintiffs have a fundamental right to marriage. Following Obergefell, they should not have been required to sue anyone in order to exercise that right. Of course, Davis ensured that was not the case in Rowan County. . . .

When an official such as Davis acts in her official capacity to perform an obligation imposed by law, she is acting as the government. Cf. Kentucky v. Graham, 473 U.S. 159 (1985); KRS 62.210 ("[t]he office of county clerk, rather than the individual holder of the office, shall be liable for acts or omissions of deputy clerks"). At issue here are marriage licenses issued by the Office of Rowan County Clerk and not Kim Davis individually, as Kim Davis individually has no authority to issue such licenses. The Office of Rowan County Clerk does not have a right to free exercise of religion. If government officials were permitted to exercise religion in their official capacity, such action would directly violate the Establishment Clause, which prohibits governments from favoring or promoting one set of religious beliefs over another. . . .

[Issuing a marriage license] is a ministerial act statutorily required of the Office of Rowan County Clerk. The issuance of a marriage license simply certifies that the couple satisfies the legal prerequisites for marriage. KRS 402.100. To the extent the issuance of marriage licenses constitutes speech, it is attributable to the government and not Davis. . . . [Even for argument sake, if we assume it was speech] "restricting speech that owes its existence to a public employee’s professional responsibilities does not infringe any liberties the employee might have enjoyed as a private citizen." Garcetti, 547 U.S. at 421-22. . . .

She has no standing -- so true. Onward. Smile. . . .

"Some Days, This Stuff Just Writes Itself": Reprised From September 2009

Given the propensity of Mr. Shkreli to continue to damage his private company's brand -- and his own meager credibility -- in the last two weeks, I thought it would be useful to rerun my September 2009 piece -- on his "Godpharma" -- one fast Fred Hassan. Mr. Hassan did pretty much the same, by blogging -- in intemperate fashion -- in those days. Morever, the two were thick as thieves not long after this post -- as Hassan was investing in, and guiding the young Shkreli (albeit at his former company), according to numerous MSM published reports. So here it is, in full (I did update the graphic, a bit, though -- at right):

Some days, this blog just writes itself. Today is one of them, per the WSJ Health Blog:

. . . .Ever since Merck announced it was taking over rival Schering-Plough, inquiring minds have wanted to know: What will Schering-Plough CEO Fred Hassan do next?

Perhaps now we have a clue: Hassan is joining us bloggers, at least for some of his time.

In a Huffington Post piece, Hassan weighed in yesterday on the health-care debate, arguing that the discussion has unwisely ignored serious and long-term threats such as Alzheimer’s disease. . . .

The deal for the very-life of his company hangs in the balance. . . and he is off, blogging? Cool. I can FINALLY relate.


Credit for the original work on the fabulous graphic, at right, goes to "The Insider" PharmaGossip.

Overall, though -- sometimes, the truth is far stranger than anything we could make up. . . . This is one of those times, for dead certain (Kudos to The Insider!):



The music in that clip is (given the subject matter, to my ear, at least). . . soul-less, overwrought and sinister. . . perfectly evocative, of the 2015 -- and 2009 -- versions, no? Onward, just the same.

BMS -- And Opdivo® -- Well Ahead In Kidney Cancers @ ECCO 2015

Over the weekend (through to tonight), in Vienna, Austria, the ECCO (or European Cancer Conference) has been underway.

Just as we said it would, back in July 2015, BMS's nivolumab has pretty much turned out to be the belle of the ball. Advanced renal (kidney) cancer is generally a pretty dire prognosis. But on Opdivo^®, such patients saw on average, two years of added survival time -- and that led researchers to end the study very early, and give all comers the study drug -- for obvious ethical reasons.

This doesn't mean Merck won't eventually get Keytruda^® approved for kidney cancer -- but it does mean BMS is at least a year ahead. And it means that BMS is racking up lots of heavy burden of disease cancers -- as the likely first mover. Here's a bit from the New York Times, of Saturday:

. . . .[A] study of the drug nivolumab (sold as Opdivo), was stopped ahead of schedule because safety monitors found that patients receiving the drug were living longer than those in a comparison group taking the usual treatment, everolimus (sold as Afinitor). The study was halted for ethical reasons, to offer the comparison group nivolumab. . . .

Nivolumab belongs to a class of drugs called immune checkpoint inhibitors, which work by unleashing the patient’s own immune system to fight cancer. The new study included 821 patients with advanced kidney cancer. Half received nivolumab, and half everolimus. Of all who got nivolumab, 25 percent responded, meaning their tumors shrank significantly; only 5 percent responded to everolimus.

With nivolumab, the median survival was 25 months, compared with 19.6 months for everolimus. Patients taking nivolumab were also more likely to have lasting responses and fewer side effects like fatigue and nausea. . . .

Onward on a lovely fall Monday -- one on which liquid (albeit briny) water has just been found to be presently flowing on. . . Mars. And that makes some form of life. . . at least a slightly closer possibility, there. What a time we are privileged to be living in. . . . Whoosh!

Even As PhRMA Declares "Shkreli Is NOT One Of Ours" -- It Elects A New Chief; Former Device Lobbyist Ubl

Earlier this week, both BIO and PhRMA -- likely sensing a PR disaster in the making -- openly disavowed Martin Shkreli. PhRMA declared that privately held Turning Pharmaceuticals, and Martin Shkreli, are not, and were not members, and "did not reflect" the trade group's "values or views." This was a wise first step, I think.

But now, PhRMA -- chaired through April 2016 by Merck's Kenneth C. Frazier -- has tapped a legendary medical device lobbyist (understated and pragmatic, is Ubl) to lead PhRMA through these almost certainly more widely-emerging US firestorms -- on pharmaceuticals pricing (even without regard to whether Hilary Clinton is ultimately able to win wider backing for price controls).

From the New York Times, overnight:

. . . .For the last 10 years, Mr. Ubl has been the top lobbyist for medical device makers. He has led efforts to persuade Congress to repeal a tax on medical devices imposed by the Affordable Care Act.

Mr. Ubl, 46, is well known in Washington for his deep knowledge of health policy, shrewd political instincts and low-key manner that sets him apart from many lobbyists.

His selection was announced by Kenneth C. Frazier, the chairman of Merck, who is also chairman of the pharmaceutical trade group.

Some people who have worked with Mr. Ubl said he might be open to pragmatic pro-consumer compromises, but some consumer advocates said he had not been receptive to their appeals for help in recent years.

Marc M. Boutin, the chief executive of the National Health Council, a coalition of advocacy groups for people with chronic diseases, said Mr. Ubl had been a strong ally. As a member of the council’s board from 2008 to 2013, Mr. Ubl helped patients influence the writing of the health care law and the way it has been carried out, Mr. Boutin said. . . .

Almost trivially, I'll note that a NYC punk rock recording label has also cut all ties with Shkreli (he was reputedly an early angel investor). I'm pretty sure he did not expect that following Fred Hassan's playbook would make him such a pariah. But it is 2007 no longer, friends. Health care reform is here to stay. How the world turns. . . Onward, with a grin. . . .

"Bad Boy Du Jour" Shkreli? Just Fred Hassan's World-View -- Taken To Its Logical Conclusion. . .

You simply must read Matt Herper in Forbes this morning. He is 100 per cent right: sociopath. "Iconoclast"? I think not.

He has written the definitive take-down of the Turing CEO's latest 5,000 per cent price gouging. Go read it -- more in a minute -- but Matt's got this to say about that CEO's mentor/teacher, Fred Hassan:

. . . ."The only person I needed affirmation from was Fred Hassan," Shkreli told me during our first meeting. "So I asked [Hassan and Saunders] do you think I can do this? They said you must do this. We really want you to do this."

Saunders, who is now the chief executive of Allergan, says that the team chipped in to help Shkreli buy the technology [at his former company, Retrophin], but lost interest as Shkreli changed focused more on drug pricing. Saunders and another former Schering executive, Robert Bertolini, say Shkreli listed Saunders as a member of Retrophin’s board of directors on the company’s web site without, in Saunders’ words, "my consent, knowledge, or permission." Bertolini says Saunders was furious at the time, but Shkreli claims that Saunders agreed to be on the board but never finished any paperwork. . . .

That behavior matches Shkreli’s Internet persona. He’ll Tweet vulgar quotes from Wu-Tang Clan and Eminem songs, and he helped ignite the current controversy by calling John Carroll, the editor of industry news site FiercePharma, a “moron.” Shkreli claims he doesn’t care what the media or the public thinks, but he has an almost pathological need to respond to what is said about him, and lacks the good sense, so ingrained in most chief executives, to know when not to talk. . . . Whether Shkreli can keep doing his job with a giant target painted on him is an open question. . . .

And, to be clear, John Carroll is -- in my experienced opinion -- a smart, thoughtful and independent man. Too bad Shkreli cannot see that.

I've said it so many times before -- Saunders is (in my experienced opinion) just a milder version of Shkreli -- both taught their particular version of deal-craft skull-duggery, by Ex Schering-Plough CEO "Fast" Fred Hassan. His world-view leads to these abberant next-gen pharma CEOs. But at least the Turing CEO has now been definitively unmasked, thanks in no small part to Matt. [And to that CEO's own over the top idiocy.] How long until Brent is? That's a question for the ages. . . [Fred pretty much has been -- and is. . . a has been.] Onward, in any event, on a lovely fall noon-time. . . .

Even With Good R&D News, JP Morgan Crimps Merck Price Target A Bit

JP Morgan is keeping Merck at an "Overweight" rating, but has trimmed its 12 month price goal, to $65 -- crimped from $68. You'll recall that Piper Jaffray made a similar move -- dropping Merck to a $60 target -- last week.

And yet, this comes amid good pivotal C. difficile clinical results, from Sunday. Add to this that this morning, Merck announced a wide array of new "hard tp treat" cancer programs data sets will be appear shortly -- for Kenilworth's pembrolizumab onslaught of programs.

Of course, the counter-argument -- on C. difficile treatment -- is that a capsule of purified stool sample is doing pretty much the same thing, in trials, at a potentially much lower price point. On pembrolizumab, BMS is a very strong first mover, with Opdivo^®. And perhaps of the greatest near term importance, the Merck sitiglipin franchise is likely to be pressured by the Jardiance^® home run data sets, into 2016. So it goes -- here's the bit:

. . . .Merck had its target price lowered by JPMorgan Chase & Co. from $68.00 to $65.00 in a research note issued to investors on Monday, MarketBeat.com reports. The brokerage currently has an "overweight" rating on the stock. JPMorgan Chase & Co.’s price objective would suggest a potential upside of 24.69% from the stock’s previous close.. . .

We will watch the horizon, here -- as ever. Have a great evening, one and all.

Passengers Arriving In US From Liberia Will No Longer Be Screened For Ebola: CDC

I offer this as some additional encouraging positive proof that the current threat has passed -- at least as to the 2014 epicenter of Liberia -- which has been completely disease free, since September 3, 2015. U.S. Customs and other border authority agencies will no longer routinely screen arriving passengers from Liberia for the virus. Screenings will continue (at least for now), for passengers arriving from Sierra Leone and Guinea, however.

Here is the bit -- as reprinted by Time magazine's Monday edition:

. . . .Federal agencies have decided to end the mandatory screening for air travelers arriving in the U.S. via Liberia, effective Monday.

The Centers for Disease Control and Prevention (CDC) and Customs and Borders Protection decided to remove Liberia from its list of countries requiring additional screening, USA Today reports. The screening, in which travelers fill out questionnaires and have their temperatures checked, is currently conducted at five airports in the U.S. that service connecting flights from West Africa.

The World Health Organization declared Liberia, once at the epicenter of the Ebola outbreak, free of the disease earlier this month on Sept. 3. . . .

Onward, with a smile. . .on yet another perfect early fall Sunday -- here, in the City of Big Shoulders. . . .

O/T -- Kentucky Marriage Equality Matter, Back In Judge Bunning's US District Court, Come Tuesday. . .

More in a minute, but it seems the intrepid County Clerk, Mrs. Davis, feels the certificates should now read "issued only pursuant federal court order" -- rather than the way they always did.

The state officials see this as a compromise, apparently -- as they suggest this allows Davis to clear her conscience. So, the state says they are still valid certificates. The ACLU suggests these changes may make the certificates of questionable validity -- after all, Kentucky law requires that county-level clerks issue them -- under local authority. And, the ACLU says, these changes are in arguable violation of Judge Bunning's order -- telling the Clerk not to interfere with the orderly certificate issuance process. Here's the full filing -- for the very able Judge Bunning's consideration come Tuesday, and a bit:

. . . .In fact, Davis has modified the marriage licenses currently provided by her office to state that they are issued only "Pursuant to Federal Court Order #15-CY-44 DLB". . . .

Additional material alterations made by Davis to the licenses issued by her office include requiring her clerk to issue licenses in his capacity as a "notary public" rather than a deputy clerk of the Rowan County Clerk’s Office. Id. See also Notice of Filing by Bryan Mason. [RE #114.] These alterations call into question the validity of the marriage licenses issued, create an unconstitutional two tier system of marriage licenses issued in Kentucky and do not comply with the September 3 Order prohibiting Davis from interfering with the issuance of marriage licenses. . . .

So -- we shall see. The notary public nonsense is of no moment -- in my opinion.

It is a closer question as to whether a federal court will order another change to the certificates, once the state officials have declared them valid (even if I hate that the Clerk once again has meddled, to manufacture this latest "showdown" -- between state and federal authorities). It is the duty of the clerk to simply comply with the law. Not clear her conscience. But I suspect this will be the end of it -- Judge Bunning may well just say "she's received too much attention, already. Her 15 minutes are. . . over". Onward -- Have a wonderful Saturday, one and all!

Propecia® MDL -- Slight Delay Until September 25, 2015 -- On Procedural Orders

Well -- we still have no hint about any outcome -- from the show cause hearing held September 10, 2015.

But this afternoon, we do see that the parties have been working to resolve their disagreements -- about the plan for amended discovery procedures, in view of the Court's order on, and observations about, the state of the privilege logs, previously submitted by Merck. So much so, that they need a short continuance to submit an agreed order. That order was due today; now it is due in a week (assuming the Court enters the continuance, as proposed).

While it seems unlikely, I suppose it is at least possible that this amended order will address whatever the issues were that radiated from the appearance of Dr. Imperato-McGinley, in court, last week. In fairness, I would expect that to be the subject of some separate order -- but we shall see. Here is the bit, from the afternoon's proposal for an order:

. . . .The parties are continuing to discuss certain terms of the amended Discovery Plan And Trial Plan Order (PPO No. 10) and requesting that the Court allow them to submit the Order on or before September 25, 2015. . . .

Thus we see that all things worth knowing take a bit in federal court. That will likely apply to the Imperato-McGinley documents (to the extent that there are any more) as well. Have a stellar weekend, one and all of good will -- big triathalon to take in, here!.

As We Previously Predicted, Lilly's SGLT-2 Will Get A Boost, Even As Merck Hits Headwinds -- In Diabetes

Even as Merck was outlining its pipeline, and plans, at the Morgan Stanley confab -- in the diabetes management franchise -- it was actually Lilly's new SGLT-2 drug making the real waves today in that space.

Just as we had directly suggested in August, the cardio-protective side benefit of Lilly's Jardiance^® may well cause a sea-change, among prescribers -- away from Kenilworth's Januvia^®. Here is a bit of the Reuters item, of earlier today:

. . . .Sanford Bernstein analyst Tim Anderson more than tripled his annual sales forecast for Jardiance and combination drugs containing it to $2.7 billion by 2020. He cut his 2020 sales forecast for Merck & Co Inc's Januvia, the leading member of a competing class of oral diabetes drugs called DPP-4 inhibitors, to $6 billion from $7.8 billion.

Anderson estimates Jardiance could boost Lilly's earnings per share by 8 percent on average across 2016 to 2020.

In the study, patients taking Jardiance had a 38 percent reduction in cardiovascular death, including from heart attacks and strokes. There was no significant difference in non-fatal heart attacks or non-fatal strokes. . . .

To be sure, Merck will be fine -- with Keytruda^® (in cancers) off and running, and more than filling the Januvia revenue gap, in years beyond 2016. But in the short term, it may prove to be a bit of a pinch -- at the revenue line, globally. Hooray -- it is almost Friday!

President Obama Makes An Excellent Choice -- To Lead FDA

We have long admired Dr. Califf (as the 2009-vintage graphic at right will attest). Overnight, our 44^th President tapped him to lead the FDA -- where he's been serving as Deputy Commissioner, since Spring.

He is smart, fair, balanced and open minded. In short, a great pick. From the White House presser then:

. . . .President Obama announced his intent to nominate the following individuals to key Administration posts:

Dr. Rob Califf, Nominee for Commissioner of Food and Drugs, Department of Health and Human Services

Dr. Rob Califf is Deputy Commissioner for Medical Products and Tobacco at the Food and Drug Administration (FDA), a position he has held since March 2015. Dr. Califf has served in various capacities at Duke University School of Medicine and the Duke University Medical Center between 1982 and 2015. At Duke University School of Medicine, he served as Vice Chancellor, Director of the Duke Translational Medicine Institute, which he founded in 2006, and as Professor of Medicine. He also served as the Director of the Cardiac Care Unit at the Duke University Medical Center. He founded the Duke University Clinical Research Institute in 2006 and served as its Director. Dr. Califf also served on the Executive Committee of the Duke Health System. He has served in a number professional organizations, including committees of the Institute of Medicine of the National Academies (IOM), the IOM Clinical Research Roundtable, the IOM Committee on Medication Errors, and the IOM Board on Health Sciences Policy. He served on the FDA’s Cardio renal Advisory Committee from 1996 to 2000 and on the FDA’s Science Board Working Group from 2007 to 2008. Dr. Califf received a B.S. and an M.D. from Duke University. . . .

Onward, on a truly flawless morning.

Interesting Statements -- Back When FDA Approved Propecia® (Finasteride) For Hair Loss -- By Dr. Imperato-McGinley

Back when Merck originally sought FDA approval of finasteride for the indication of male pattern baldness, the doctor appeared at the Advisory Committee hearing and spoke for the company. [Merck by then already had obtained FDA approval for prostate enlargement, under the brand name Proscar^® -- but baldness was a much wider market.] She generally noted the safety of the drug candidate for that purpose, and apparently made reference to her earlier work in the Dominican Republic. I mention this because that is what our erstwhile anonymous commenter was pointing to, in the cogent comment to my last post on this topic. Her statements to FDA, on behalf of Merck do make her a likely witness to these matters, in my estimation. So she is likely to be asked quite a few more questions, as discovery rolls forward. She ought to get used to it.

To be fair, though, the FDA still feels that sexual dysfunction is a relatively rare side effect. To wit, recently, the FDA has cleared an update to the finasteride label, and weighed in on these topics. From FDA then, a bit:

. . . .Q5. Do all men experience sexual adverse events when using Propecia or Proscar?

A5. No. Only a small percentage of men using these drugs have experienced a sexual adverse event. The frequency of sexual adverse events is best obtained from controlled clinical trials. Analysis of these controlled clinical trials showed that during treatment with Propecia, 36 (3.8%) of 945 men had reported one or more adverse sexual experiences as compared to 20 (2.1%) of 934 men who did not receive Propecia (received placebo).

Sexual adverse events associated with Proscar use were identified in two clinical trials. This information is included in the Proscar label. In one trial, these events were reported more frequently during the first year of treatment with Proscar as compared to men who received placebo. In years 2-4 of the trial, there was no significant difference between treatment groups in the incidences of impotence, decreased libido and ejaculation disorder. . . .

It should be noted that the Proscar studies mentioned above generally involved much older men -- in short, men more likely to be on other medications which might mask the alleged off-target effects -- as those men might well already be experiencing sexual decreases -- even from the passage of time. The same was generally not true of Propecia candidates -- they tended to be younger and healthier, and so (the plaintiffs' argument runs) were more likely to notice and report any sexual side effects. We shall -- as ever -- see.

UPDATED: 1 PM EDT | 09.15.2015 -- To make the record complete, here is the full five page PDF of the November 19, 1997 Merck letter to FDA that our erstwhile anomymous commenter points us to -- and an image of the part I personally found most interesting, though the opinions of Dr. Imperato-McGinley are quoted a few other times, in that letter:

And still we have no idea what transpired on Thursday, September 10, 2015 -- in Brooklyn. There has been no update to the electronic record, through noon Eastern, here on Tuesday. So. . . onward, with a big smile.

More News: Solvaldi® Patent Spats Scheduling -- In Merck-Gilead Litigation

As Monday draws to a close, with no word on the finasteride hearing of last week, I'll update the status of the potentially material Gilead - Merck patent litigation.

Here is the latest from the very able Judge Burke -- as he tries to have the parties work out a reasonable schedule, given the competing and conflicting criss-cross patchwork field of lawsuits (in which each alleges infringement of one or more of the others' patents). See below -- this is the full text of his oral order entered today at lunchtime:

. . . .IT IS HEREBY ORDERED that the parties shall meet and confer and discuss, in person and/or by telephone, each of the matters listed on Chief Judge Stark's Case Management Checklist ("Checklist"). Within thirty (30) days from the date of this Order, the parties shall jointly file the following:

(i) a copy of the "Checklist" indicating the names of Lead Counsel and Delaware Counsel for each party;

(ii) a proposed Scheduling Order (consistent with the Chief Judge Stark's Revised Patent Form Scheduling Order); and

(iii) a letter, not to exceed three pages, that contains the following:

(a) a description of what this case is about;

(b) the parties' positions regarding the disputes in the proposed Scheduling Order, and

(c) a list of the three most significant topics (other than Scheduling Order disputes) discussed during the parties' review of the Checklist items, along with a brief description as to what was discussed as to those topics.

Thereafter, the Court will schedule an in-person Case Management Conference/Rule 16 Scheduling Conference to be held with Judge Stark and/or Judge Burke.

The Checklist and Revised Patent Form Scheduling Order can be found on this Court's website (www.ded.uscourts.gov/judge/chief-judge-leonard-p-stark).

Ordered by Judge Christopher J. Burke on September 14, 2015. . . .

Sovaldi^® does represent -- potentially, at least -- a several billion dollar patent fight -- just so you know. So much has happened in the year that is marked by today's date, one year ago. . . so much indeed. Smile.

More Of the Back Story -- On Merck's Finasteride Franchise -- And The Dominican Republic Connection

At the outset, I'll note that none of this is material any longer to Merck's consolidated financial fortunes. Even so, I commend this small bit of investigative journalism to those following the finasteride series here -- as we wait for word, about last Thursday's hearing in Brooklyn. I've mentioned in passing the early research Dr. Imperato-McGinley conducted in the 1970s in the Dominican Republic. Here is how at least one MSM outlet is portraying the connection, this Monday morning -- to finasteride.

From the Mens' Journal article, then -- a particularly provocative bit:

. . . .Knowing the drug's origins might prompt some to shy away from it. Finasteride has its roots in the 1970s, when scientists discovered a rare group of men in the Dominican Republic who were born with ambiguous genitalia and often mistakenly raised as girls.

These men possessed other unique traits: They never lost their hair or had prostate problems. This was because they failed to produce an enzyme that converts testosterone to dihydrotestosterone, or DHT.

DHT is critical for fetal development of male genitals, but in adults it impairs hair growth. Enter Merck, which unveiled a compound — finasteride — that slashes DHT levels 70 percent. As Belknap puts it, the drug works by mimicking the sex-steroid profile of pseudohermaphrodites. . . .

Of course, finasteride is the chemical name of the drug Merck ultimately branded as. . . Propecia^® (and, in some geographies, as Proscar^® -- for prostate enlargement).

And now you know why the plaintiffs' lawyers might feel that her work in the Dominican Republic would be relevant to allegations of sexual side effects, via lawsuits -- even if her research in the DR concluded in the 1970s -- and even though Merck's branded drug wasn't cleared for male pattern baldness until 1996 or so. Onward -- Me? I've always been more than happy to play the cards I've been dealt -- in the gene pool department. Smile.

Piper Jaffray Now Rates Merck At "Hold" -- Target $60

This came out last Thursday while I was attending to other professional duties.

Some of the analysts' froth around Merck's near term growth has waned -- now that the sitagliptin franchise is slowing and prembrolizumab is being mightily pressed at roll out by BMS's nivolumab.

. . . .Target: $60

Rated: Hold. . . .

I still see Merck as a solid long term play, even at today's relatively fullsome prices. So, there you have it. Onward -- with a smile.

On Propecia® MDL Observations -- An Interesting Comment, On Backup Site -- And An Answer

This is from a fine comment left on the backup site -- Original Comment:

. . .Thank you for keeping me updated with this pertinent court information. I have recently been following your blog to keep abreast of the MDL status updates.

With regard to Dr. Imperato-McGinley and the document requests- I am not sure what to make of her and the institution’s situation. 21CFR310.303 appears to place the record maintenance burden onto the new drug applicant, while other 21CFR documents require the clinical trial sponsor [not investigator] to explicitly hold certain document types from 2-10 years including financial disclosures and drug receipt/despising. I’m baffled at what she could possibly possess from the clinical trials.

On the other hand- Upon reviewing the the open-label, 5 year follow-up study I took notice to the Discussion regarding finasteride’s Safety, particularly the claims made in the first paragraph which read as: ‘At the end of the five years the percent incidences of reported sexual adverse experiences was less than the percent reported at year 1 …. [and] sexual adverse experiences are reported infrequently with continued use of finasteride’ (1). However, due to the 58% subject drop-out rate from day 0 to the end of year 5 [Editor: Emphasis supplied] this data appears a little fuzzy :

Sexual adverse experiences reported in this study were for impotence, ejaculation disorder, and reduced libido. As stated above there was a 58% subject drop-out rate from day 0 to the end of year 5. Comparing each of these three reported adverse experiences from year-5 against those from year-1yields an decrease incidence for ejaculation disorder (1.7% decrease), a decrease incidence for impotence (39.4%), and a decrease incidence for reduced libido (60.6%). It should be noted however, that such a reduction in subject numbers may not allow for true and accurate ‘excellent safety’ claims to be afforded. For example, the 60.6% reduction in reported libido from subjects day-0 to year-5 decrease in proportion to the 58% drop-out over this interval, while 1.7% decrease for reports of ejaculation disorder, and the 39.4% decrease in the reporting for reduced libido are not so proportional (increases of 34-fold and 1.5-fold, respectively).

I will let the authors of the this 5-year open-label clinical trial also author the final word here: ‘Finasteride to have an excellent safety profile and be well tolerated’.

Moore, E., (1995) Proscar(R): Five-Year Experience Eur Urol. 28:304-309. . . .

And, my answer -- in part:

Quite so, Brian.

Just to be clear, it was (and is) permissible and common for the sponsor (in this case Merck/Schering Plough) to contract with the doctor's institution (here Cornell) to be record keeper, or at least backup record keeper on trials to be submitted as part of FDA approval packets.

In that case, she and her institution might well have relevant records.

Moreover, anyone receiving AERs -- or adverse event reports -- is charged with certain duties to preserve and forward them, especially post FDA approval -- under applicable federal rules.

She as PI (and the institution, as a CRO) might have been contacted by study participants, along these lines.

As ever -- it is fair for the plaintiffs to ask -- they are paying for the copies after all -- and we will see.

UPDATED: I thought I'd offer a little of the FDA's 1996 to 2014-era perspective on all of this, right here -- from a pronouncement related to keeping records on all study participants -- even participants who might withdraw or be disqualified from continuing in the study:

. . .FDA previously addressed the topic of data withdrawal in the preamble to the 1996 final rule providing an exception from informed consent requirements for emergency research, 21 CFR 50.24. In response to a comment that a subject’s legally authorized representative should be allowed to prevent the review of the subject’s data, FDA stated:

“FDA regulations (see, for example, Sec. 312.62 and Sec. 812.140(a)(3)) require investigators to prepare and maintain adequate case histories recording all observations and other data pertinent to the investigation on each individual treated with the drug or exposed to the device. The agency needs all such data in order to be able to determine the safety and effectiveness of the drug or device. The fact of having been in an investigation cannot be taken back. Also, if a subject were able to control the use (inclusion and exclusion) of his or her data, and particularly if the clinical investigation were not blinded, the bias potential would be immense. Thus, the agency rejects this comment because it could prevent FDA from learning of an important effect of the product and significantly bias the results of the investigation” (see comment 95, 61 Federal Register 51498, 51519, October 2, 1996). It should be appreciated that FDA’s response applies to the most potentially difficult situation, that is, studies involving an exception from the informed consent requirements in which subjects, due to a life threatening medical condition, are unable to provide informed consent to participate in the study. Subjects may subsequently withdraw from such studies, but the data collected up to withdrawal may not be removed.

[Also, s]uch review of safety data by sponsors is required by 21 CFR 312.56 and 21 CFR 812.46. . . .

There is particular concern with a study’s reliability when subjects withdraw their data in a non-random way because they are unhappy with their experience, either because they failed to obtain a desired effect or suffered an adverse event. Loss of these subjects’ data could greatly distort effectiveness results and could hide important safety information (for example, toxicity) of a poorly tolerated treatment. Allowing subjects to withdraw data could even provide an opportunity for unscrupulous parties to “improve” study results by selectively encouraging certain subjects to withdraw from a study. . . .

So it goes. . .

Namaste -- and do stop back by! To one and all -- have a great weekend, if we hear nothing from the court today. Smile.

While We Await Word. . . Some Rainy Friday Miscellany

The electronic files contain nothing new on the finasteride MDL hearing of yesterday in Brooklyn yet.

So -- while we wait -- I'll update an earlier item on an Avelox^® series of claims, that have been designated as an MDL, in the District of Minnesota.

You will likely well-recall that Merck's counsel found himself in some hot water, in the Northern District of Illinois, over a perceived failure to comply with the "plain English" notice pleading requirements, under the federal civ pro rules. That case, called Hobbs v. Merck, et al., has been transferred into the MDL in Minnesota -- so we will follow it there. This new coordinated proceeding (established in mid-August) will be known as MDL 2642, and is assigned to the Chief Judge:

. . . .TRANSFER ORDER from the Judicial Panel on Multidistrict Litigation pursuant to 28 U.S.C. § 1407 that the actions listed on Schedule A and pending outside the District of Minnesota are transferred to the District of Minnesota, creating MDL 2642. MDL 2642 assigned to Chief Judge John R. Tunheim. . . .

Now you know. And so we await word on what transpired yesterday in Brooklyn, on the other -- Propecia^® MDL. Onward, with a goofy big grin!

What To Expect Tomorrow, In Brooklyn's USDC -- Propecia® MDL Hearing -- Doctor To Appear?

At the outset: this "internet blog" is affiliated with none of the plaintiffs' steering counsel -- nor any plaintiff, nor to my knowlege, any named counsel in any part of this MDL litigation. I am a mere observer, of the public record documents. A reporter -- if you will. And I claim that privilege -- and that privilege only.

That said, this afternoon, counsel for Dr. Imperato-McGinley filed an affidavit -- the objective of which was to seek permission from the court for the doctor to skip her appearance.

I expect that set of papers (in a highly unusual format, no less) will be unavailing.

I expect (as ordered) the doctor will appear. I expect that the Magistrate Judge's order of late August will stand. So I expect we will learn more -- and perhaps much more -- tomorrow. Now -- a little homework -- only eight pages -- do read the full PDF of the affidavit the doctor filed today, as it offers a glimpse into what is known about the so-called Dominican Republic documents -- from the 1970s. I'll make no prediction about whether those documents will come into play in this litigation. I will reaffirm, however, that the doctor is mistaken -- and frankly, could have no reasonable basis to assert, infer, or let alone offer conjecture to the Court, in a sworn affidavit, that I am affilitated in any way with the plaintiffs' counsel. I am not. Pretty silly. Here's the operative bit, for posterity:

. . . .16. There are internet blogs that claim I am being brought to Court with my counsel to produce records, claims that may have been peddled by Plaintiffs. . . .

Pop the popcorn -- tomorrow ought to be highly entertaining. Do read her background affidavit, though -- to be prepared. Onward. And here's a friendly salute -- to the Weill-Cornell people who've been carpet bombing my site today. Welcome -- do sit a bit. I won't bite. I promise.

Updated: 10 PM EDT -- I should have noted at the top -- that for the purpose of this Brooklyn court proceeding, the doctor has made herself a public figure. That is, her actions have become. . . newsworthy. Failing to answer a federal subpoena she was served in February (even one she says she only received in April). . . makes her a so called "limited purpose public figure". And so it is the privilege of editorial commentary -- on the inactions or actions of a limited purpose public figure I have claimed, under U.S. Free expression jurisprudence. End, update.

Ongoing Nasonex® Patent Spats -- Suing Three Generics At Once -- Leads To A Disqualification Of A Former Apotex Expert Witness Hired By Merck

I think the Lexis/Nexis practice compendiums may be running an item on this development today, but here is my take on it, with backgrounders, and the relevant memorandum order in full -- and an excerpt of it, below. Merck has lost two prior rounds in these battles -- just to be clear, here.

None of this is financially material (any longer) to Kenilworth, since the branded product has faced generic competitors (including -- as we noted -- Apotex) for quite a while now, but it does mark a "too clever, by half" attempt to rope in a formerly opposing science expert witness (in the Apotex NJ I case), and use him as a weapon in these later cases. Cheeky -- but the very able Judge Sue Robinson (in Delaware federal District Court) isn't biting. And so, a chunk of the order from last week, then:

. . . .Despite the knowledge of both Merck and Dr. Cockcroft that he had rendered expert assistance to Apotex in prior litigation involving the '353 patent, Merck engaged the services of Dr. Cockcroft in the above captioned litigation, again in connection with Merck's patent rights that cover Nasonex nasal spray. In this regard, Dr. Cockcroft failed to give notice to Apotex of his engagement by adverse party Merck because he believed that his engagement by Apotex "ended when that case ended," and that the agreement did not limit his "ability to act as a freelance consultant on a permanent basis. . . ."

Moreover, Apotex's confidential information is at a substantial risk of disclosure and/or adverse use, by virtue of the fact that Merck has chosen to pursue simultaneous cases against all three generic manufacturers -- Teva, Amneal, and Apotex -- regarding the '353 patent. In this regard, common sense dictates that generic products (even pharmaceutical generic products) cannot be so dissimilar as to completely alleviate the natural instinct to draw upon past knowledge to solve even new problems, leading to inadvertent adverse use if not disclosure. Here, where Amneal and Apotex share the same "API" (active pharmaceutical ingredient) (D. I. 131 at 108), and where the three cases initiated by Merck all involve "an anhydrate-based formulation [of mometasone furoate] that is bioequivalent to the brand" (id. at 108-109), the risk of inadvertent use should not be minimized. . . .

The crux of Dr. Cockcroft's testimony in the Delaware cases will be (as it was in New Jersey I): Did Dr. Cockcroft find monohydrate in the accused formulations? He did not in New Jersey I; we can assume that he will find it in the Delaware cases, albeit using different technology. . . .

Given the nature of patent litigation today (the "no stone left unturned" mentality), common sense also dictates that Apotex's competitors (Teva and Amneal) will attempt to use the discovery process at bar to impeach Dr. Cockcroft with his past work for Apotex, where his expertise was used to demonstrate non-infringement of the '353 patent. Indeed, Amneal has specifically indicated that it intends to seek "full discovery of all information relating to [Dr. Cockcroft's] prior testimony." (D.I. 131 at 109) As a point of fact, in response to requests for production of such information, Merck has explained that it "[could not] produce it because it contains Apotex's confidential information. . . ."

Of course, since Merck essentially "manufactured" the potential for a violation of confidentiality, by hiring Apotex's former expert, that cannot be a basis to resist lawful discovery motions -- or subsequent orders, in patent litigation. So Merck loses this one. And rightly so. Onward -- in a sweet hot wet rain here, now!

Opt-Out Plaintiffs In ENHANCE Federal Securities Suits Will Agree To An Immediate Certifying Appeal

Apparently agreeing that the issue I discussed at the end of last month is worth hearing from the Third Circuit on, prior even to Merck's having to answer the complaints, the plaintiffs have stipulated that the trial court ought to certify the potential time-bar question to the appellate court. [The graphic at right is from the settlement of the main federal securities class actions.]

So once again, the discovery/trial process for these opt-outs will be put on hold -- for perhaps eight months -- while this issue is briefed, argued and decided. We will likely have no news on the matter until next Spring, I'd guess. Here is the bit -- from Friday's filing:

. . . .On August 26, 2015, Your Honor entered Orders denying Defendants’ Motions to Dismiss on the ground that Plaintiffs’ claims under Sections 10(b), 20(a), and 20A of the Securities Exchange Act of 1934 were barred by the applicable five-year statutes of repose.

Defendants believe that this threshold timeliness question should be certified to the Court of Appeals because it presents a “controlling question of law as to which there is substantial ground for difference of opinion and that an immediate appeal from the order may materially advance the ultimate termination of the litigation.” 28 U.S.C. § 1292(b).

Enclosed for Your Honor’s consideration is a proposed Stipulated Order submitted on behalf of all parties that: (1) establishes a briefing schedule for a motion to this Court seeking certification of one or more controlling questions of law to the Third Circuit Court of Appeals pursuant to 28 U.S.C. § 1292(b); and (2) orders that Defendants need not file Answers to the Complaints pending resolution of the certification motion. If the Stipulated Order meets with Your Honor’s approval, we ask that it be entered.

We thank the Court for its consideration in this matter. . . .

Back to regular time, tomorrow -- and. . . Onward, one an all -- with a fine new week ahead!

Friday Afternoon Propecia® MDL Update: Order No. 3 Could Be Significant

First -- the caveats: I wasn't in the courtroom. And so, all I have to go on is this terse order. From the cold written record, there is no way to get the temperature of the judge.

Even so, were I representing Merck, I'd tread very lightly as to Number 3 below. If the judge were to decide that Merck had abused the privilege log process -- to hide discoverable documents -- and then in turn took the step listed. . . it would be unprecedented in major multinational pharmaceutical mass tort litigation in the US.

The order set forth in paragraph 3 is a clear shot across the bow type of warning. Merck's counsel would be wise to be be very sure every document claimed as privileged truly is. . . because the judge is likely to take another look. And if he found on second look that another sampled one-third or one-quarter were improperly withheld -- he'd almost certainly impose a harsh penalty on Merck. That penalty -- waiver of all privilege -- is something I cannot even imagine. It would be a nightmare for Kenilworth. So I expect far fewer shenanigans, going forward, here. From the order that resulted from the September 2, 2015 status call, then:

. . . .SCHEDULING AND RULINGS:

1. For reasons stated on the record the plaintiffs’ motion [Doc. No. 247] to compel the defendants to provide a Defendant’s Fact Sheet for all cases is denied.

2. For reasons stated on the record the plaintiffs’ motion [Doc. No. 248] and the defendants’ motion [Doc. No. 249] are both granted in part and denied in part. The parties are to confer and provide a Practice and Procedure Order that reflects the court’s rulings by September 11, 2015.

3. As discussed, the defendants will review the documents listed in their privilege log in light of the court’s order [Doc. No. 242] within 30 days to determine whether revisions should be made and documents produced. Following that review and further production, the plaintiffs may again raise concerns and, if necessary, move for a further review of documents by the court. The court advised that a further determination by the court that an excessive number of documents have been designated privileged could lead the court to make a finding that the defendants have forfeited the privilege and order complete production of documents itemized on the log.

4. The next status conference will be held on November 10, 2015 at 2:00 p.m. . . .

Safe travels -- one and all!

O/T -- An Elected Government Official Must Obey Governor's Lawful Orders -- And The US Supreme Court. Full Stop.

UPDATED: 09.04.2015 @ 2 PM EDT: As we indicated overnight, in comments -- per the Gray Lady's account:

". . .With clasped hands and tight smiles, James Yates, 41, and William Smith, 33, made their way through a dense thicket of reporters and photographers and stood before an employee of the clerk’s office to request a license — a routine clerical act turned into a national spectacle.

Mr. Smith said he and Mr. Yates, who live here in this small Appalachian city, had tried to obtain a license several times, but were denied each time. They spoke softly as they conducted their business with Deputy Clerk Brian Mason, their voices barely audible in the din. . . .

He and Mr. Yates could have gone to another county for a license, but "this is where we live," Mr. Smith said. "This is where we pay taxes. This is our home. . . ."

Love wins -- and the above makes it. . . obvious. Basic human dignity, now prevails. End updated portion.

I mention this largely in passing, since we have covered the emergence of the fundamental right of people to marry whomever they love, for some time here, now.

I must say that I think this Kentucky clerk has received extemely poor legal advice from Liberty Counsel. There is no plausible reading of the existing law that would allow an elected official to choose which laws she will obey, and which she will not. Here her choices are plain: issue marriage licenses to all (as she had previously sworn to so do), or resign her office. There is simply no fundamental right to "be an elected official" -- it is a privilege -- a privilege that remains contingent upon obeying the law of the land -- and discharging the lawful duties of office. Marriage equality is now clearly the law of the land.

I am genuinely sorry she is now in a federal jail-cell (likely believing, in error, that she is somehow being persecuted for her religious views) -- but it is largely the poor legal advice of Libery Counsel that has landed her there, in my opinion. Liberty ought to admit that no good faith extension of existing law would support the position they've backed her in taking.

Onward -- and I do trust now that love will prevail.

The Strange Tale Of Rolapitant -- Now To Compete With Merck -- A Legacy Schering-Plough Chemo- Nausea Med

While I don't expect this will matter much in any negative way to Merck, given its size, and long leading position -- with Emend^® in this US market space -- I do find these "Post-Script -- Epilogue" stories interesting, given that the narrative here directly involves the genesis of this blog. [My much earlier backgrounders -- here, and here.] It bears mentioning that the candidate did hit a few clinical trial bumps along the way -- as we might expect for any drug that Fred Hassan was seen touting.

I suppose one object lesson here is that a robustly active anti-trust/pro-competition FTC and/or DoJ in the US is a good thing. And -- though it took five or more years, we now have an on-market competitor, for this segment. [My experienced conjecture is that the rolapitant program would have been deep-sixed -- post the Schering-Merck deal in 2010 -- had the HSR antitrust review not required divestiture.] And that is good for patients, and payers. What a path this candidate had: from legacy S-P, to Opko, to Tesaro. . . now, to meet Merck (the old Schering-Plough entity, just renamed), head on, in late 2015. Here is FierceBiotech on the latest (an FDA thumbs up):

. . . .The FDA has given Tesaro a green light to start marketing rolapitant to help prevent some of the common side effects of chemotherapy. And now Tesaro will wage a David-vs.-Goliath battle for market share with a dominant Merck.

The Waltham, MA-based biotech had gone through an extended R&D journey before it hit the regulatory finish line with this drug, to be marketed as Varubi. The company in-licensed the drug from Opko back in 2010 for a small upfront, then ran into a bitter backlash from investors after the initial Phase III program failed to hit key secondary endpoints in late 2013.

A second Phase III that wrapped up last year, though, rang all the right clinical bells in preventing nausea and vomiting, setting up the regulatory package and today's approval. Analysts believe this drug could earn a few hundred million dollars a year. . . .

As I say, a few hundred million is peanuts to Kenilworth, but will nicely augement Tesaro's post IPO price and volume. Onward -- on a hot clear wonderful late summer afternoon -- with airport runs a'comin'!

Post Hoc Q: Did IMPROVE-IT Only Show Meaningful CV Benefits -- For Diabetics?

As ever, CardioBrief -- with Larry Husten on the keyboard -- does an excellent job of pointing out just how "fuzzy" the ultimate learnings may be -- from even large studies (with 18,000 patients) -- upon careful, closer (post hoc) data analysis.

In a sub-set post-hoc study, it would seem that the vast bulk of the CV outcomes benefit appeared in about only one quarter of the study's population: those who already had diabetes. Of course, correlation is not causation, and perhaps the diabetics were sicker, as a group, but it is. . . intriguing, nonetheless. Can we (as a finite resource/constrained payer-based system) justify these premium prices, for any non-diabetic cholesterol management patient in the US, where the outcome benefit seen in a very large group, over several years, was almost. . . non-existent? This is a very fair question -- and do go read it all, for some other competing theories to explain the subset data -- but here's a bit:

. . . .The beneficial effects of ezetimibe are found almost exclusively in patients with diabetes. . . .

The main IMPROVE-IT trial randomized 18,144 patients with acute coronary syndrome to the combination of ezetimibe and simvastatin or simvastatin alone. The primary endpoint of the trial– CV death, MI, documented unstable angina requiring rehospitalization, coronary revascularization after one month of treatment, or stroke– was significantly reduced in the ezetimibe group (32.7% vs. 34.7%, p = 0.016).

The ESC presentation focused on the 27% of patients in the trial (n= 4,933) who had diabetes. “We did see a quantitative, statistically significant interaction between diabetics and non diabetics,” said Giugliano. . . .

Giugliano concluded that diabetic patients were at higher risk than non-diabetic patients and that they had a greater relative and absolute benefit from the addition of ezetimibe. The greater benefit in diabetics was driven by reductions of MI and ischemic stroke. . . .

Almost a year ago, we had asked whether one fewer CV event, in 50 patients, over seven years, was worth almost an additional $750,000 in spending. [That's what the legacy Schering-Plough combo-pill Vytorin^® costs, compared to a generic statin.] I think the answer now will be. . . no, unless the patient is ALSO diabetic. Harlan Krumholz (the world renown expert, at Yale University) has all but said as much, previously. And so. . . onward. . . with a lovely end to a short week approaching. . . .