Kenilworth Adds Genotype 4 To Its Combo Breakthrough Designation At FDA: Smallish Good News

April 8, 2015 - Leave a Response

UPDATED @ 2 PM EDT | Tracy Stanton at FiercePharma has some smart analysis of how, and when, all of this might play out. I still think Gilead is in the driver’s seat — and she does too. But do go read hers, here. [End, updated portion.]

Back in October 2013, Merck received an FDA breakthrough designation on the combo pill — for certain genotype 1 Hep C patients. That was withdrawn by FDA in January 2015, due to AbbVie’s (Abbott spinoff’s) success, out in the field. Today Merck reports that it has been re-granted that coveted status, related to a more narrow subclass — end-stage renal patients with genotype 1, as well as (for the newly added) genotype 4 patients — of all classes.

This is good news, and Merck is likely to present pretty strong (90% plus response rates) at the International Liver Congress meeting later this month. Here is a bit of The Wall Street Journal, on it all:

. . . .Merck said Wednesday that its hepatitis C drugs have been designated breakthrough therapies by the U.S. Food and Drug Administration.

The news comes three months after the agency said it would rescind breakthrough designation due to the introduction of competing treatments for the liver disease. The drugs, grazoprevir and elbasvir, cured at least 90% of infected patients in a mid-stage clinical trials and Merck is testing them in late-stage studies. It hopes to file an application to market a new two-drug, single-pill combination. . . .

We will — as ever — keep an eye on this, but with FDA having granted BMS’s Opdivo essentially a “next day” approval, after data submission on a breakthrough status, coupled to priority review — it seems there is a new order underway at FDA. So, it is not impossible that Merck might get a late June 2015 approval, after filing the data from the liver meeting, should it too win a priority review from FDA. We shall see.

Housekeeping Note: We will be off grid for the balance of the week, through to next Monday — unless something major breaks, inside Kenilworth. So, do be excellent to one another.

Yet Another New Round — In Merck v. Apotex Patent Wars — Over Nasonex®

April 7, 2015 - Leave a Response

Back in June of 2013, Apotex essentially won on appeal, as Merck was deemed not to have shown infringement in Apotex’s formulation of Mometasone Furoate Hydrate, branded by legacy Schering-Plough, now Merck — as Nasonex®. We covered that here, and here (in 2012), at the trial level as well.

It seems that Merck just filed a second piece of federal patent infringement litigation, in the federal District Court in Newark, NJ — primarily because Kenilworth suspects that Apotex is preparing to sell a modified version of its generic here in the States, now, upon FDA approval of its ANDA. The modification — Merck believes — could be either to the bottle shape, or the chemical construct. We will have to see. But here is a bit from the just-filed complaint (a longish PDF file):

. . . .On information and belief, the mometasone furoate nasal spray product sold in Canada is packaged in bottles that differ from the HW9234 samples previously provided to Merck in the Previous Litigation. For example, Apotex represented to the Court in the Previous Litigation that although changes had been made to the size, configuration, and composition of bottles for its mometasone furoate nasal spray product, those changes were made for submissions to the Canadian regulatory authorities only: “For Canada, [Apotex] also committed to submit data for JK7465 & JK7468, which contain 140 metered doses as [opposed] to 120 metered doses (for US). These batches also packaged with the new shorter bottle and pump with addilene change, but not with the nitrile change. . . .”

On information and belief, the generic mometasone furoate nasal spray offered for sale by Apotex in Australia contains the same formulation and is packaged in the same bottle as the generic mometasone furoate offered for sale by Apotex in Canada. Visual inspection of the bottles confirms that both contain 140 metered doses, are of the same size and shape, and share the same distinctive seam running down the side of the bottles. See, e.g., Exhibit 5 (photographs of Apotex’s Canadian product) and Exhibit 6 (photographs of Apotex’s Australian product). . . .

MRK-SGP-Q2-2013-Charge On information and belief, Apotex will conform its U.S. mometasone furoate nasal spray product to its offerings elsewhere in the world in an effort to leverage lower production costs and maintain profits while offering its product at a substantially reduced price. Therefore, Apotex will seek to manufacture, use, offer for sale, and/or sell a product different than that which was the subject of the Previous Litigation. . . .

We will keep an eye on this, even as Nasonex sales are eroding, quarter by quarter, here in the US. This is still a materially important brand, for Merck.

Arvinas’ Proteolysis-Targeting Chimera Tech Scores Big, With Multi-Phase Kenilworth Deal

April 7, 2015 - Leave a Response

This relationship could reach nearly a half-billion dollars in payments out of Kenilworth. Pretty strong validation of the approach, originally venture investment backed by 5AM Ventures, and Caanan Partners. More later — day gig calls. . .

A bit from FierceBioTech, and Damian Garde — do go read it all:

. . . .Under the deal, Merck will hand the New Haven, CT, biotech an up-front payment and research funding, promising more cash tied to development milestones and setting Arvinas’ maximum haul at $434 million if everything works out over the multiyear agreement. In exchange, Merck will get a chance to use the company’s proteolysis-targeting chimera, or PROTAC, technology, which creates small-molecule treatments that mark proteins for degradation. . . .

And so we shall, as ever, see. These two early stage investors stand to reap billions in returns, if the PROTAC can do in vivo, what it looks like it can do, in viro.

Congrats to Duke; condolences to the Badgers.

Kenilworth Slightly Adjusts Its Lobby Spend For Q4 2014 — Increases By $30,000

April 6, 2015 - 2 Responses

This is definitively immaterial, but I did say I’d note any changes. So here we go. . . .

Apparently Merck didn’t include some $30,000 of the Q4 2014 lobby-spend on its filing in January 2015. So now the figure is $490,000 spent internally, at Merck — not $460,000.

It would seem that nothing else has changed in the latest federal LD-2 form. The internal amounts were spent on:

. . . .340B (no specific bill), National Diabetes Clinical Care Commission Act (H.R. 1074, S.539), Eliminating Disparities in Diabetes Prevention Act (H.R. 3322), Oncology education (no specific bill), adult vaccine policies (no specific bill), medication adherence, DISARM (H.R. 4187), ACA Implementation (no specific bill), Hepatitis C education (no specific bill), HIV education (no specific bill), MODDERN Cures Act of 2013 (H.R. 3116), biosimilars (no specific bill), Alzheimer’s education (no specific bill)21st Century Cures (no specific bill), general pharmaceutical industry issues and education. . . .

Comprehensive tax reform (no specific bill), orphan drug tax credit (S.1128), R&D tax credit (no specific bill), base erosion (no specific bill), territorial tax system (no specific bill). . . .

Medicare Part D (general education, no specific bill), changes to low-income subsidy structure in Medicare Part D (general education, no specific bill), sustainable growth rate (general education, no specific bill), Medicare Part B (general education, no specific bill), Preserving the Integrity of Medicare Act (H.R. 5780). . . .

Intellectual property (general education, no specific bill), patent reform (general education, no specific bill); General budget issues (no specific bill), budget reconciliation (no specific bill); Education on beta-agonists (no specific bill), education on antibiotics and veterinary biologics (no specific bill). . . .

We expect to have “rolled up” — client wide — Q1 2015 figures in about a week, so check back here for those, then. Now you know. Onward, then.

Although Millennium Escaped This Integrilin® Suit, Schering-Plough (And Thus, Merck) Will Need To Develop Factual Defenses, To Escape

April 5, 2015 - Leave a Response

That said, I suspect that Merck — as successor to Schering-Plough — (in California’s federal Eastern District Court, before the very able Judge England) will eventually be able to show that the complaining party here, one Frank Solis, was not “the original source” of the allegations of kickbacks and overbilling, related to sales of Integrilin®, from 2002 to 2009. [Backgrounders here, and here.]

In order for the federal courts to have jurisdiction over these claims, the amended False Claims Act (circa 2006) requires that the complaining person be the original (non-public) source of the claims. So, even after Mr. Solis proves every word below is true, he will also have to establish that he was the original source of the proof/information. And it seems that most of these same sorts of allegations were made in an earlier-filed South Carolina state court proceeding against Schering-Plough, called Bentley. [Merck wasn’t a party in Bentley in South Carolina, because Merck did not yet own Schering-Plough, when the suit was brought (also circa 2006). But. . . this is how Millennium escaped this suit — by proving a prior public source, for the Solis allegations.] After some discovery, Merck may well be able to escape as well.

In any event, here is Merck’s latest filing (as a PDF file) as of this past Friday afternoon, asking for a reconsideration (essentially asking to be dismissed from the suit). And I’ll quote from the published opinion of Judge England (also a PDF file), denying that request:

. . . .[Schering-Plough salesman Frank Solis] describes, in detail, [Schering-Plough’s] alleged actions between 2002 and 2009 to convince physicians to write prescriptions of Integrilin for off-label uses. Those purported “kickback” activities included funding grants, paying excessive speaker fees, providing honoraria, furnishing meals, paying for attendance at Continuing Medical Education (“CME”) seminars while retaining control of virtually every aspect of the events so as justify off-label use and funding preceptorships and advisory boards. . . .

According to [Solis], [Schering-Plough’s] sales representatives were also instructed to send “invitations to lavish meals exclusively to targeted high volume prescribers or referral sources.” In light of all these activities, [Solis] alleges that the submissions of prescriptions for reimbursement were false because [Schering-Plough’s] illegal activities had influenced them. Again, while [Merck, Millennium and Schering-Plough] deny these allegations and claim [Solis] has shown no excessive remuneration that would run afoul of the [law], the facts. . . as alleged by [Solis] must be deemed true for purposes of ruling on a motion to dismiss. . . .

[Solis] need only show that [Schering-Plough’s] alleged illegal promotional activity was a “substantial factor” in the submitting of false claims. To state a viable False Claims Act case, [Solis] simply has to show that “one purpose” of the kickbacks is to induce prescriptions –- it need not be the only purpose of the kickbacks. U.S. v. McClatchey, 217 F.3d 823, 835 (10th Cir. 2000). . . .

So while it remains completely unclear whether Merck will ever get stuck with more damages, on Fred Hassan’s skunky, skanky bar bill here — since Mr. Solis may turn out not to be the original source of the allegations, it deserves mention that Mr. Solis has significant evidence that the complained-of conduct did in fact occur. Do be assured, this mess goes on Fast Fred’s bar tab — ultimately, in my book — as a matter of Karma, at least. But what do I know? — that’s just one guy’s opinion. Have a great week — coverage here will be spotty later in the week. Out of pocket and off the grid.

FINAL UPDATE: “WHO would Jesus. . . Hate?”

April 4, 2015 - Leave a Response

UPDATED 04.04.15 @ 10:15 AM EDT | I’ve decided to run this bit as a new post, given that it is — for Christians — Easter weekend, and as of this moment, according to their beliefs — their Redeemer has died a torturous death, and remains at the Gates of Hell (for devout Roman Catholics, in particular), at this moment. It is in this moment, the Vigil of Easter, that the true believers spend time reflecting on their own sins — their sins, which led their Redeemer to die on a cross, yesterday at 3 PM. It is at this Vigil morning moment, then that I ask those who claim this covenant to reflect upon their sins. I am no longer bound by that set of covenants, but I do still understand what Christians claim they mean.

So read on, you Indiana and Arkansas (and Georgia and Tennessee and North Carolina) “christians”. END UPDATED PORTION.]

I return to this topic to note how implausible it is, to me, that people of good conscience — truly devout religious people — if they were in fact the animating force behind these weaponized attempts to change existing law in Indiana and Arkansas — would come up with this particular scheme.

Most people of good conscience know that proving what lurks in one’s heart is a difficult endeavor. Most people of good conscience know, or know of, a story in which someone was likely treated unfairly (denied a job, promotion, seat at an elite institution, or other right or privilege of citizenship), and in many of these cases, there was a strong sense (unprovable, of course) that the denial was based on race, gender or other immutable characteristic. But proving what was in the actor’s heart — well that is nearly impossible.

And so, it is baffling to me — given that people of good conscience would not want anyone to be mistreated in this way — that they would ask for and in fact draft, a series of changes to a 1998-era federal law — to tip the balance in favor of the discriminatory actors. I do understand that it was a response to the fact that the Supremes struck Indiana’s attempt to amend its state constitution to prohibit gay marriage. That is a fact now beyond reasonable dispute. So, were these people acting in good faith, they might have appreciated how hard they were likely making it for a mixed race husband and wife, and their children to be vindicated, if (for example) the proprietor of a lunch-counter said his religion prohibited race mixing. And there are those out there. Yet these drafters left out any savings clause (akin to the one now being passed into Indiana law, as an amendment) that made clear that denials at any business establishment — on race or ethnicity or gender or LGBT status — would be strictly prohibited by law (as they have been for several decades, as to race, gender and religion, at least).

And so, Occam’s razor would suggest that there was only one goal, here — and that goal was to shift the burden of proof away from the person engaging in what would otherwise be unlawful conduct (invidious discrimination in public accommodations), and place that burden on the person whose status (LGBT) brought the invidious discrimination to the harsh light of 21st Century day. That is a very reasonable deduction, based on all that is now known. I would have expected better from supposedly religious people. And I would hope that Good Friday reminded them of some of this, yesterday.

Hint: I don’t think Jesus would have approved of the radical right’s recent actions, supposedly in His name, in Indiana and Arkansas. Here endeth the sermon.

Just A Few Clarifying Thoughts — On “Status” Compared To “Conduct” — Under US Constitutional Law

April 3, 2015 - Leave a Response

MRK-con-law-DWH-open-2015 Throughout my posts this week, I’ve highlighted what I see as the importance of being an open, welcoming force — in any debate that concerns public policy.

As I reflect on it though, I may have been too opaque in my use of legalese/shorthand. So here is a bit more, on what status vs. conduct implies (at least to my mind).

Throughout the evolution of our constitutional law, jurists have pointed out that choosing to act (or “conduct”, if you will) is very different than simply “being.” That is, being possessed of an immutable “status” (i.e., little or no conduct).

And so, historically, the choice — the “conduct” of refusing to serve someone, based on genuinely held religious beliefs, has been limited to churches, members of the clergy, and their closely affiliated not for profit counterparts. When the Supremes decided Hobby Lobby, they held for the first time that a for profit business, if closely held by people of strong, shared religious convictions, could refuse service, based on first amendment protected religious freedom. Whether I think that wise is immaterial. It is the state of the law, now.

On the other hand, the Supremes have long held that if one (even a devoutly religious one) chooses to avail oneself of the deepest capital markets on the planet, and the most robust free economy on the planet, and thus make often vast profits while doing so — the same free and open market rules must apply to all. That is, my status as LGBT cannot lawfully prevent me from being able to ask you to bake me a cake, if you want to sell your cakes to the public, and use jurisdictional means to do so.

And so, when you hear that these newly enlarged, “weaponized” RFRA laws, in Georgia, North Carolina, Indiana and Arkansas simply protect first amendment “free exercise of religion” rights, well that is. . . just false. [And it matters greatly that in many of the other states with older non-weaponized RFRA laws (like Illinois, for example), a pre-existing state wide law already protects LGBT status from being any lawful basis for discrimination.]

The weaponized versions attempt (unconstitutionally, I think) to place the first amendment “free exercise” rights above and over the fourteenth amendment’s promise of equality — and beyond the reach of the Commerce Clause, and all others. That is, the proponents of these laws believe that they should literally have their cake, and eat it to. They think that they are entitled to the free-est capital markets, and full participation therein — but also think they should not have to offer that full and free participation to people who. . . offend them, simply by choosing to love someone they don’t countenance — or in a way they don’t feel comfortable with.

So, as I’ve predicted, should any of these weaponized laws reach the Supremes un-amended, they will be stricken — on the grounds that for profit businesses open to the public must serve all members of the public — not just those whose status they prefer. Here endeth the sermon — but the trend is now away from the these wrong-headed weaponized RFRA bills.

So I ask you, dear readers, to think — should someone’s status be a reason — ever — to refuse them service, at a for profit public establishment? I think not. And I think the founders would have said the same. It is unfortunate that Justice Scalia thinks otherwise, in Hobby Lobby. But that too will evolve in time. . . . Onward.

Maybe Just “A Tempest In A Teapot,” But I’ll Note It — Zostavax® Edition (Per Cowen & Co.)

April 3, 2015 - One Response

First, the good news: Kenilworth has eclipsed the $750 million per year mark in sales of Zostvax®. That’s quite respectable, indeed. And to be fair, the Cowen analysis probably doesn’t play out in full until 2018 or later. But for its part, Cowen is pointing out that a GSK shingles vaccine candidate (called HZ/su) is preliminarily seeming to show better efficacy in people over the age of 60 — at preventing this condition (which disproportionately strikes the elderly). So, longer term, that might give GSK’s HZ/su candidate an important sales edge, in this, the most affected demographic. But that is quite a way from here — and a 16,000 person study needs to be completed by GSK. As a refresher, back in 2010, I detailed the challenges facing the Zostavax franchise, thus:

. . .On and off since 2009, there have been supply issues, due to difficulties in manufacturing these sorts of delicate biologics, at Merck. Next, and partially related to the first issue — until 30 minutes prior to administration, Zostavax must be kept hard-frozen (circa 16º — thus, there is no easy way to hold mass “point of common access” vaccine campaigns — at senior centers, for example — without heavy, high-end refrigeration equipment). In addition, insurers and Medicare require that separate forms be filled out for reimbursement — and that the patient pay out of pocket for it, before seeking later reimbursement through this arcane form submission process. On top of all that, though — the killer! — these shingles vaccines cost nearly ten times as much as the typical seasonal flu vaccine.

As the ACA of 2010 has become fully ensconced in the reimbursement world, though, the price compared to a flu vaccine has become less important. Most seniors (the target market in the US) now qualify for expanded reimbursement, under Obamacare. Which, in no small part, explains the $765 million a year in sales, in 2014.

But, just to complete the record — here is FierceVaccines, quoting Cowen, for your edification:

. . . .The incidence of shingles increases with age, but Zostavax’s ability to decrease risk of shingles declines in older people, the [Cowen & Co.] analysts wrote in a note. If Glaxo’s double-blind trial–involving 16,000 people in 18 countries–shows a more “robust” response in the elderly, it would be a key differentiator to Zostavax. . . .

We shall — as ever — see about that. In the meantime, we are shutting down early today, and planning to. . . overeat on Sunday. Smile. . . .

UPDATE: Indiana Takes At Least One Smallish Step — Away From The “Lunacy Precipice”

April 2, 2015 - Leave a Response

UPDATED 04.04.15 @ 9:30 AM EDT | I return to this topic to note how implausible it is, to me, that people of good conscience — truly devout religious people — if they were in fact the animating force behind these weaponized attempts to change existing law in Indiana and Arkansas — would come up with this particular scheme.

Most people of good conscience know that proving what lurks in one’s heart is a difficult endeavor. Most people of good conscience know, or know of, a story in which someone was likely treated unfairly (denied a job, promotion, seat at an elite institution, or other right or privilege of citizenship), and in many of these cases, there was a strong sense (unprovable, of course) that the denial was based on race, gender or other immutable characteristic. But proving what was in the actor’s heart — well that is nearly impossible.

And so, it is baffling to me — given that people of good conscience would not want anyone to be mistreated in this way — that they would ask for and in fact draft, a series of changes to a 1998-era federal law — to tip the balance in favor of the discriminatory actors. I do understand that it was a response to the fact that the Supremes struck Indiana’s attempt to amend its state constitution to prohibit gay marriage. That is a fact now beyond reasonable dispute. So, were these people acting in good faith, they might have appreciated how hard they were likely making it for a mixed race husband and wife, and their children to be vindicated, if (for example) the proprietor of a lunch-counter said his religion prohibited race mixing. And there are those out there. Yet these drafters left out any savings clause (akin to the one now being passed into Indiana law, as an amendment) that made clear that denials at any business establishment — on race or ethnicity or gender or LGBT status — would be strictly prohibited by law (as they have been for several decades, as to race, gender and religion, at least).

And so, Occam’s razor would suggest that there was only one goal, here — and that goal was to shift the burden of proof away from the person engaging in what would otherwise be unlawful conduct (invidious discrimination in public accommodations), and place that burden on the person whose status (LGBT) brought the invidious discrimination to the harsh light of 21st Century day. That is a very reasonable deduction, based on all that is now known. I would have expected better from supposedly religious people. And I would hope that Good Friday reminded them of some of this, yesterday. [END UPDATED PORTION.]

Indiana’s law — adopted just last Thursday — is today undergoing significant amendments — in the sausage-making that is the legislative process — as we type this.

That’s good — but is still well short of the mark. The offered “fix” covers only businesses — not human beings. So the fix will still leave individuals and small family run companies free to refuse service to LGBT paying customers, if these latter day luddites refusenik(s) (Ed. Note: Sorry — that insults the real refuseniks by association) offer a religious reason for doing so. Again, Indiana is a state without statewide fourteenth amendment-, and federal EEO-“style” acknowledgements (i.e., a firmly rooted protective scheme) for LGBT Hoosiers. The same is true of Arkansas, but it too is moving in the right direction, now — as I noted yesterday. Here is just a bit from CNN:

. . . .The changes would prohibit businesses from using [last week’s enacted Indiana version of RFRA] as a defense in court for refusing “to offer or provide services, facilities, use of public accommodations, goods, employment, or housing” to any customers based on “race, color, religion, ancestry, age, national origin, disability, sex, sexual orientation, gender identity, or United States military service.” . . .

As CNN notes, though, the Indiana government machinery is almost certain to face debate on a full anti-discrimination and equal treatment measure, very shortly. So, sometimes — “when she pushes too hard, she gets exactly the opposite of what it was she wanted, in the first place. . . .” it has been ever thus.

“Epic Fail” RFRA Update: Arkansas Purports To Rewrite 75 Years Of Federal Constitutional Law With A Pen Stroke — Yes. Epic Fail.

April 1, 2015 - Leave a Response

UPDATED 04.01.15 @ Noon EDT | Sanity makes a comeback, in Arkansas, per the Gray Lady — just now:

. . .Gov. Asa Hutchinson of Arkansas on Wednesday called on the state lawmakers to recall or amend legislation billed as a religious freedom measure to make it mirror a federal version passed in 1993.

Mr. Hutchinson, a Republican, said he understood how divided the state and the country was over same-sex marriage and religious freedom — his own son, Seth, had asked him to veto the bill, which critics say could allow individuals and businesses to discriminate against gay men and lesbians.

He said he was also considering using an executive order that would make “Arkansas a place of tolerance. . . .”

This is overdue — but good news, just the same. Now — where is the Indiana repeal/amendment?

[END, UPDATED PORTION.]

I cannot sit silently here, any longer. Arkansas is preparing to sign into law a measure similar to Indiana’s wrong headed, hateful nonsense — but with yet another notable enlargement. [Background on the Indiana law here.]

Arkansas proposes to require, in addition to all the things the Indiana law purports to require, that if a business claims a religious reason for refusal of service, the state (or the person refused service) would have to show that the civil rights measure not only served a compelling state interest, by the least restrictive means, BUT ALSO that that civil rights measure is “essential” to the executive power of preserving ordered liberty, in Arkansas.

As is true with Indiana’s law, this one will ultimately be struck down by the United States Supreme Court. For 75 years the federal Constitution has been read to prevent invidious discrimination based on immutable status — not conduct. As I said Monday, these laws would purport to shift the burden to the person whose civil rights have been abridged — to prove that the request for service was the least restrictive means of asserting a civil right, and furthered an essential, compelling police power interest inside the state. The federal Constitution countenances no such right on the part of the states, jointly or severally — and it certainly doesn’t allow people who hold their for profit businesses open to the public — and accept all the benefits of the greatest capital markets on the planet — along with all this freedom to transact, to then deny that same freedom to others.

Here is a bit of the latest, from a fine New York Times rundown, overnight:

. . . .Both states’ laws allow for larger corporations, if they are substantially owned by members with strong religious convictions, to claim that a ruling or mandate violates their religious faith, something reserved for individuals or family businesses in other versions of the law. Both allow religious parties to go to court to head off a “likely” state action that they fear will impinge on their beliefs, even if it has not yet happened.

The Arkansas act contains another difference in wording, several legal experts said, that could make it harder for the government to override a claim of religious exemption. The state, according to the Arkansas bill, must show that a law or requirement that someone is challenging is “essential” to the furtherance of a compelling governmental interest, a word that is absent from the federal law and those in other states, including Indiana. . . .

Insanity. And so, I will leave you with a video — to describe the metaphor this current struggle most closely resembles:

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