Purdue Pharma in talks to settle DOJ opioid probes – WSJ

The Wall Street Journal reports that OxyContin maker Purdue Pharma LP is in discussions with the U.S. Justice Department to settle criminal and civil investigations over its role in the opioid epidemic.

Any agreement will likely include a monetary fine, potentially diluting compensation sought by state and local governments who claim that the company’s aggressive marketing of the painkiller was a significant contributor their respective opioid addiction problems.

The company and Sackler family owners have proposed a payment of $10B – 12B to settle all suits by states and local governments, to be implemented through a bankruptcy and paid out over a period of years. Some states, notably New York, Connecticut and Massachusetts, have balked at the amount, a sum they say is short of what’s needed.

Selected tickers: Teva Pharmaceutical Industries (TEVA +1.6%), Johnson & Johnson (JNJ -0.3%), Endo International (ENDP +39.8%), AmerisourceBergen (ABC +0.2%), McKesson (MCK +1.5%), Cardinal Health (CAH +2.2%)

https://seekingalpha.com/news/3497747-purdue-pharma-talks-settle-doj-opioid-probes-wsj

Mallinckrodt agrees to settle ‘Track 1’ Ohio opioid cases

The NYSE suspended trading in Mallinckrodt (MNK +10.1%) pending the release of news.

Update: The company has agreed in principle to settle “Track 1” opioid cases in Ohio by paying $24M in cash plus $6M of donated generic products, including meds to treat opioid addiction.

Update: Shares are up 13% on resumption of trade.

https://seekingalpha.com/news/3497714-mallinckrodt-shares-halted-pending-news

Perrigo Prevacid deal stokes buying in generic players

Perrigo (PRGO +3.3%) adds to yesterday’s 3% jump on the heels of its acquisition of U.S. OTC rights to Glaxo’s heartburn med Prevacid (lansoprazole). Bargain hunters apparently like the deal and are behaving as if they perceive a rosier outlook for the beaten-down group.

Selected tickers: Aclaris Therapeutics (ACRS +9.7%), Amphastar Pharmaceuticals (AMPH +2.9%), Amneal Pharmaceuticals (AMRX +9.3%), ANI Pharmaceuticals (ANIP +0.7%), Bausch Health Companies (BHC +2.3%), Coherus BioSciences (CHRS +0.6%), Eagle Pharmaceuticals (EGRX +0.6%), Endo International (ENDP +16.7%), Lannett Company (LCI +11.4%), Mallinckrodt (MNK +5%), Mylan (MYL +0.7%), Pfenex (PFNX +6.4%), Dr. Reddy’s Labs (RDY +1.8%), Teva Pharmaceutical Industries (TEVA +3.1%)

https://seekingalpha.com/news/3497699-perrigo-prevacid-deal-stokes-buying-generic-players

Teva’s $235M overturn in GSK patent case has appeals judge ‘bewildered’

Facing claims it induced doctors to prescribe a generic version of GlaxoSmithKline’s Coreg that violated its patents, Teva was hit with a hefty $235 million penalty in 2017. But a federal judge overruled that jury’s verdict last year—and now, one federal appeals judge says she’s “baffled” by the decision.

During an appeals hearing Wednesday in GSK’s suit against Teva, a federal judge on the U.S. Federal Circuit Court’s panel in Washington, D.C., said she was “bewildered” by U.S. District Judge Leonard P. Stark’s decision to strike the jury’s original verdict.

The Circuit Court judge, who was not identified in a recording of the proceedings, said she couldn’t “imagine a stronger case for induced infringement” of a drug’s patent. Press releases Teva issued before and after its generic Coreg approval presented its copycat as an “equivalent” to the branded drug despite GSK’s patent protection, she pointed out.

“What was Teva’s intent when it issued those releases?” the judge asked a lawyer representing Teva. “Just goodwill? To let the world know? Or to let doctors know so they could prescribe this drug?”

The lawyer told the judge Teva never attempted to present its generic as exactly the same as Coreg and only issued the press releases to inform physicians that a generic was expected to enter the market.

A Teva spokesperson declined to comment on the case Thursday.

The harsh words from the three-judge panel adds a new wrinkle to the patent “carve out” suit Teva hoped it was rid of back in March 2018, when Stark ruled in its favor. Teva had cited all three of Coreg’s approved indications on its generic’s 2011 label, despite the fact that GSK still had patent protection on its heart-failure use.

Stark said a Delaware jury should not have concluded that Teva’s published releases beguiled doctors into infringing GSK’s patent, both before the generic’s label rewrite—when heart failure wasn’t on its indications list—and after. Stark argued that GSK had not presented sufficient evidence to prove that “even at least one” doctor had been induced to prescribe the generic.

GSK’s Coreg, initially approved in 1995, eventually racked up green lights to treat hypertension, left ventricular dysfunction following a heart attack and congestive heart failure. GSK only marketed Coreg for congestive heart failure in the U.S., and Teva’s generic wasn’t approved to treat congestive heart failure because of remaining patent protections.

GSK’s heart failure patents were in force through 2015. But in 2011, the FDA instructed Teva to rework its label, and Teva’s revised version included that heart failure use.

GSK sued for infringement during both the “skinny label” and “full label” periods and prevailed in a jury verdict in 2017. On Wednesday, the federal panel of judges appeared split in their deliberations.

The GSK suit is just one of a suite of lawsuits and scandals Teva has faced in recent years—a revolving door of legal troubles that has sent investors scrambling for the exits.

In mid-August, Teva’s share price approached a 20-year low as looming federal opioid lawsuits threaten the drugmaker’s bottom line and Moody’s debt-rating agency lowered its outlook for the company from “stable” to “low.”

Moody’s said possible opioid settlements reaching into the billions of dollars could hamper Teva’s ability to pay back its $2 billion in debt that will mature over the next two years.

https://www.fiercepharma.com/pharma/i-m-quite-frankly-baffled-teva-s-235m-patent-infringement-overturn-leaves-judge-bewildered

Takeda recalls eye med Natpara, warns patients not to abruptly stop treatment

Takeda Pharmaceutical’s been looking for a buyer for Natpara to provide some debt relief, but it has just run into some complicating circumstances. It is having to recall the eye drug from the market, a move it says may be very challenging for patients.

Takeda today announced it was voluntarily recalling all doses of the injected drug in the U.S. because there was a chance of small rubber particles shedding into the injectors.

But the Japanese drugmaker was adamant that patients mustn’t stop the treatment abruptly because of the danger of a sudden drop in blood calcium levels. Instead, patients must have their doctor replace the drug with supplements and carefully monitor their calcium levels with blood tests.

“It is critically important that patients contact their prescribing healthcare provider to discuss their individual treatment plan and ensure close supervision including frequent monitoring of blood calcium levels and close titration of active vitamin D and calcium supplements upon stopping Natpara to avoid low blood calcium (hypocalcemia),” the company said.

The particles are coming from the rubber covering, or septum, in the injection cartridge. The company said that when the septum is repeatedly punctured during the 14-day treatment period, it is possible that small rubber fragments may get into the cartridge.

Takeda said it is working with the FDA to resolve the manufacturing issues that have resulted in the recall and to resume production and supply of the drug as quickly as possible.

The difficulty is that there is no alternative treatment for some patients. Natpara, a recombinant human protein, is the only drug approved in the U.S. for adults with the sometimes fatal chronic hypoparathyroidism for whom standard therapy alone is not working.

Takeda said it also is working with drug regulators in other countries where Natpara is approved, but that the drug is not being recalled in those markets at this point.

The supply interruption comes even as Takeda reportedly was looking to sell the drug as a way to improve its balance sheet after its $58 billion buyout of Shire last year. The deal was opposed by many investors because of the debt Takeda had to take on to make the buy.

Novartis provided Takeda some relief when it bought the Shire dry-eye drug Xiidra in a deal that ultimately could be worth $5.3 billion. The Swiss drugmaker also took on 400 ex-Shire employees to help it market Xiidra and the rest of its growing ophthalmic portfolio.

https://www.fiercepharma.com/manufacturing/takeda-recalls-eye-drug-natpara-but-warns-patients-not-to-abruptly-stop-treatment

Novartis, Spark gene therapies win a boost with soup-to-nuts Cigna coverage

A recent controversy over data manipulation during the development of Novartis’ new gene therapy, Zolgensma, has overshadowed another issue pressuring the spinal muscular atrophy (SMA) treatment: its $2.1 million price.

But Zolgensma’s sticker price remains a hurdle—and the same goes for the high cost of the other gene therapy on the market, Spark Therapeutics’ $850,000 eye drug Luxturna.

Fortunately for Novartis and Spark, one major payer, Cigna, says it has figured out how to cover those two pricey treatments. Even better? It’s at no cost to patients.

Cigna announced that patients who receive Zolgensma or Luxturna will be fully covered, with zero out-of-pocket costs. The new gene therapy program will bring together services from many of Cigna’s business segments, including the pharmacy benefit manager Express Scripts, to offer patients “personalized and expert care,” the insurer said in a statement.

Steve Miller, M.D., chief clinical officer of Express Scripts and a longtime critic of rising drug prices, said expensive therapies for rare diseases remain a growing challenge for the healthcare system. Cigna acquired Express Scripts for $67 billion last year.

“The trouble is, while [gene therapies] are incredibly innovative and very effective, they are wildly expensive,” Miller said in a video posted on Express Scripts’ website. “Just like the pharmaceutical companies have been very innovative in bringing these products to the marketplace, we have to be equally innovative in figuring out how we make them accessible and affordable for the patients and their families.”

Under the Cigna program, health plans will pay for the gene therapies on a per-member, per-month schedule. In the video, Miller called it a “cost-recovery” model for Cigna. “So we are not looking to profit off this,” he said.

The Cigna plan marks the second piece of good reimbursement-related news in as many days for Novartis. The company markets Spark’s Luxturna outside the U.S., and Wednesday, England’s National Institute for Health and Care Excellence (NICE) said it would back the drug.

Zolgensma is not yet approved in Europe—Novartis is expecting a verdict in the fourth quarter—but the company will no doubt face reimbursement challenges there as well. To win NICE’s backing for Luxturna, it had to offer England’s National Health Service a confidential discount.

As for the ongoing data-manipulation drama, Novartis is still working to calm regulators’ nerves. In August, a newly released FDA report revealed details about how some data from a mouse study of Zolgensma had been inaccurately reported. The FDA has said it believes the treatment is safe and effective, and it will remain on the market, but the agency is weighing civil or criminal action.

AveXis President David Lennon told analysts in August that the European Medicines Agency is aware of the FDA’s investigations into the Zolgensma data issues and that he doesn’t expect any delays in the approval of Zolgensma in Europe

Novartis is so optimistic about gene therapy, in fact, the company’s executives reportedly told journalists in Germany this week that gene and cell therapies would ultimately account for 15% of total revenues. It has a long way to go, however: Novartis’ CAR-T treatment for blood cancer, Kymriah, has brought in just $103 million of the company’s $23 billion in sales so far this year.

Novartis has not yet announced sales numbers for Zolgensma. In July, CEO Vas Narasimhan would only say the launch is “on track” and in line with expectations.

Cigna’s new payment plan for gene therapy will no doubt be viewed as good news for Roche, too, as it works to complete its planned $4.8 billion acquisition of Spark. The company has delayed its tender offer several times, citing antitrust investigations, but it still expects to seal the deal by the end of the year.

Meanwhile, Cigna’s Miller remains vocal on the high cost burden presented by new gene therapies. Two years ago, he noted that there were more than 1,000 gene therapies in the biopharma pipeline, and clearly he’s still worried about how the health system will pay for them. Cigna’s new program, he said in the video, “just takes care of the first two [gene therapy] drugs that are in the marketplace, but we know many drugs are behind that.”

https://www.fiercepharma.com/pharma/cigna-gives-gene-therapies-novartis-and-spark-a-boost-comprehensive-payment-plan

Autolus Publishes Data on Novel CAR-T AUTO1 Leukemia Treatment

 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, on Tuesday announced that the journal Nature Medicine has published both pre-clinical results and clinical data from the ongoing Phase I CARPALL trial of AUTO1, demonstrating the potential of the company’s novel CAR T therapy targeting CD19 in development for the treatment of pediatric acute lymphoblastic leukemia (ALL).  The paper reports that AUTO1, or CAT Chimeric Antigen Receptor T cells (CAT CAR T), utilizes a binder with a fast off rate and showed both increased proliferation/cytotoxicity in vitro and enhanced proliferative capacity and anti-tumor activity when compared to FMC63 CAR T therapies in vivo.  In the Phase 1 clinical trial, 86% (n=14) of recurrent/refractory pediatric ALL patients achieved molecular complete remission after a single dose, with a median duration of remission of 7.4 months and no severe cytokine release syndrome (CRS; ≥ grade 3 or 4), in this relapsed and/or refractory patient population.

“The safety profile emerging from this pediatric study is encouraging.  AUTO1 was well-tolerated and we did not see severe cytokine release syndrome or neurotoxicity seen in other ALL programs,” said Sara Ghorashian, PhD, Molecular and Cellular Immunology Section, UCL Great Ormond Street Institute of Child Health and a co-author of the paper.  “It is very promising to see these strong remission rates and excellent CAR T cell expansion and persistence, which give us hope that AUTO1 could improve outcomes for these patients.”

“The publication in Nature Medicine is a nice validation of our AUTO1 pre-clinical and Phase 1 clinical data,” said Dr. Christian Itin, chairman and chief executive officer of Autolus.  “AUTO1 CAR- T cells are designed to effectively engage leukemic cells while avoiding excessive immune stimulation. This profile results in an improved safety profile compared to current treatments, while achieving a high level of clinical activity.  We are currently testing the activity of AUTO1 in adult patients who typically are even more susceptible to severe immunological adverse events than pediatric patients.”

https://www.globenewswire.com/news-release/2019/09/03/1909704/0/en/Autolus-Announces-Publication-in-Nature-Medicine-of-Data-Supporting-the-Development-of-AUTO1-for-Treatment-of-Patients-with-ALL.html