Wednesday, April 1, 2015

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


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:



Tuesday, March 31, 2015

BMS's Opdivo® Is Still In Front, But This Is Keytruda® Good News


Merck today announced that it will conduct more Phase 1b (i.e., early) studies with another oncology agent in development at Syndax. Financial terms were not disclosed, but this is a nice validation for Arlene Morris, the CEO of Syndax. She continues to embellish her "street cred" here. And Merck can certainly use the help, too. BMS is the one to catch (nivolumab, branded as Opdivo®), in this space -- as I've said for well over 18 months.

From Xconomy Boston, this morning -- a bit (do go read it all):

. . . .Syndax Pharmaceuticals sidestepped an IPO a few months back when it found its cancer drug, entinostat, might have a benefit it didn’t originally anticipate. Now the Waltham, MA-based company is putting that thesis to the test through a deal with Merck.

The two companies announced this morning that they’ll run a Phase 1b/2 clinical trial testing Syndax’s entinostat with Merck’s so-called “checkpoint inhibitor” cancer drug, pembrolizumab (Keytruda), in patients with either advanced non-small cell lung cancer or melanoma. Financial terms weren’t disclosed, but Merck and Syndax will start enrolling patients in the second half of the year. They could also exercise an option to extend the pact to a Phase 3 study if all goes well. . . .

Syndax. . . won a breakthrough therapy designation from the FDA for entinostat in breast cancer — but another opportunity unexpectedly opened up too. A preclinical study published in the Proceedings of the National Academy of Sciences last year showed that entinostat might boost the effectiveness of two types of checkpoint drugs—PD-1 and CTLA-4 blockers, which help the immune system recognize tumors. PD-1 inhibitors (like Merck’s pembrolizumab) and CTLA-4 blockers (such as Bristol-Myers Squibb’s ipilimumab (Yervoy)) are among the first in a new wave of cancer treatments that harness the immune system, rather than just nuke tumors and healthy tissue like chemotherapy. . . .


So -- as ever, we shall see. But a Phase 3 study is a good $100 million to $250 million away from today's spend. Still it is good news. Onward, to tomorrow, one and all. [And just for fun, given yesterday's post -- I am certain that the Governor of Indiana will be true to his word, and let these churches of cannabis worship without interference. Aren't you equally sure of it? Irony. That's for me -- irony!]

Monday, March 30, 2015

This Blog Is Open. . . For Everyone!


This past Thursday, the legislature passed, and Indiana's Republican Governor Pence signed into law, what it calls a Religious Freedoms Restoration Act (RFRA). The Indiana version contains several notable changes from the model one that ultra-conservative Republicans have been pushing in statehouses around the nation. [For its part, Colorado killed the version introduced there. I am certain that the Governor of Indiana will be true to his word, and let these churches of cannabis worship without interference. Aren't you equally sure of it? Irony. That's for me -- irony!]

Back to the main story -- the Indiana version grants parties the right to bring legal action to prevent a “likely” burden on religious belief, even before any burden is imposed. And it expands the situations in which the protection could be invoked to include disputes between private parties engaged in lawsuits, even if they do not involve any direct actions by a government agency. These are extremely weighty modifications, and turn what was a shield into a sword.

Arkansas has a version pending on its Governor's desk. Ugh.

Let's start with the basics: these laws are entirely unneeded. The first amendment allows any business to claim a religious purpose for any given act. But current law fixes the burden of proof on the person claiming the first amendment right (generally speaking). It should take a very muscular, particularized and precise argument to make a first amendment claim in a way that would allow a business open to the public. . . to refuse service to any person, based on status rather than conduct.

Indiana's version of the RFRA (and the one pending in Arkansas) both purport to SHIFT that burden -- make the burden belong to the state (or the complaining person, the one refused service), to prove that ALL laws -- not just ones on service -- are the least restrictive means of achieving a compelling state interest. So, the Indiana law gives the business a clear advantage in any lawsuit based on a refusal to serve any person (based on status). It shifts the burden, and presumes that the business was exercising a religious view. Even if the business were so exercising -- the federal fourteenth amendment can be read to say that if one holds oneself open for commerce with the public, and uses jurisdictional means (advertising, telephone, computers connected to the web, etc.), then denial of service based on status is going to be a highly suspect and likely invidious state of affairs. In short, quite rightly, most times the person(s) refused service will prevail, if they can afford to press the matter in court. [So, a decade from now, the Supremes will likely strike the Indiana version of the RFRA as repugnant to our federal Constitution. But we should not have to wait that long for justice and equality, in my view.] Let's follow along here, then. . .

Now imagine the same facts under the Indiana RFRA -- and the person(s) denied service likely loses, because all the business need say is that it had a religious objection, and posted a sign to warn the public -- and that would be enough, to escape a lawsuit, intact. I frankly would not to live in such a state. I will not spend my money in that state, either. I agree with Tim Cook, of Apple.

Here in Illinois, and in Colorado, California, Nevada, New Mexico, much of the Northwest, and almost all of the Northeast (map here) there are state-wide bans on such discrimination. Not so, in Indiana, Tennessee and Arkansas (among others -- they are in gray, on that ACLU map). Disgusting.

Even so, the fact that Indiana doesn't have a state-wide ban on discrimination against LBGT people, may only lead to MORE litigation proliferation there, as the federal constitution can likely be read to imply a right to equal treatment, where and when the basis for purported discrimination is driven by status, not conduct.

I am deeply frustrated that Governor Pence is pretending not to understand how important shifting the burden of proof here is. So -- this blog and business and site -- like Merck itself -- is open for everyone! [Feel free to download, and use the lower left image -- to join the campaign, on your site.]

UPDATED: 03.30.15 @ 11:15 AM EDT | Despite repeatedly dodging direct questions on these matters on Sunday morning national TV news programs yesterday, Governor Pence is now "open" to amendments and clarifications being drafted by the two top legislators in the Hoosier state.

With the travel and trade of the NCAA Final Four hanging in the balance over the coming weekend there, as well as pressure from the NBA, Apple and Angie's List -- he ought to rethink that earlier bone-headed stance. In any state where a state-wide prohibition on discrimination based on sexual orientation and gender identity does not yet exist, a bill like the RFRA would create significant havoc. Just like the Boycott Arizona move of a few years back -- on "show us your papers" -- I think the threat of loss of commerce is the best way to end this nonsense. Onward.


Sunday, March 29, 2015

Gilead Vs. Merck: Despite Raging Discovery Battles In California's Northern US District Court, I STILL Expect This Will Settle Via ADR


As of the end of this week, there is a motion to compel pending, against Merck -- and it offers some rather pungent assessments of what nearly sounds like an allegation of bad faith, on Kenilworth's part -- according to Gilead's lawyers.

Meanwhile, globally the Gilead v. Merck/Idenix/Isis sofosbuvir patent spats march forward on at least seven fronts. The stakes are gargantuan (perhaps more than $10 billion in damages is at stake), but the lawyers' bills must now be running over $75 million per year, world-wide, if we add up both sides' legal expenses. And that, my friends just doesn't make sense, for the shareholders of either company.

Remember, if there isn't a settlement or other resolution before December 14, 2015 -- a little under a nine months from now -- the very able federal District Court Magistrate Judge Christopher J. Burke, sitting in Wilmington, Delaware, has ordered the beginning of an ADR processes. [Prior rundown of the international litigation status here.]

Each side knows that it ought to find a solution both can live with, by agreement, prior to then, or they will run the risk that a panel of arbitrators, or a mediator, will impose one upon them. This is, in my estimation, a smoke signal from the court that it feels the case ought to be settled -- and settled soon. Here's a bit of that order, entered on New Year's Eve 2014:

. . . .IT IS ORDERED that a teleconference has been scheduled for Monday, December 14, 2015, at 11:00 a.m. with Magistrate Judge Burke to discuss alternative dispute resolutions. . . .


I would hope that, come December 2015, the central point of discussion will be whether Gilead might be willing to pay perhaps one half of one per cent in royalties to Merck -- to "buy peace". That would be a 20 fold discount (or a 95 per cent decrease, if you prefer), from Merck's initial 10 per cent of all sales demand. As I've written before, if it settles prior to December 2015, my guess is that it will settle at a rate below 1.5 per cent of sales. And that would not even be a $200 million settlement. At $75 million a year in legal expenses, it sure makes sense to get this over with, capping it at $200 million. Just my musings, here.

Now when the Sun inexorably rises, I'll be off for the northlands -- (do enjoy Mass) on a fine Sunday morning, here. Be kind to one another. For in the end, only kindness matters.

Saturday, March 28, 2015

Second Imposition Of Three Day "Stay At Home" Orders Underway In Sierra Leone, Tonight


We here in our lil' shop continue to search the newswires diligently, for any signs of good news on the current and unspeakably tragic Ebola outbreak. Along those lines, we do know that the Phase II trials in Guinea have moved into Phase III -- that is, the scientific consensus now holds that the vaccine candidates are completely safe. And so, the studies will henceforth focus on durability of the immune responses, going forward.

Against the backdrop of that rather hopeful news, we learn that Sierra Leone has imposed (for a second time) a three day ban on unneeded movement, for all her 6 million citizens. The idea is to avoid complacency -- and continue to focus awareness on safe practices. Difficult times. . . require difficult measures. Here is the "Beeb" (BBC) on it all:

. . . .This lockdown comes amidst some rare good news. According to official figures from the World Health Organization, there were just 33 new confirmed cases last week - the lowest number since June 2014.

But with these falling figures there is danger of growing complacency, the government says.

This is one of the main reasons behind the lockdown - volunteers will remind people how to protect themselves against a virus that is still a real threat.

They will focus their efforts on northern and western areas where some infections still come as a surprise to officials - 16% of cases last week were not known Ebola contacts.

Experts have criticized previous stay-at-homes as too heavy-handed and top-down in their approach. Concerns were raised that some people did not have access to food.

The hope is, a year after the outbreak was declared, such logistical problems have been ironed out and that this measure will bring the country closer to its goal of zero Ebola infections by April 15, 2015 - an ambitious target that is just two weeks away. . . .


Sleep tight, one and all. And if you are so inclined, do ask the Infinite for some support here (I myself am bound by a differing covenant). Yes, tomorrow is another day.

Friday, March 27, 2015

Merck Q1 Results: April 28, 2015 -- Before NYSE Opens


We will tune in on that morning.

. . . .Merck will hold its first-quarter 2015 sales and earnings conference call with institutional investors and analysts at 8:00 a.m. EDT on Tuesday, April 28. During the call, company executives will provide an overview of Merck’s performance for the quarter.

Investors, journalists and the general public may access a live audio webcast of the call on Merck’s website at merck.com. A replay of the webcast will be available at approximately 11:00 a.m. EDT on April 28 and will remain on the website for 12 months. The sales and earnings news release and supplemental financial disclosures also will be available in the Newsroom and Investor sections of the company’s website. . . .


Have a great weekend, one and all!

Wednesday, March 25, 2015

UPDATE: At Least Until April 28, 2015, Glenmark May Continue To Manufacture And Sell Generic Sitagliptin In India -- Supreme Court Of India


In an update to our coverage of last week, the Indian news-wires are reporting this morning that the Supreme Court of India has granted Glenmark a stay on the injunction -- through April 28, 2015 -- when their Supremes will hear the Glenmark appeal. That means Glenmark is free to keep selling its "at risk" generic sitagliptin in India (a right the High Court allowed, in any event, to sell off Glenmark's existing inventory).

I am uncertain about this, but it would surprise me if Glenmark didn't already have enough inventory on hand to keep shipping through April 28, 2015. In the event that it does not, it is now free to manufacture enough to reach that date. Glenmark may still have to pay Merck a royalty on all these sales, but the people of India may still source cheaper generics from Glenmark. Here's a bit, locally:

. . . .Supreme Court today stayed util April 28 the order of Delhi High Court barring Indian pharma major Glenmark Pharamceuticals from making, marketing or selling its anti-diabetes medicines in which US drug major Merck Sharp and Dohme (MSD) has claimed patent right.

"Up to April 28, there will be an interim stay on the order of the High Court," a bench comprising Justices Ranjan Gogoi and N V Ramana said. . . .


So, even if the Indian Supreme Court decides that the High Court's injunction will stand -- Glenmark will likely only ever owe Merck a running royalty on sales -- through the date of that decision. I do think the Supremes will ultimately enjoin Glenmark, and effectively force it to buy a license from Kenilworth, but I expect that generic sitagliptin therapies, from either "authorized generic" sources -- or Glenmark and Aprica -- i.e., non-authorized sources. . . are here to stay, in India. Merck has tacitly acknowledged this fact, by reducing its own pricing in country, since 2014.

Tuesday, March 24, 2015

Merck Replenishes Stock Repurchase Program -- Incremental $10 Billion Equal To May 2013 Authority


Just as it did in May of 2013, Merck has once again added an incremental $10 billion of stock buyback authority, tonight, after the NYSE closed for the day.

A more jaundiced viewer might ask whether Kenilworth cannot find some higher -- internal rate of return on capital hurdle exceeding -- use for that $10 billion of capital, now deployed to the pockets of shareholders wishing to get liquid. Afterall, "investing" in a buyback just exactly meets one's cost of internal equity capital. True enough -- it won't drag the return rate down -- but it doesn't bump it up, either.

And that is a fair view. Moreover, shareholders don't mind the soft support a buyback program of size offers, should there be an anomalous dip in the NYSE price, on a temporary basis. Then the stock repurchase program can kick in -- and act as gentle slow support to the price.

I do wonder though whether Merck might see a higher return on that capital, longer term, by investing more in a Keytruda trial/launch in yet another cancer. Here's a bit, from PharmiWeb simply parroting the presser from Kenilworth:

. . . .With today’s announcement the company’s total outstanding share repurchase authorization is now approximately $11.7 billion which includes approximately $1.7 billion in authorized repurchases remaining under the program previously announced on May 1 2013.

Merck continues to expect average diluted shares outstanding will be approximately 2.86 billion in 2015. . . .


So -- I'd look for a mild price rise, in the coming weeks -- or at least less erosion than the general DJIA experiences, due in no small part to the cushion of a replenished $10 billion repurchase program.

Doctors Without Borders Report: Last Week, The Ebola Outbreak Turned One. . .


However. . . rather than dwell on all the quite accurately-reported problems with the global response to this outbreak, from Doctors Without Borders, I'll choose to highlight two old, but promising, antiviral agents that seemed to work, in at least a few post contraction human cases, to arrest progression of the hemorrhagic virus. [See graphic at right, and the European Community statements here.]

I suppose the enduring tragedy of it all will turn out to be that there was no need for the outbreak to see its first birthday. Had we, collectively, made finishing this vaccine candidate (long ago discovered in Canada) a priority, the outbreak may well have ended in just a few months -- and not have claimed upwards of 11,000 lives. In any event, here is a bit from Wired, this morning:

. . . .Last week, the Ebola epidemic in West Africa achieved its first birthday. Though the viral outbreak has been contained, it is still not under control: According to the World Health Organization, cases continue in Sierra Leone and are rising again in Guinea. Liberia was about to record an entire incubation period without a new case — a signal that the chain of person-to-person transmission might have been broken — but on Friday, it announced that it had found a single new case. How that woman became infected is unclear; it is possible that she represents, not a new outbreak, but a brief interruption in an otherwise promising trend.

It has been decades since there was an epidemic of this persistence and magnitude. No other Ebola outbreak matches it; nor does the 2003 epidemic of SARS. You would have to go back to the early days of HIV in the 1980s, or to the flu pandemics in 1968, 1957 or even 1918, to find an outbreak that sickened so many people, challenged international response capacity so much, and instilled such fear in other countries. . . .


Even so, with at least two vaccine candidates showing promise, and these antiviral agents, we may be just a few steps away from turning the corner, here. Onward.

Good News -- But Unsurprising -- Pembrolizumab (Keytruda®) Is An Effective First Line -- In Melanoma


I'll highlight it here, because it adds to the thesis: Anti PD-1 immuno approaches are the wave of the future -- in many, many cancers.

Good news, for Kenilworth, and cancer patients. The high burden disease states await. Here's the Merck presser:

. . . .[Merck] today announced that the randomized, pivotal Phase 3 study (KEYNOTE-006) investigating Keytruda® (pembrolizumab) compared to ipilimumab in the first-line treatment of patients with advanced melanoma has met its two primary endpoints of progression-free survival and overall survival. The trial will be stopped early based on the recommendation of the study’s independent Data Monitoring Committee. . . .


Enjoy a productive Tuesday now, one and all.

Saturday, March 21, 2015

Some Sad News Concerning Liberia; Even As "Ring" Ebola Vaccine Candidate Trials Continue for Merck, In Guinea


As is so often true, out in the wild, biological life forms just. . . find a way. They adapt. They evolve. Just as we all inexorably do. But we will certainly hope that these viral agents do not mutate -- not too quickly, nor too radically, this time around.

This is all a stark reminder that all science is only as good as the biology that supports it. I suppose I should, on a positive note, remark that in Guinea the large scale "ring" trials of Merck and NewLink, as well as those of GSK, continue to enroll robustly (due in no small part to a series of payments, roughly equal to ten-weeks' full-time wages, to recruit volunteers in-country). It would be reassuring to know that we -- as a planet -- have a safe, effective vaccine or two in hand, as these outbreaks reappear. [And if history has taught us anything, it is that they will reappear.]

But for now, we will worry that it evolves or mutates before it can be tamped down. Here is the latest bit, out of Monrovia (Liberia's capital city), from DM Akadamie -- do go read it all:

. . . .Officials in Liberia were scheduled to meet in an emergency session on Saturday in the latest chapter of the Ebola epidemic.

The cause of the meeting was announced the evening before when health officials confirmed that a woman in the capital city Monrovia had been diagnosed with the hemorrhagic virus.

"This is a new case after we have gone more than 27 days without a single case. It is a setback," government spokesman Lewis Brown said.

The last confirmed Ebola patient in Liberia was discharged from hospital on March 5, prompting a 42-day countdown to begin until the West African country could be declared free of the fatal disease.

Since the outbreak of the epidemic in December 2013, the United Nations has counted over 10,000 Ebola-related deaths, nearly all of which occurred in across Liberia, Guinea and Sierra Leone. Health officials, while hopeful that Liberia would report no new cases by mid-April, remained aware of the threat posed by the neighboring West African nations still crisis-ridden. . . .


With this bit of disheartening news, we will look forward to a quiet and reflective Sunday, here. So it goes.

Friday, March 20, 2015

Januvia® Patent Litigation In India Continues -- Over "At Risk Launched" Generic Sitagliptin (-Phosphate) -- But Merck Wins A Round


We've been waiting for a little over 21 months for clarity on this request for an injunction by MSD India, the local Merck & Co. affiliate there.

This very morning, as various and sundry Indian news outlets are reporting -- the Delhi High Court three-judge panel has granted Merck an injunction, keeping any new inventory of the Glenmark generic form of sitagliptin off market there. However, Glenmark will be allowed to sell out its existing inventory of Zita and Zita-met, the knockoffs of Januvia®, and Janumet®.

As we first reported in June of 2013, MSD India was granted a similar order, barring another generic maker -- Aprica -- from selling a generic form of sitiagliptin phosphate in India.

. . . .The Delhi high court on Friday restrained Indian firm Glenmark Pharmaceuticals from manufacturing, marketing or selling its anti-diabetes drugs Zita and Zita-Met, saying it has “prima facie” infringed the patent of US drug major Merck Sharp and Dohme (MSD). . . .

The court also set aside its single-judge’s 5 April 2013 order refusing to restrain Indian company from manufacturing and selling its medicines meant for treatment of Type-2 diabetes. . . .

The bench, however, on Glenmark’s oral plea to allow it to sell its goods already in the market, clarified that it “may sell such of the products which are already in the market i.e in possession of its distributors and retailers”. . . .


I still think there will be a global settlement here, with all the generic makers -- since diabetes represents such a high-burden disease in the relatively limited means populations of India. But we will keep you apprised.

For now, Merck has been able to take another extremely low price alternative off-market in India. Even so, Merck sells its own branded sitagliptin (Januvia) at a big discount in India, compared to what it charges in the US, and EU. On a global basis, the company's sitagliptin sales growth (in dollars) has slowed for Kenilworth, since mid to late 2014, in part due to these factors we have been steadily covering. Now you know. [NB: Weekend outage alert -- traveling and out of pocket.]

Wednesday, March 18, 2015

Merck Shares Rise 2 Per Cent -- After Announcing "Late-Breaking" NSCLC Keytruda® Data Presentation: Mid April 2015


While we don't yet know how the data reads out, we may infer fairly safely that it will put Kenilworth in the hunt for an NSCLC FDA label expansion/approval -- on Keytruda® -- in late 2015 or early 2016. And that is a good thing, given the immense burden that lung cancer represents -- as a disease state.
Expect more later, as I am road-blogging here. Here is a bit from the press release, out of Kenilworth at around 4 PM EDT today:

. . . .The NSCLC data will be the first presentation of new efficacy and safety findings for KEYTRUDA from 495 patients, including validation of PD-L1 expression (abstract #CT104). These data are from the largest, multi-center Phase 1b (KEYNOTE-001) study of an anti-PD-1 therapy. With the mesothelioma findings (abstract #CT103), data evaluating KEYTRUDA will have been presented in eight different types of cancer. . . .

Graphics will follow. Even if the NSCLC data doesn't allow for/get granted a priority review at FDA, this is materially good news. Maybe Merck is now only six to nine months behind BMS -- maybe. Not nine to twelve. And maybe a little under six, if FDA grants Merck a priority review designation. We shall see.

Monday, March 16, 2015

WHY Leerink Swann Reduced Its Merck Target To $62.50, From $66 -- Fernandez's Latest Opdivo® Analysis


In a word -- BMS's Opdivo®.

It seems Seamus Fernadez agrees with us: Merck's Keytruda® fortunes are at least marginally worse (albeit in a slightly material fashion), post the news of eleven days ago. Here is a bit, from the Leerink key take-aways, at that firm's 2015 conference on global healthcare. Do go read it all:

. . . .Off-label reimbursement [for BMS's Opdivo] has been challenging to date, but the KOL believes that lung cancer approval in one setting paired with the available scientific publications and abstracts should drive reimbursement across multiple lines of therapy or histologies. Both physicians believe that 2nd line approval of PD1/ PDL1 could change the progression from 1st to 2nd line therapy such that the discontinuation rate between 1st and 2nd line treatment could be much less than the frequently cited 50%.

In addition, it was suggested that savvy physicians could employ a “fast-fail” strategy with chemotherapy in order to more quickly start patients on these life-saving drugs. One KOL noted a similar strategy with Zytiga (abiraterone) which broadened use earlier than most expected. . . .

Opdivo [is] expected to quickly replace Afinitor in 2nd line kidney cancer; assumes success of BMY’s -025 study. The genitourinary specialist (prostate, kidney) was confident that BMY’s Opdivo would best Afinitor in the head-to-head 025 study largely because Afinitor is such a poor treatment standard. He predicted that once available, Opdivo will quickly replace 100% of Afinitor use in kidney cancer. He noted, however, the need for combination therapy to demonstrate improved overall survival vs. 1st line VEGF TKIs.. . .


Sleep well, now one and all!

Sunday, March 15, 2015

The Week That Was: Jefferies Still See-Sawing On Merck


I suspect this slight down-beat was due to BMS's Opdivo® receiving an FDA lung cancer (NSCLC) nod, during the past ten days. It marginally erodes Merck's market cap potential. But only marginally.

Jefferies' Seamus Fernandez is unlikely to alter his views very much on Merck, or BMS (or J&J, for that matter) in the near term. He has bounced it around, quite a bit, from $65 to $60 -- with one stop north of there, only -- in the last 24 months. Here's a bit, from a reprint of an earlier time:

. . . .Jefferies Group has also taken action a number of other healthcare stocks recently. The firm lowered its price target on shares of Merck & Co., Inc. from $63.00 to $62.00. They have a hold rating on that stock. Also, Jefferies Group raised its price target on shares of Johnson & Johnson from $108.00 to $110.00. They have a hold rating on that stock. . . .


So -- really no news at all. And so, we waited until Sunday morning to note it, casually, over coffee, juice and a banana.

Saturday, March 14, 2015

O/T, But Only Once A Century -- Epic Pi Day 3.141592653!


Well, I suppose it belongs here -- because of its importance to all of the life sciences, generally. And -- as someone I love told me yesterday -- I'm a goof for it. True -- but my adoration of it is. . . shameless.

From The New York Times opinion page, this afternoon, then:

. . . .Early mathematicians realized pi’s usefulness in calculating areas, which is why they spent so much effort trying to dig its digits out. Archimedes used 96-sided polygons to painstakingly approximate the circle and showed that pi lay between 223/71 and 22/7. By the time Madhava (in India, around 1400) calculated pi to over 10 decimal places using his groundbreaking infinite series (which regrettably bears Leibniz’s name), it was already more than accurate enough to address all practical applications. Pursuing pi further had essentially become a mathematical challenge. . . .


I just had a big slice of warm pecan pie, literally swimming in dollops of whipped cream. . . so my celebration and observance is. . . complete! Have you. . . had yours?

Friday, March 13, 2015

I Hate Being Right About This Kind Of Stuff: Bridion® -- No St. Paddy's Gift -- At FDA



Buried on a Friday afternoon before St. Patrick's. . . .

I'll have more in a few minutes, but this former Fast Fred "Star" just cannot catch a break. The review at an Advisory Committee of FDA next week was just. . . scrubbed. Pulled. Dumped. From Kenilworth's presser, then:

. . .The FDA has advised Merck that it plans to conduct additional site inspections related to a hypersensitivity study (Protocol 101). The Agency has indicated it plans to conduct these additional inspections prior to an Advisory Committee meeting and completion of their review. Due to the timing of the additional inspections, Merck expects to receive a Complete Response Letter at the time of the Prescription Drug User Fee Act action date for the NDA for sugammadex on April 22, 2015. Merck will continue to work with the FDA as it completes its review. . . .


Alas -- no luck of the Irish there. We had mentioned this scheduled FDA Advisory Committee meeting at the beginning of the month. Oh well. What a tortured path this operating suite drug candidate has endured -- largely due to legacy Schering mismanagement of the studies, and miscalculations in the FDA filing strategy, in that legacy law department. So it goes. Maybe 2016 will be its year. It feels a lil' like my. . . Cubs. Smile.

Thursday, March 12, 2015

Well -- Apple Moves At Lightning Speed, It Seems: UPDATED "Informed Consent" Guidelines For Stanford Med App


Barely eight hours ago, we wrote about the "brave new world" of clinical trial recruiting. . . via an ingeniously simple and elegant iPhone App -- released just Monday. Tonight, AppleInsider is reporting that Apple has already tightened its developer guidelines to address the patient confidentiality and informed consent concerns that FDA and other regulators around the globe might justifiably articulate.

From those just-revised Apple Developer Guidelines, then:

. . .27. HealthKit and Human Subject Research

27.1 Apps using the HealthKit framework or conducting human subject research for health purposes, such as through the use of ResearchKit, must comply with applicable law for each Territory in which the App is made available, as well as Sections 3.3.28 and 3.3.39 of the iOS Developer Program License Agreement

27.2 Apps that write false or inaccurate data into HealthKit will be rejected

27.3 Apps using the HealthKit framework that store users’ health information in iCloud will be rejected

27.4 Apps may not use or disclose to third parties user data gathered from the HealthKit API or from health-related human subject research for advertising or other use-based data mining purposes other than improving health, or for the purpose of health research

27.5 Apps that share user data acquired via the HealthKit API with third parties without user consent will be rejected

27.6 Apps using the HealthKit framework must indicate integration with the Health app in their marketing text and must clearly identify the HealthKit functionality in the app’s user interface

27.7 Apps using the HealthKit framework or conducting human subject research must provide a privacy policy or they will be rejected

27.8 Apps that provide diagnoses, treatment advice, or control hardware designed to diagnose or treat medical conditions that do not provide written regulatory approval upon request will be rejected

27.9 Apps conducting health-related human subject research must obtain consent from participants or, in the case of minors, their parent or guardian. Such consent must include the (a) nature, purpose, and duration of the research; (b) procedures, risks, and benefits to the participant; (c) information about confidentiality and handling of data (including any sharing with third parties); (d) a point of contact for participant questions; and (e) the withdrawal process. . . .


Oh my -- it isn't often that I get caught completely slack-jawed by the advancing pace of tech, but tonight I confess -- I am agape. Maybe I'm just getting old, but it sure seems that the world moves so quickly these days. [Not entirely rhetorically -- I wonder whether both Stanford and Apple received calls from FDA staffers today, post the Bloomberg story and the AppleInsider note, earlier in the week.] Sleep well, one and all!

Drug Discovery -- In Entirely New Places? "Merck, Do Take Heed."


Well, it is truly a brave new world. How so?

I see this morning that the Stanford University Medical Research iPhone App garnered 10,000 patient volunteers in its first two nights of availability in the App Store (to conduct large cardiovascular studies).

In the old world, to get 10,000 patients enrolled in a CV study, one would expect that it would take over a year -- and well north of $2 million, in expenses -- just to get a CRO to find that many, and sign them to required informed consent forms. . . before even beginning a study. So, even if we may quibble about how perfect a match these 10,000 iPhone users will be -- compared to the overall populations involved -- that it was accomplished essentially for free -- and in 48 hours -- is positively mind-bending.

As if that weren't enough, I just read that my favorite lil' genome-mapping-by-spit company, 23andMe (the Google non-affiliated-affiliate!) has just signed a Genentech executive to begin. . . drug discovery efforts, using the vast database of genomic information the company now holds. I'll note that he must have gotten a release under his non-compete from Genentech, because 23andMe already has agreed to collaborate with Roche (the parent), through Genentech -- using the 23andMe database for. . . you guessed it -- drug discovery. In fact, this same executive apparently spear-headed that deal. Small world.

This is entirely fascinating -- from Bloomberg -- more later this afternoon:

. . . .23andMe Inc., the Google Inc.-backed genetic-testing startup that popularized a $99 DNA spit test, will expand from screening people for diseases to inventing new medicine to cure them.

The Silicon Valley company has recruited a top biotechnology executive to help. Richard Scheller spent almost 15 years at Genentech, heading research and early development at the company that invented pioneering cancer drugs Herceptin and Avastin. He’ll lead 23andMe’s new therapeutics group.

It’s the latest evolution for 23andMe, which went from a seller of novelty ancestry kits to one of the world’s biggest repositories of genetic data, doing business with major pharmaceutical companies like Pfizer Inc. and Genentech. . . .


We will of course keep the readership posted. Much more shortly above now, but this is. . . a potential game changer.