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

September 20, 2015 - Leave a Response

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. . .

September 19, 2015 - Leave a Response

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

September 18, 2015 - Leave a Response

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

September 17, 2015 - Leave a Response

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

September 16, 2015 - Leave a Response

We have long admired Dr. Califf (as the 2009-vintage graphic at right will attest). Overnight, our 44th 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

September 15, 2015 - Leave a Response

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 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

September 14, 2015 - Leave a Response

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 (

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.

Piper Jaffray Now Rates Merck At “Hold” — Target $60

September 14, 2015 - Leave a Response

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.

More Of the Back Story — On Merck’s Finasteride Franchise — And The Dominican Republic Connection

September 14, 2015 - Leave a Response

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® or, in some geographies, as Proscar®. 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.

On Propecia® MDL Observations — An Interesting Comment — And An Answer

September 11, 2015 - Leave a Response

This is from a fine comment below — 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.


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