Novartis blood cancer med receives second FDA approval

Swiss drugmaker Novartis said on Tuesday it received a second approval from the U.S. Food and Drug Administration (FDA) for a second form of the blood cancer drug Kymriah.

The company said it received FDA approval to treat adult patients with relapsed or refractory large B-cell lymphoma.

“Today’s FDA approval of Kymriah provides another opportunity for Novartis to build on its leadership in CAR-T development,” said Liz Barrett, chief executive of Novartis Oncology.

Kymriah, a chimeric antigen receptor T cell (CAR-T) therapy, in August won FDA approval for treatment of acute lymphoblastic leukemia in patients up to 25 years old.

https://reut.rs/2jn8mC0

Valeant Ex-Exec’s Fraud Trial Puts Firm in Uncomfortable Light

The fraud trial of a former executive at Valeant Pharmaceuticals International Inc. is set to begin this week in Manhattan federal court, the first criminal prosecution to emerge from multiple investigations into the embattled pharmaceutical giant over its sales practices.

In this case, prosecutors say Valeant was the victim. Using a statute often applied to public corruption cases, the U.S. attorney’s office in Manhattan has accused the former Valeant executive, Gary Tanner, and a co-defendant, Andrew Davenport, of defrauding Valeant through an alleged multimillion-dollar kickback scheme involving Philidor Rx Services, a specialty mail-order pharmacy.

The defense has said in court filings and appearances that the men were working in Valeant’s interest, developing Philidor as a partner and bringing in “incredible profits” for both companies.

Valeant says it is cooperating with the investigation. “Today, Valeant is focused on improving people’s lives with our health-care products,” a company spokeswoman said.

A spokesman for the Manhattan U.S. attorney’s office declined to comment.

With current and former Valeant employees expected to testify as government witnesses and bids by the defense to put Philidor employees on the stand, the trial could put Valeant in an uncomfortable spotlight, raising questions about the Canadian company as it tries to recover from years of tough scrutiny over its business practices.

For years, Valeant was considered a pioneer in the drug industry, with a business model focused not on discovering new drugs, but on acquiring and selling drugs, often with significant price increases.

Philidor was formed in 2013, and helped Valeant sell some of its higher-priced products by helping patients obtain insurance reimbursement and other financial assistance for prescriptions. While Philidor was in operation, at least 90% of the drugs Philidor dispensed were from Valeant, prosecutors alleged. Philidor, which was based in Pennsylvania, closed in 2016.

The relationship with Philidor wasn’t discussed with Valeant investors until 2015, when questions emerged in the media about the companies’ ties. At the same time, Valeant faced law-enforcement scrutiny and intensifying criticism over drug-price increases.

Mr. Tanner and Mr. Davenport, who had been Philidor’s chief executive, were arrested in November 2016 and charged with conspiring to persuade Valeant to funnel business to Philidor. Prosecutors alleged Mr. Davenport paid Mr. Tanner about $10 million in kickbacks, while Mr. Tanner allegedly used his position at Valeant to facilitate deals that helped Mr. Davenport reap more than $40 million.

In one instance cited in the initial criminal complaint, when Valeant began pushing Philidor for $50 million in overdue payments, Mr. Tanner urged his employer to give Philidor more time. After securing the delay, Mr. Davenport sent Mr. Tanner an email likening themselves to Butch Cassidy and the Sundance Kid, riding “into the sunset…as our wiggle room/ability to operate independently gets whittled down.”

Both men face four counts: honest services wire fraud, honest services wire fraud conspiracy, Travel Act conspiracy, and money-laundering conspiracy.

Prosecutors have alleged in filings and oral arguments the men used shell companies and an alias to conceal the alleged scheme and Mr. Tanner’s financial interest in Philidor, thus depriving Valeant of Mr. Tanner’s “honest services.” Lawyers for Mr. Tanner have argued the government misapplied the honest-services fraud statute in this case.

The statute has been used in federal public-corruption cases, but prosecutors have also applied it in cases where individuals are accused of violating a fiduciary responsibility to a company.

Valeant remains under investigation by federal prosecutors in Manhattan and Massachusetts, the North Carolina Department of Justice, the Securities and Exchange Commission, the California Department of Insurance and Canada’s principal securities regulator, among others, according to recent Valeant SEC filings.

The company has said it is cooperating with those investigations.

Valeant also faces multiple lawsuits, which are on hold pending the trial. The spokeswoman didn’t respond to questions about the litigation.

https://bit.ly/2rfo0mi

Frightening spread of synthetic opioids

According to a research letter in the Journal of the American Medical Association, synthetic opioids have eclipsed non-synthetic opioids in terms of opioid deaths. In this 150-Second Analysis, F. Perry Wilson, MD, discusses the new findings and their implications.

What started as the opioid epidemic in the U.S. is rapidly becoming the synthetic opioid epidemic, and we need to begin to grapple with exactly what that means. The issue is brought into stark relief by this research letter appearing in the Journal of the American Medical Association.

Researchers used data from the National Cause of Death File, which records multiple causes of death as reported on death certificates. Over the past 6 years, deaths from opioid overdoses have increased dramatically, and the proportion of those deaths associated with synthetic opioids has increased as well.

Let’s go back to biochem to remember what synthetic opioids are. Your traditional opioids come, essentially, from the poppy plant.

Morphine, codeine, oxycodone, heroin — all of these are poppy derivatives. But in 1960, Paul Janssen (founder of Janssen pharmaceuticals) synthesized fentanyl in a lab. It was approved for medicinal use in 1968.

Fentanyl is markedly more potent than heroin largely due to its lipophilic nature — it can cross the blood-brain-barrier quite easily. Note the difference in the amount of drug sufficient for a fatal overdose:

The combination of high potency and the ability to synthesize the drug without having to grow a field of poppies has quickly led fentanyl to become one of the most smuggled illicit drugs in the world. A 1-kilogram block of fentanyl can fetch as much as $10 million on the black market, compared with a paltry $200,000 per kilogram of heroin.

What the paper shows is that synthetic opioids are increasingly being found in the system of those who overdose on really any drug.

For example, in the year 2010, 4% of patients who died of a cocaine overdose had synthetic opioids in their system. In 2016, that number was up to 40%.

These highly potent drugs, in other words, are adulterating the entire illicit drug chain. And many users have no idea.

I spoke to lead author Dr. Christopher Jones of the Substance Abuse and Mental Health Services Administration about this very issue: “I think what you’re seeing in the data in the last couple of years is that the illicit drug supply has become substantially more dangerous than it has been, and there’s this level of unpredictability and lack of awareness of what are exactly the substances that people are using that are contributing to the overdose risk,” he said.

There are two issues to grapple with here as physicians. First, we need to educate the public as to just how dangerous synthetic opioids are due to their potency. Second, we need to tell people that other recreational drugs — not just opioids — may be cut with these agents. Most people aren’t expecting to overdose on fentanyl when they do cocaine, but it is a real possibility. First responders also need to be trained to recognize opioid overdose even in the absence of a clear opioid ingestion and be equipped with reversal agents like naloxone as well.

F. Perry Wilson, MD, MSCE, is an assistant professor of medicine at the Yale School of Medicine. He is a MedPage Today reviewer, and in addition to his video analyses, he authors a blog, The Methods Man.

https://bit.ly/2w9wBwu

Express Scripts Cuts Deal to Simplify Cholesterol Med Access

Successfully prescribing the PCSK9 inhibitor alirocumab (Praluent) could get much easier for millions of patients, as Sanofi and Regeneron announced a deal with the nation’s largest pharmacy benefits manager, Express Scripts.

Effective July 1, 2018, the companies will lower the net price (wholesale minus discounts) for Express Scripts’ to within the price point set by the Institute for Clinical and Economic Review for cost effectiveness — $4,500 to $8,000 per year for higher-risk patients with LDL ≥100 mg/dL despite intensive statin therapy.

In exchange, Express Scripts will make alirocumab the exclusive PCSK9 inhibitor for about 20 million commercially-insured people under its National Preferred Formulary. And, the benefits manager will replace the current burdensome prior authorization process with a simpler “attestation” by the physician that the prescription is appropriate based on the FDA-approved indication and patient history. Submitting laboratory results and detailed patient history will no longer be required.

The simplification isn’t just for patients with LDL cholesterol >100 mg/dL at baseline, noted Sheldon Koenig, senior vice president and global head of of Sanofi’s CV Franchise.

Rebates and discounts among pharmaceutical companies, pharmacy benefits managers, and insurers are nothing new. But “this is the most public we’ve ever been with a process like this,” Sheldon told MedPage Today. He called it “significant progress” on a real challenge for physicians and patients.

Beyond just getting the prescription approved, many physicians have seen the PCSK9 prescription abandoned once patients found out the copay. The copay can range from $50 to 20% or 30% of the drug price.

The deal struck with Express Scripts will also add rebates to patients, starting July 1 as well.

“For the first time, patients will receive drug-specific rebate savings at point of sale,” a spokesperson for Express Scripts said. “For example, if someone has an average monthly copay of $150, they would save about $50.”

A spokesperson for Amgen, maker of evolocumab (Repatha), the other approved PCSK9 inhibitor, said in a statement that it was disappointed in the decision that will affect about 2,000 Express Scripts patients currently on alirocumab.

However, the decision applies to only about one-third of Express Scripts business segments, the statement noted. “Amgen can still compete for the other two-thirds where we are continuing to offer significant discounts and rebates on Repatha in exchange for improved patient access.”

Amgen has been “aggressively” negotiating similar deals with several other payers, it added. “We are offering significant discounts that are in line with our competitors and have multiple offers pending.”

https://bit.ly/2HK8GFz

Allergan ads: Do you need to buy branded Botox?

Botox rivals are on the way, and to get out in front of them, Allergan is fielding a new ad push. Its aim: To get would-be users to ask for the blockbuster drug by name. Otherwise, they might get one of its newer competitors instead—and Allergan wouldn’t like that one bit.

Two new spots for Botox Cosmetic—one aimed at men, the other at women—encourage viewers to name-drop the drug at the doctor’s office. In one, a male narrator reminds watchers that, “it’s the details that make the difference,” but “the man makes them matter” as the camera flips through shots of an architect showing his precise work to a child, a runner tying his shoes and setting his watch and a man fixing his collar and tie as he dresses in formalwear.

In the other, a female narrator encourages women to “face the world as a face to be reckoned with” over shots of a dancer practicing in the studio, a photographer shooting photos in the woods and a woman working with colleagues in the office. “Leave your mark on the world. Minimize its mark on you,” the voiceover says as the commercial ends.

Revance Therapeutics spooked Allergan investors in December when its Botox rival, candidate RT002, aced a pair of phase 3 trials. And the smaller company spooked the company again in February when it revealed a tie-up with Mylan to develop a biosimilar of the blockbuster product.

Not all analysts are so worried about Allergan losing marketing share to Newark, California-based Revance. For one, Allergan has a whole suite of aesthetic remedies, and it cuts deals with doctors who use a lineup of them. “[T]he cash-pay bundle of aesthetics products that Allergan offers is a significant barrier to entry” for wannabe rivals, Leerink Partners’ Seamus Fernandez wrote in December.

And then there’s the copycat version itself. RBC Capital Markets’ Randall Stanicky has noted that there are “several outstanding questions” around the Mylan biosimilar and how many of Botox’s many indications, both clinical and cosmetic, it’ll go after.

Plus, Wells Fargo’s David Maris pointed out in January that men and women seeking wrinkle relief already specify the Allergan injection. “[M]any patients demand Botox by brand”—and Allergan aims to keep that trend going with the new ads.

Investors aren’t necessarily buying into that optimism, and physician surveys predicted Revance will capture a good-sized piece of the pie. The “Botox competitive threat is real,” Bernstein’s Ronny Gal wrote in January.

Meanwhile, Allergan is still forging ahead with new uses for Botox, which executives have called a “pipeline in a drug.” In October, it won a FDA green light to temporarily improve the appearance of forehead lines, an indication the company plugs in the new spots.

https://bit.ly/2I9D0gk

Keytruda romps through Q1, but Merck needs fuel beyond the I-O star

On Tuesday morning, Credit Suisse analyst Vamil Divan dashed off a note calling Merck “a story that we believe is currently overly reliant on Keytruda.” The source of Divan’s worry? A first-quarter earnings report dominated by the immuno-oncology blockbuster.

Merck reported revenues for the quarter of $10 billion, in line with expectations, and earnings per share of $1, beating analysts’ estimates by a nickel. Keytruda, a checkpoint inhibitor that’s now approved to treat seven tumor types, brought in sales of $1.46 billion during the quarter, representing 151% year-over-year growth and easily surpassing average forecasts of $1.37 billion.

“We’re pleased that due to the strong execution we’ve had, Keytruda has the potential to be the largest product Merck has ever had,” said CEO Kenneth Frazier during a conference call with analysts after the earnings report.

Perhaps, but the product’s success hasn’t translated to shareholder return, one analyst pointed out during the call. Merck’s stock has fallen 6% over the past year, for example, while the S&P 500 has gained 11%. And even though Merck’s shares have advanced nearly 30% in the last five years, the S&P has risen more than 63% during that time.

Concerns about over-reliance on Keytruda were only compounded this quarter by a couple of notable under-performers in Merck’s lineup. Sales of the company’s hepatitis C treatment Zepatier came in at $131 million, way below the consensus estimate of $236 million. The product faces a tough new rival in AbbVie’s Mavryet, which brought in a whopping $919 million during the quarter—nearly double what analysts were expecting.

Merck’s shingles vaccine Zostavax is also struggling in a competitive market. Sales of Zostavax were $65 million during the quarter, missing the consensus estimate of $106 million, as GlaxoSmithKline snaps up market share with its newly approved vaccine Shingrix.

Frazier said during the call that he’s as frustrated as analysts are about Merck’s stock performance, but he doesn’t believe the company’s growth opportunities are limited. And dealmaking is playing a role in his plans. The company’s business-development strategy, he insisted, positions Merck for “long-term growth and value creation,” and its future revenue opportunities “are somewhat underappreciated,” he said. “We continue to look for opportunities to augment our growth in our pipeline through business development.”

Merck has shied away, however, from “transformational deals”—read multibillion-dollar mergers—a strategy that many have questioned. Instead, it has racked up a series of alliances designed to build its pipeline in key areas, not the least of which is immuno-oncology. The most recent such deal was its $394 million purchase of Viralytics, an Australian company that’s testing a cold virus in combination with Keytruda.

So how can Merck unlock more shareholder value? One obvious choice could be spinning off its animal health business. That unit did well in the first quarter, with revenues growing 13% year over year to $1.1 billion. Both its companion- and farm-animal products grew, it reported.

But Frazier has been reluctant to bid animal health goodbye—an instinct that he said he trusts even more now that investors are pressuring Merck to think beyond Keytruda.

“Our goal over the longer term is to drive long-term growth, and we think animal health—a business that generates really good cash flows that actually helps fund the human-health R&D—is a way of generating long-term shareholder value,” he said. “I guess, ironically … this provides diversification from Keytruda as well as the rest of our human-health portfolio.”

https://bit.ly/2Fzn1T5

Pfizer first-quarter results miss estimates as key drug sales fall short

Pfizer Inc (PFE.N) on Tuesday reported lower-than-expected first-quarter revenue as demand for some key drugs and international sales fell short of estimates, sparking a 5.1 percent drop in shares of the largest U.S. drugmaker.

The company, which is exploring a sale of its consumer healthcare business but has seen potential suitors drop out, said it has not received an acceptable offer at this time.

“If we can’t get value, we’ll retain it and invest in it,” Chief Executive Officer Ian Read told analysts. A final decision is still expected this year.

Read, whose previous attempts at huge acquisitions of AstraZeneca (AZN.L) and Allergan (AGN.N) were thwarted, said the company does not need a megamerger to drive future growth.

“I don’t see that we need a transformative deal or see one at an appropriate value,” Read said, adding that drugs in development and newer medicines will be able to drive future growth.

He said the company has 15 potential blockbuster medicines in the pipeline that could be launched by 2022.

Pfizer also sees opportunities to significantly expand sales of prostate cancer drug Xtandi for treating less advanced patients, and arthritis drug Xeljanz for ulcerative colitis. U.S. regulatory decisions on the expanded uses are expected later this year.

Pfizer posted adjusted earnings of 77 cents per share that topped analysts’ average expectations by 4 cents, according to Thomson Reuters I/B/E/S, on lower taxes and cost of goods sold. It did not raise its full-year earnings or revenue forecasts.

Despite strong growth, sales of oral rheumatoid arthritis drug Xeljanz and blockbuster breast cancer treatment Ibrance missed expectations largely due to inventory stocking issues but are likely to rebound, analysts said.

Injected arthritis drug Enbrel was hit by competition from cheaper biosimilars outside the United States. Vaccines and other older drugs, such as Lyrica, Premarin and Celebrex all fell short of analysts’ estimates.

Ibrance sales rose 37.4 percent to $933 million, while analysts looked for $956.6 million. Xeljanz sales totaled $326 million, missing the Wall Street outlook by about $72 million.

Total revenue rose 1 percent to $12.91 billion, while analysts expected $13.13 billion.

SunTrust Robinson Humphrey analyst John Boris said he expected stronger international sales, given favorable foreign exchange rates.

“If you remove the FX tailwind it would have been a much more substantial miss,” he said, adding that it was disappointing Pfizer did not raise its 2018 forecasts after rivals, such as Merck & Co (MRK.N) and AbbVie (ABBV.N), raised their outlooks after reporting first-quarter results.

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Pfizer still expects adjusted full-year earnings of $2.90 to $3.00 per share on revenue of $53.5 billion to $55.5 billion.

Net profit rose to $3.56 billion, or 59 cents per share, for the quarter, from $3.12 billion, or 51 cents, a year earlier.

https://reut.rs/2JHMZX1