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Monday, September 30, 2019

Drugmakers Eye Purdue Pharma’s Bankruptcy to Settle Opioid Suits

Endo International PLC, Johnson & Johnson and other drugmakers that face sprawling litigation over the opioid crisis are exploring a way to settle the cases by participating in Purdue Pharma LP’s bankruptcy, according to internal documents and a person familiar with the matter.
The move, if successful, could bring an end to — or at least dramatically shrink — one of the largest and most complex pieces of litigation the U.S. has ever seen.
Drugmakers and distributors face some 2,500 lawsuits brought by virtually every state as well as cities, counties, Native American tribes and others accusing the pharmaceutical industry of helping fuel widespread opioid addiction.
The cases have become political flashpoints as communities look for ways to recover money to address the costs of treating addiction, including overstressed hospitals and first responders and to care for babies born with opioid dependence.
Five drugmakers battling the cases — Endo, J&J, Teva Pharmaceutical Industries Ltd., Allergan PLC and Mallinckrodt PLC — are looking to enact a global settlement of the litigation that would be implemented through OxyContin maker Purdue’s chapter 11 case, according to a person familiar with the matter. The mechanism, if successful, would allow the companies to contribute money into a trust set up through the bankruptcy in exchange for a complete release from liability.
The idea is still in the early stages, the person said, and no dollar figures have yet been discussed. The concept would need buy-in from Purdue and its owners, the Sackler family, as well as a critical mass of state attorneys general and local municipalities suing the companies. The bankruptcy judge overseeing Purdue’s case would also need to agree he has jurisdiction to allow the other companies into the case.
A Purdue spokesman declined to comment.
Endo is working with lawyers at Skadden, Arps, Slate, Meagher & Flom, the company’s longtime corporate counsel, on the proposed deal, according to internal documents and a person familiar with the matter.
Endo, which makes the opioid painkiller Opana, isn’t considering filing for bankruptcy, the person said, though it faces significant debt.
Purdue, which has been the primary target of plaintiffs in the opioid litigation, entered bankruptcy court in mid-September to implement a multibillion-dollar deal with about half the states and thousands of local governments that would resolve much of the litigation it faces.
Purdue has valued the settlement at $10 billion to $12 billion, which includes at least $3 billion in cash from the Sacklers, as well as money from future OxyContin sales and the development of addiction-treatment drugs.
Purdue’s proposed deal, however, still faces strong pushback from mostly Democratic state attorneys general from some two dozen states, including New York and Massachusetts. Adding other companies into the talks could further complicate negotiations.
Endo, Allergan and Mallinckrodt recently reached settlements cumulatively valued at $45 million to avoid a landmark opioid trial slated to start in late October that will test the claims of Ohio’s Cuyahoga and Summit counties. That trial has been selected to serve as a bellwether of some 2,000 of the opioid lawsuits centralized in federal court in Cleveland.
The U.S. district court judge overseeing the thousands of federal-court opioid cases, Dan Polster, has pushed both sides to settle the cases rather than waste time and money in protracted litigation. Finding a way to fully cap liability from cases brought by local and state governments in different courts around the country has been a challenge, however. Using Purdue’s chapter 11 case could provide a way to resolve claims on a near-complete basis.
A scenario in which companies use a bankruptcy proceeding to resolve legal liabilities, without filing for bankruptcy themselves, has some precedent.
Car makers that were sued along with Takata Corp. over defective air bags had an option to contribute money and settle the cases through Takata’s bankruptcy plan.
The settlement mechanism was optional on both sides, and only Honda Motor Co. had signed on as of February 2018, when Takata’s plan was confirmed. Unlike Purdue’s co-defendant drugmakers, the car makers were major creditors in Takata’s bankruptcy since they were owed money for funding the recall of millions of vehicles, as well as funding the bankruptcy case.
Walmart Inc. in 2014 obtained a release of liability over dangerous plastic gasoline cans as part of a $162 million settlement built into the chapter 11 plan of Blitz USA, which made the cans. The retailer had been sued for selling the Blitz cans.
So-called third-party releases, which clear a company that is not itself in bankruptcy of liability in exchange for some kind of value, are prohibited in some parts of the country. That isn’t the case in New York, where Purdue filed for bankruptcy, or Delaware, where Takata obtained protection.
Endo, Teva and Mallinckrodt each face significant debt in addition to the opioid lawsuits. Reaching a global resolution could help them avoid seeking bankruptcy protection or implementing broader restructurings.
https://www.marketscreener.com/ENDO-INTERNATIONAL-PLC-15914394/news/Drugmakers-Look-to-Use-Purdue-Pharma-s-Bankruptcy-to-Settle-Opioid-Suits-29315683/

NewLink -1.3% on Lumos merger

NewLink (NASDAQ:NLNK) and Lumos Pharma sign a definitive merger agreement that will result in Lumos becoming a wholly-owned subsidiary and NewLink taking on the Lumos name and new “LUMO” ticker.
Lumos shareholders will receive NLNK common stock shares in an exchange that will leave Lumos holders with a 50% stake in the resulting entity.
This merger is expected to provide the financial support necessary to expedite the clinical development of LUM-201 for PGHD, which could start its Phase 2b clinical trial in mid-2020.
The deal is expected to close in Q1 2020.
NLNK shares are down 1.3% after hours to $1.57.
https://seekingalpha.com/news/3502736-newlink-minus-1_3-percent-lumos-merger
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Catabasis Pharmaceuticals moves forward on PolarisDMD trial

Catabasis Pharmaceuticals (NASDAQ:CATB) says is has completed the enrollment for the Phase 3 PolarisDMD trial of edasalonexent in Duchenne muscular dystrophy.
Top-line results from the Phase 3 PolarisDMD trial are expected in Q4 of 2020 and the trial is anticipated to support an NDA filing in 2021.
Source: Press Release
https://seekingalpha.com/news/3502706-catabasis-pharmaceuticals-moves-forward-polarisdmd-trial

Geron +12.7% on fast-track designation

Geron (NASDAQ:GERNannounces the FDA granted fast-track designation to imetelstat for the treatment of adult patients with Intermediate-2 or High-risk myelofibrosis (MF) whose disease has relapsed after or is refractory to janus kinase (JAK) inhibitor treatment, or relapsed/refractory MF.
The designation includes patients with primary MF and MF developed after essential thrombocythemia.
The same patient population was studied in the IMbark Phase 2 clinical trial.
Geron intends to conduct an end of Phase 2 meeting with the FDA by the end of Q1 to see if there’s a regulatory path forward for imetelstat in relapsed/refractory MF.
GERN shares are up 12.7% after hours to $1.50.
https://seekingalpha.com/news/3502725-geron-plus-12_7-percent-fast-track-designation

Possible therapeutic target for slow healing of aged muscles

An age-related decline in recovery from muscle injury can be traced to a protein that suppresses the special ability of muscle stem cells to build new muscles, according to work from a team of current and former Carnegie biologists led by Chen-Ming Fan and published in Nature Metabolism.
Skeletal muscles have a tremendous capacity to make new muscles from special stem . These “blank” cells are not only good at making muscles but also at generating more of themselves, a process called self-renewal. But their amazing abilities diminish with age, resulting in poorer muscle regeneration from muscle trauma.
The research team—including Carnegie’s Liangji Li, Michelle Rozo, Sibiao Yue, Xiaobin Zheng, and Frederick Tan, as well as Christoph Lepper formerly of Carnegie now at the Ohio State University—figured out that a protein called GAS1 is the culprit for this .
“Encoded by the growth-arrest specific gene, the GAS1 protein lives up to its name, accelerating the functional decline of muscle stem cells,” explained lead author Li.
The protein is found in only a small number of young muscle stem cells, but is present in all aged muscle stem cells, they discovered. Tinkering with muscle stem cells to express GAS1 in the entire young stem cell population resulted in diminished regeneration. By contrast, removing GAS1 from aged muscle stem cells rejuvenated them to a youthful state that supported robust regeneration.
They also discovered that GAS1 inhibits another protein, a cell-surface receptor called RET, which they showed to be necessary for muscle stem cell renewal. The more GAS1 protein is present, the more RET’s function is reduced.
The inhibition of RET by GAS1 could be reversed by the third called GDNF, which binds to and activates RET. Indeed, when the researchers injected GDNF directly into the muscles of aged mice, muscle stem cell function and muscle regeneration were restored.
“With a rapidly aging population, issues like muscle deterioration are an increasing societal challenge,” said Fan. “Our work could reveal a potential pathway for therapeutic targeting to combat muscle degeneration in the elderly.”

Explore further
Why do aged muscles heal slowly?

More information: Muscle stem cell renewal suppressed by Gas1 can be reversed by GDNF in mice, Nature Metabolism (2019). DOI: 10.1038/s42255-019-0110-3 , https://nature.com/articles/s42255-019-0110-3

Esmo 2019 – mesothelioma trials contend with super-fast disease progression

A surprisingly successful study of Opdivo and Yervoy suggests that the enrolment of co-called hyperprogressors could have scuppered other trials.
If mesothelioma is too intractable for biopharma companies to devote much money to then at least academic co-operative groups can be relied on to pick up the slack. And one of these, Intergroupe Francophone de Cancerologie Thoracique, has scored an important result in its Maps-2 study, the Esmo congress heard today.
Though the trial was exploratory, it showed a “never-before seen” survival benefit with Opdivo plus Yervoy, said its presenting author, Professor Gerard Zalcman, of Hopital Bichat Claude Bernard. More importantly, perhaps, his findings hint at why so many mesothelioma studies fail: the influence on the overall result of patients he called “hyperprogressors”.
The question now is how hyperprogression has affected other trials, and whether patients whose mesothelioma progresses “classically” can derive a real benefit from immune and other late-line therapies. For instance, another trial profiled at Esmo today, Promise-meso, found no survival benefit whatsoever favouring Keytruda versus chemo.
The issue might have to be considered in ongoing mesothelioma studies, it was suggested, including Checkmate-743, one of the few large, industry-sponsored trials under way in this disease.
Survival map
In Maps-2, a trial in the second or third-line setting, Bristol-Myers Squibb’s Opdivo monotherapy resulted in median overall survival of 11.9 months, while a combo with Yervoy gave 15.9 months. Given the extremely aggressive nature of mesothelioma this was a sign of the two drugs being “truly active”, said Progessor Zalcman.
His group further analysed the 125 subjects enrolled and, using certain criteria calculating tumour growth rate, identified 11 as being hyperprogressors. The effect on median overall survival was striking: 23.1 months for subjects with disease control, 5.5 months for progressors, and only 2.6 months for hyperprogressors.
One reading of Maps-2, therefore, might be that it was lucky that only 11 of these extremely poor-prognosis patients were enrolled into it. Nevertheless, discussing the data, Institut Curie’s Dr Nicolas Girard called Maps-2 “clinically meaningful”, something that might bode well for Checkmate-743, though this tests Opdivo plus Yervoy first line.
He also suggested that the early part of the survival curves in Promise-meso, a second-line Keytruda trial run by the ETOP Foundation and unveiled at a late-breaker, was similar to those of Maps-2 hyperprogressors, and hinted that subjects in Promise-meso might in fact have had this aggressive disease.
A sadly similar pattern? Survival curves in Maps-2 (left; navy line is hyperprogressors) and Promise-meso (right). Source: discussant Dr Nicolas Girard & Esmo.
Despite bullishness from Esmo and from the lead investigator, Dr Sanjay Poppat of Royal Marsden Hospital, Promise-meso was a bust, showing no progression-free survival benefit, its primary endpoint, with a 6% increased risk for progression at any time for Keytruda subjects. Median OS was also numerically worse for Keytruda, at 10.7 versus 11.7 months for chemo.
There was no effect even adjusting for the 63% of control subjects who crossed over to Keytruda, and no identifiable subgroups derived a benefit from the Merck & Co drug. A separate Keytruda study, profiled at Asco 2017, had highlighted large differences in response between PD-L1-high patients and those with no expression.
Surprisingly, in Promise-meso there was a seemingly strong difference in overall remission rates – 22% for Keytruda versus 6% – but as most were of very short duration they did not translate into a survival benefit.
Guidelines?
While there are no universally accepted mesothelioma treatments second line or beyond, US NCCN guidelines already list Opdivo with or without Yervoy, as well as Keytruda, as possible options.
Meanwhile, another academic trial, run by the Swiss SAKK group, gave Pharmamar’s Zepsyre to 42 second/third-line subjects, and reported that this resulted in median OS and PFS of 11.1 and 4.1 months. Interestingly, in this case “slow” as well as “fast” progressing patients benefited from Zepsyre, Kantonsspital Graubünden’s Dr Yannis Metaxas told Esmo today.
Pharmamar’s focus with Zepsyre is small-cell lung cancer. Nevertheless, Dr Metaxas said his data warranted the testing of this project in mesothelioma in phase III.
https://www.evaluate.com/vantage/articles/events/conferences/esmo-2019-mesothelioma-trials-contend-super-fast-disease

Vir Biotech files for IPO to raise ~$134M

Vir Biotechnology (VIR) files for an initial public offering of 7.14M its shares and estimates the IPO price of $20.00-$22.00 per share.
Expects to grant greenshoe option for up to an additional 1.07M shares.
Sees proceeds of $134M, based on the midpoint of the price range, or $154.9M if underwriters excise the over-allotment option in full.
The company describes itself as a clinical-stage immunology company focused on combining immunologic insights with cutting-edge technologies to treat infectious diseases.
Intends to use proceeds to fund R&D of product candidates and development programs.
 The company’s current development pipeline consists of product candidates targeting hepatitis B virus, or HBV, influenza A, human immunodeficiency virus, or HIV, and tuberculosis, or TB.
VIR-2218, an HBV-targeting siRNA, is in an ongoing Phase 1/2 clinical trial and initial data have demonstrated substantial reduction of hepatitis B virus surface antigen, or HBsAg.  Based on initial data, VIR-2218 has been generally well-tolerated. Additionally, Vir has initiated a Phase 1/2 clinical trial for VIR-2482, a monoclonal antibody, or mAb, designed for the prevention of influenza A.
 In addition, current grants from the Bill & Melinda Gates Foundation will fund the manufacture and early clinical development of  two other products, VIR-1111, an HIV T cell vaccine, and VIR-2020, a TB T cell vaccine.
https://seekingalpha.com/news/3502681-vir-biotech-files-ipo-raise-134m