Advaxis’ Immune Oncology Program Candidate, In New Combo-Studies, With Merck’s Pemrolizumab: Prostate Cancers

August 30, 2014 - Leave a Response

Yet another class of cancers will now be studied in an immuno-building combination, along with MK-3475 — Merck’s single most promising drug candidate, across the entire company. [And this tidbit comes to us from a kindly anonymous commenter. My regular readers are. . . the best!]

Once again, this bit of news broke while I was traveling, last week. But here it is, from the Advaxis presser — Advaxis’ candidate is called ADXS-PSA:

. . . .Both ADXS-PSA and pembrolizumab are investigational members of a new class of cancer treatments known as immunotherapies that are designed to enhance the body’s own defenses in fighting cancer. Preclinical evidence suggests that Advaxis Lm-LLO immunotherapies in combination with a PD-1 inhibitor may lead to an enhanced anti-tumor immune response.

“We are excited to be working with Merck. Equally as exciting is the combination potential of our Lm-LLO immunotherapy with Merck’s anti-PD-1 immune checkpoint inhibitor,” commented Daniel J. O’Connor, President and Chief Executive Officer of Advaxis. “We believe the combination of Advaxis Lm-LLO cancer immunotherapies and checkpoint inhibitors holds significant promise for the treatment of prostate and other cancers.”

Under the terms of the agreement, Advaxis and Merck will collaborate to evaluate the ADXS-PSA/pembrolizumab combination as a treatment for prostate cancer. The Phase 1 part of the trial is designed to establish a recommended dose regimen for ADXS-PSA alone and combined with pembrolizumab, and the Phase 2 portion will assess the safety and efficacy of the combination. Advaxis will sponsor and fund the study and Merck will provide pembrolizumab. The companies will collaboratively oversee the conduct of the study, which is planned to begin in early 2015. Results from the study will be used to determine the path for further clinical development of the combination. . . .

[And just a bit more, from an Onc-Live interview:]

. . .[Advaxis' approach to attacking] immune tolerance involves cells that live inside tumors and send out clouds of biologic chemicals that also can shut down activated T cells in the area. Scientists know these as Tregs and MDSC cells. Even if the T cells get past the PD-1 [which MK-3475 is designed to address] they can still be shut down by Tregs and MDSCs in the tumors. ADXS-PSA has the ability to decrease the number and activity of Tregs and MDSCs inside the tumors in tumor models.

The point behind this combination is that ADXS-PSA stimulates the immune system to generate a new crop of cancer-fighting T-cells that recognize a key target on the tumor cells, PSA. Then the pembrolizumab PD-1 blockade masks PD-1, which the tumor may be hiding behind, and amplifies the number of cancer fighting cells that are produced. Once these cancer-fighting cells get inside the tumor tissue itself, past the PD-1 blockade, they find that the ADXS-PSA had disabled the Tregs and MDSCs inside the tumor, allowing the cancer-fighting cells to do their job and eliminate cancer cells. Therefore, the combination treatment provides a fresh crop of cancer-fighting cells, while at the same time, overcoming two different mechanisms of immune tolerance that could be protecting the prostate cancer inside patients. . . .

Financial terms were not disclosed — but the Advaxis oncology candidate has a nice pedigree. We will watch it closely. And, interestingly, a good portion of the management team (and board) had deep ties to the former ImClone — acquired by Lilly some years ago. Now you know. One to watch.

[Just as trivia, as I close out, and head off to bed -- the older Advaxis logo (circa 2011) was unabashedly a Trojan Horse (see small image at lower left, of the main image). That stark (and perhaps provocative) imagery has been softened, muted and stylized -- in the new logo (top left) -- and I can certainly see why. I suppose the company thinks of its cancer killer as using a "Trojan Horse" approach -- to re-ignite the body's own immune system. Still risky imagery (in my view), for a bioscience company. Smile. G'night, one and all of good will.]

Tiny Matters: Most MSM Outlets Misunderstand the UK Takeover Regs Timelines

August 30, 2014 - Leave a Response

I’ll not expend an undue flow of electrons on it here, but in my estimation, there is almost no chance of a September renewal of the foundered Pfizer hostile deal, for AstraZeneca. In short, AZ has no reason to invite Ian back. And that’s what the UK Takeover Code would require (at this moment, anyway). [Two of many backgrounders, here, and here.]

Here is one of the more confused reports — it has the three- and six- month re-engage dates exactly backwards. AZ must have voluntarily invited Pfizer back to the table — if talks are to resume this coming Tuesday. And there is not a snowball’s chance in August — in Dallas, Texas, of that (in my not so humble opinion). And so now, I’ve reordered and edited the above Bidnezz(!) story, to make it passingly accurate, as to UK law. November 26 Pfizer may ask AZ to re-engage. And AZ may (and likely will) decline.

. . . .The [UK Takeover Code] regulations allow would-be acquirers to make a one-time offer [if] the target [has] invite[d] [the acquirer] back to the table, [at three months]. In most cases, UK takeover regulations allow companies to re-engage with one another once a mandatory six-month cooling off period expires. . . .

AstraZeneca also has the option to reengage in talks with Pfizer with a proposed sale offer [by inviting Pfizer back as of August 26 -- which I say is unlikely]. The companies will not have any regulations applicable on them from November 26 onward, when the six-month cool off period ends. . . .

Um. . . pronouns matter.

AZ’s checkpoint inhibitor (oncology) program posted spectacular data, at ASCO in June 2014. A strong business case may now be made that Pfizer needs AZ far more than the other way around. And that will put the board of AZ in a very sound position to talk politely for a bit to Ian, then just say. . . no. That checkpoint inhibitor candidate — much like the BMS and Merck similar PD-1 receptor candidates — has the real potential to reshape the treatment of cancer, globally. And AZ could garner perhaps $10 billion a year in peak oncology sales from it. No need to share that with wee ole’ man Ian. Q.E.D.

A New Analyst Firm’s Coverage Of Merck: Deutsche Bank Starts At $65

August 30, 2014 - Leave a Response

Okay, during the week (while I was out, on Wednesday), Deutsche Bank began coverage — on Merck.

Deutsche Bank has a “hold” on the name, with a target of $65. That makes sense, given that Merck has now touched — and surpassed the $60 mark.

Two things that $60 event imply: One, Merck’s dividend yield is now just under three per cent. . . generally a good thing (Merck is both a growth stock, and yet a pretty fat dividend payer!) — and two, the Bank’s 12 month target is actually only like seven per cent above Friday’s close. Still a suggestion that Merck is pretty fully valued here. Just my $0.02. [I could wax cynical, and suggest that the bank would like to win some debt underwriting business from Merck (for the other side of its house), and so put a slightly outsized target on Merck's price -- I think $65 is the top quote at the moment. But I'll restrain my cynicism.]

Now At Least Two Pfizer Pembro-Collaboration Projects Are Known. . .

August 26, 2014 - Leave a Response

This from that erstwhile gent Ed Silverman, over at Pharmalot (see below, but do go read it all).

Longer term, the race will be won by the company that gets approval in the heaviest burden cancers. But both BMS and Merck are lead pipe cinches to win approval — and likely before year end 2014, for each.

. . . .The agreement comes days after Bristol-Myers Squibb Co. and Celgene Corp. said they agreed to collaborate on a clinical study for a treatment that would combine immunotherapy and chemotherapy to combat pancreatic, lung and breast cancers.

Pharmaceutical companies are jockeying for position in the rapidly growing cancer-treatment market. Immunotherapy, which uses immune systems to fight the disease, is driving much of the expansion.

Merck said in February that it had reached three separate agreements to collaborate on studies of pembrolizumab in in combination with therapies from Pfizer, Amgen Inc. and Incyte Corp. The company has sought to test the drug for effectiveness on a wide range of cancers.

The study announced Tuesday will test a combination of Merck’s investigational antibody pembrolizumab and Pfizer’s crizotinib, also known as the brand name Xalkori, which is indicated for the treatment of nonsmall-cell lung cancer. . . .

As ever, we will keep an eye on the BMS-generated nivolumab progression, which has been excellent — outstanding, in fact — as well. Most informed watchers grant the overall efficacy nod to BMS’s candidate, to be fair.

Pre-Arranged Stock Sales By Merck Executives — Pursuant To SEC Recognized Plans — Mean Very Little. Yawn.

August 25, 2014 - Leave a Response

Okay — like the others (most recently, two weeks ago — by the Chairman & CEO), this is an algorithm trade. Mr. Schechter had pre-set this trade, likely via formulae, in my experienced guestimation.

His trade executed today, August 25, 2014.

. . . .Adam Schechter Pres. Global Human Health | 22,000 shares @ $59.69. . .

This thus means. . . Nothing. And speaking of meaning nothing — today’s Reuters’ rumor piece — about the possibility of an earlier than October 28 FDA approval date for pembrolizumab, seems to be much ado about nearly nothing. When it happens, we will all know. Same way with nivolumab. I can say that no FDA Advisory Committee date has been set; and in the same breath, I can say that in this case (under applicable FDA rules) FDA could approve it without an Advisory Committee vote. Now, be safe out there.

Small PSA — These Nine Fosamax® ONJ Plaintiffs Should Call Their Lawyers

August 21, 2014 - Leave a Response

It seems that several plaintiffs have “opted in” — i.e., elected to accept — the global Fosamax® ONJ settlement, but their paperwork is — in various ways — deficient (or, at least Merck so alleges).

So Merck would like the very able Judge John F. Keenan, sitting in the federal trial-level courthouses in Manhattan, to give them a period of time to cure, and then if they do not — dismiss them without any payments, from the common settlement fund.

That process began in earnest, Tuesday. The affected plaintiffs are: (1) Claudette Williams, (2) Robin Swolley, (3) Susan Sloan, (4) Audrey Minzer, (5) Naheed Khan, (6) Lowell Howell, as Personal Representative for Mildred Robinson, Deceased, (7) Doris Hanke, (8) Susan Doyle, and (9) James Corbett, as Personal Representative for the Estate of Ivy Corbett. Do contact your counsel, one and all.

. . . .ORDER: On August 15, 2014, Merck served a motion for a new Lone Pine order, this one targeted at nine plaintiffs who initially opted into the global settlement but whose paperwork is allegedly deficient.

Counsel for the affected plaintiffs are directed to file a response indicating whether they oppose the motion by August 29, 2014.

Any reply by Merck must be filed by September 5, 2014.This Order should be entered on the docket of 06 MD 1789 as well as on the dockets of the individual cases listed in the attached table. (Responses due by 8/29/2014, Replies due by 9/5/2014.)

(Signed by Judge John F. Keenan on 8/19/2014). . . .

Separately (and perhaps immodestly — I’ll report that) overnight, the National Law Journal has picked up my scoop on the Incretin Mimetic MDL discovery/adverse event source documents spat. Safe travels all day, one and all, as well.

Incretin Mimetic Drugs MDL Wends Its Way Forward, In Southern California USDC

August 20, 2014 - Leave a Response

We will start to cover this bit of litigation more regularly now. It seems that over the course of the last year and a half, in the Southern District of California, in the federal courthouses, there have been various prodeedings in a multi-district litigation concerning the risks allegedly associated with so-called incretin mimetic drugs like Merck’s Januvia®. [My March 2013 backgrounder. I still think the outcome (if any) in this litigation will not materially impact the franchises' sales revenue. On the other hand, various other developments may -- including certain provincial Canadian reimbursement machinations, and the appearance of India-sourced generics -- of the same class. So keep an eye on those narratives, as we will too.]

Back to the main topic here — the litigation has progressed to the point that motions to compel the disclosure of adverse events documents (required to be collected by the manufacturers, and in certain circumstances, filed with FDA) are now pending.

The despositive hearing on those motions will occur at 2 PM PDT, in Los Angeles, on October 9, 2014 — unless Merck and the other manufacturers agree to deliver the documents, without an order. We will check in again on the 26th, to collect, read and analyze the reply brief — but here is the entire briefing schedule:

. . . .ORDER by Judge Battaglia, Set briefing schedule as to Motion to Compel Discovery of Adverse Event Source Documents and Databases.

Oppositions due by 8/26/2014

Replies due by 9/9/2014, no sur-replies will be filed.

Motion Hearing set for 10/9/2014 at 2:00 PM in Courtroom 3B before Judge Anthony J. Battaglia. . . .

As ever, we will keep a weather-eye on this, for the readership. Stay cool in the that southern heat, now.

UPDATE: The New Jersey Law Journal Is Running My Scoop

August 19, 2014 - One Response

The MSM outlet — New Jersey Law Journal – adds a nice new level of detail, going into additional background on the motion, here. Do go read it all — but below is a bit.

The article is not as clear as it could be in distinguishing the femur cases from the ONJ (and all other) ones. This motion applies only to the femur cases.

. . . .The court should order all remaining plaintiffs to show cause why their claims should not be dismissed on federal preemption grounds, in light of the court’s ruling in Glynn’s case, Merck said in its brief. Alternately, any remaining cases in which plaintiffs used the drug after the 2011 label revision should show cause why their claims should not be dismissed for reasons stated by the court in Gaynor’s case, Merck said.

Although Gaynor’s case was decided based on laws of the state of New York, where Gaynor resides, the ruling “is based on fundamental principles that all states recognize—most notably, that a plaintiff cannot prevail for failure to warn if the warning label at issue warned of the very injury she allegedly suffered,” Merck said in its brief.

Following ruling in Glynn’s case, Pisano granted Merck’s motion to dismiss roughly 650 cases involving alleged injuries occurring before Sept. 14, 2010 on preemption grounds. Merck said in its Aug. 15 brief that its prior motion was limited to that group of cases on the assumption that plaintiffs who claimed later injuries would base their claims on the contention that the revised warning label issued in January 2011 was inadequate. However, earlier this year, plaintiffs lawyers in the case indicated that “no plaintiff alleges that the January 2011 label was a proximate cause of his or her injury,” Merck said. . . .

We will — of course — watch this for the readership. There were about 1,280 femur cases still pending as of the end of Q2 2014, according to Merck’s latest SEC filed Form 10-Q.

Merck Moves To Dismiss All Remaining Femur Fracture Fosamax® Cases — Claiming Preemption/FDA Warning Label Adequacy

August 18, 2014 - Leave a Response

In the aftermath of the Supreme Court’s Wyeth v. Levine decision, we will likely see more of this sort of argument. [And one of my many earlier 2014 backgrounders.]

Merck’s lawyers — as of last Friday — formally moved to dismiss all remaining Fosamax® femur claims by suggesting that prior to 2011, Merck was prohibited from changing an older warning/FDA label, by then applicable law, without FDA’s prior written approval. And it could not get FDA approval for the change, at the time. Then, over a year later, the FDA approved Merck’s changes, and Merck made the changes — essentially pre-empting all remaining warning claims, under the Supreme Court’s reasoning (if not actual holding) in Levine. Here is the full 36 page PDF filing, from Merck’s trial counsel.

What I imagine this leaves for the injured plaintiffs, should Merck prevail here — is a claim against the prescribing doctor, only. A smaller pot. True enough, in the end, the doctor ought to be responsible for keeping up with the evolving literature showing increasing risk of “brittle bones” injuries on long term Fosamax therapy, I suppose. We will track the progress of this motion in the New Jersey federal District Courts. A tough Monday, all the way around.

Sunday Fare: What’s Up On August 20, At The Federal Propecia® MDL Hearing?

August 17, 2014 - Leave a Response

On August 20, 2014, in the Eastern District of New York, Merck’s lawyers will appear to defend it at this federal MDL status conference on the 1,280 some Proscar®/Propecia® (mostly) sexual dysfunction lawsuits.

Probably the most significant item on the agenda is setting a discovery and trial calendar order. We will keep you posted.

. . . .The parties jointly submit the following agenda for this Court’s August 20, 2014 Status Conference.

1. Argument on Plaintiffs’ Motion to Compel;

2. Exhibit A to the Proposed Common Benefit Order;

3. Proposed Discovery and Trial Plan Procedures and Practice Order; and

4. Defendant’s Administrative Motions to Dismiss. . . .

Off to workout and — after that — eat a big southern breakfast. Do get out, and enjoy these dog days of August. And. . . we will certainly meditate, in the evening — for a largtely-peaceful night to pass, tonight, in Ferguson, Missouri.

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