Stopping cancer before it develops

The body’s cells can sense when they’re about to become cancerous, and they can alert the immune system when they’ve become so damaged that they should be removed from the body. Question is, would it be possible to fend off cancer altogether by capitalizing on this process and improving it to ensure all precancerous cells are flushed from the body before they can make trouble?

Scientists at the University of Edinburgh have discovered two key immune molecules that could make that possibility a reality. They’re called toll-like receptors (TLRs) 2 and 10 and they can detect when cancer-causing genes, or oncogenes, have become active. They published their observations in the journal Science Advances.

When oncogenes become active they trigger a process called senescence, which prevents damaged cells from growing uncontrollably. But it’s not a fool-proof process.

“Damaged cancer-causing cells become senescent and are then killed by the body’s own immune system,” said Matthew Hoare, a scientist with Cancer Research UK Cambridge Institute, in a statement. “However, if the immune system does not destroy the senescent cell, the surrounding tissue can become inflamed, promoting cancer development.”

TLR2 and TLR10 are able to detect viruses and bacteria. By discovering their role in cancer detection, the University of Edinburgh scientists provided key insight into the molecular mechanisms that control senescence, which could lead to new strategies for fighting cancer, they believe.

Finding new ways to control senescence is a popular pursuit in biotech, particularly as it pertains to aging. Last year, for example, Cleara Biotech pulled in seed funding after it showed in mice that its modified peptide drug could restore fitness, hair growth and kidney function in mouse models of aging. The drug was designed to selectively eliminate senescent cells. Unity Biotech raised $85 million in an IPO last year to pursue a similar strategy.

But targeting senescence as a way to treat age-related diseases, including cancer, has proven challenging. Wistar Institute scientists discovered that promoting senescence does slow down tumor growth, but it also boosts the production of inflammatory cytokines and chemokines that can actually help the cancer to survive. They are working on methods for inhibiting cytokine and chemokine genes.

The University of Edinburgh team believes interfering with TLR2/10 signaling could be a strategy for helping the body to clear pre-cancerous cells. The cells rely on the signals to become inflamed and set off on the road to becoming cancerous, making the two toll-like receptors ideal drug targets, they argued in the new study.

https://www.fiercebiotech.com/research/stopping-cancer-before-it-develops

Mallinckrodt hit with new kickback charges same day as $15.4M settlement

Chafing under federal kickback charges tied to controversial opioid gel H.P. Acthar, Mallinckrodt appeared to be out of the woods with a settlement in the works. Turns out it was out of the frying pan and into the fire.

The DOJ filed new charges Wednesday against Mallinckrodt, which acquired Acthar-maker Questcor Pharma in 2014, accusing the company of funneling money through front funds to illegally subsidize Medicare copays and jack up the drug’s list price 85,000%. The newest charges filed in Pittsburgh federal court come the same day as the drugmaker and the federal government agreed in principle to a $15.4 million settlement on separate charges tied to two whistleblower kickback suits the DOJ joined in early May.

Mallinckrodt called the settlement “fair and reasonable” in a statement and vowed to fight the new federal charges.

“As we have said repeatedly, where we can resolve legacy legal matters in a reasonable and manageable way, we will do so,” Mark Casey, Mallinckrodt’s general counsel, said in a statement. “Unfortunately, that has not been possible to date regarding the allegations relating to Questcor’s charitable foundation activities, despite what we believe was lawful and appropriate activity.”

In their suit, federal prosecutors accused Mallinckrodt, through Questcor, of using three funds to illegally subsidize Medicare patient copays for Acthar while hiking the price of the drug from $50 to $32,000 per vial. In doing so, the DOJ alleged the company defrauded the federal government of millions of dollars through false Medicare claims and induced doctors to boost prescriptions of the drug.

“The subsidies it routed through these funds drove Acthar prescribing and was a proven method that negated concerns about the cost of the drug, allowing (Mallinckrodt) to continually raise its price,” prosecutors said.

The newest charges are only the latest knocks in Mallinckrodt’s troubled history with Acthar, with appeared to reach its nadir when the DOJ joined two whistleblower suits against the company in May.

Prosecutors said Questcor ran a “high-tiered strategy” to pay doctors to boost scripts for Acthar while using “dirty data” to mislead payers on the drug’s safety and usefulness. Whistleblowers said the company intimidated and fired employees who called its marketing strategy into question, using sham internal investigations to cover up illegal activity.

In its proposed settlement with the feds, Mallinckrodt did not admit any wrongdoing in the scheme, which allegedly took place prior to the Questcor’s acquisition. Mallinckrodt has argued that Acthar’s astronomical price increases took place prior to the Questcor buyout, although the company has instituted routine price hikes since acquiring the drug.

Those price hikes were the target of a separate federal probe that Mallinckrodt settled for $100 million in 2017 alleging Questcor bought and shelved an Acthar competitor in order to gouge the drug’s list price. The Federal Trade Commission investigation focused on Questcor’s 2013 acquisition of Synacthen Depot, a rival drug that regulators said was put aside in favor of development that didn’t compete with Acthar.

https://www.fiercepharma.com/pharma/mallinckrodt-hit-new-kickback-charges-one-day-after-15-5m-settlement-feds

Evolus up on strong Jeuveau ramp

Evolus (EOLS +15.9%) is up on 70% higher volume in reaction to the rapid enrollment in its Jeuveau Experience Treatment program. More than 3,000 provider accounts signed up in three weeks and 67% of patients switched from market leader BOTOX from Allergan (AGN -1.9%). Enrollment in J.E.T. will wind up on June 28.

On July 1, it will launch #NEWTOX NOW that will offer consumers $75 to help pay for treatment at participating practices. The company says both programs have it “on track” to achieve the #2 market position in the U.S. within 24 months of launch.

The FDA approved Jeuveau (prabotulinumtoxinA-xvfs) in May for the temporary improvement in the appearance of moderate to severe glabellar lines (frown lines) in adults.

https://seekingalpha.com/news/3469331-evolus-16-percent-strong-jeuveau-ramp

ReWalk Robotics soars after FDA clears exo-suit

ReWalk Robotics (NASDAQ:RWLK) rockets 113% in after-hours trading after the U.S. Food and Drug Administration clears the company’s ReStore soft exo-suit for sale to rehabilitation centers across the U.S.

The suit is intended for use in the treatment of stroke survivors with mobility challenges.

Launch price is $28,900 with leasing options.

https://seekingalpha.com/news/3469058-rewalk-robotics-soars-fda-clears-exo-suit

Insys Agrees to $225M Global Resolution of Criminal and Civil Probes

Opioid manufacturer Insys Therapeutics (NASDAQ: INSY) agreed to a global resolution to settle the government’s separate criminal and civil investigations, the Department of Justice announced today. As part of the criminal resolution, Insys will enter into a deferred prosecution agreement with the government, Insys’s operating subsidiary will plead guilty to five counts of mail fraud, and the company will pay a $2 million fine and $28 million in forfeiture. As part of the civil resolution, Insys agreed to pay $195 million to settle allegations that it violated the False Claims Act. Both the criminal and civil investigations stemmed from Insys’s payment of kickbacks and other unlawful marketing practices in connection with the marketing of Subsys. Insys’s drug Subsys is a sublingual fentanyl spray, a powerful, but highly addictive, opioid painkiller. In 2012, Subsys was approved by the Food and Drug Administration for the treatment of persistent breakthrough pain in adult cancer patients who are already receiving, and tolerant to, around-the-clock opioid therapy.

Today, the U.S. Attorney’s Office for the District of Massachusetts filed an Information charging Insys and its operating subsidiary with five counts of mail fraud. According to the charging document, from August 2012 to June 2015, Insys began using “speaker programs” purportedly to increase brand awareness of Subsys through peer-to-peer educational lunches and dinners. However, the programs were actually used as a vehicle to pay bribes and kickbacks to targeted practitioners in exchange for increased Subsys prescriptions to patients and for increased dosage of those prescriptions. One practitioner targeted by Insys was a physician’s assistant who practiced with a pain clinic in Somersworth, New Hampshire. During the first year that Subsys was on the market, the physician’s assistant did not write any Subsys prescriptions for his patients. In May 2013, the physician’s assistant joined Insys’s sham speaker program knowing that it was a way to receive kickbacks for writing Subsys prescriptions. After joining the sham speaker program, the physician’s assistant wrote approximately 672 Subsys prescriptions for his patients – many of which were medically unnecessary – and in turn, received $44,000 in kickbacks from Insys.

As part of the criminal resolution, Insys agreed to a detailed statement of facts outlining its criminal conduct with respect to the illegal marketing of Subsys. Insys will enter into a five-year deferred prosecution agreement with the government, while Insys’s operating subsidiary will plead guilty to five counts of mail fraud pursuant to the plea agreement that will be filed in the District of Massachusetts. According to the terms of the criminal resolution, Insys will pay a criminal fine of $2 million and forfeiture of $28 million. The Court has not yet scheduled the plea hearing. Last month, five former Insys executives were convicted after trial of racketeering conspiracy in connection with the marketing of Subsys. In total, eight company executives have now been convicted in Boston for crimes relating to the illegal marketing of Subsys.

In April 2018, the United States intervened in five qui tam lawsuits accusing Insys of violating the civil False Claims Act. In its Complaint, the United States alleged that Insys, headquartered in Arizona, paid kickbacks to induce physicians and nurse practitioners to prescribe Subsys for their patients. In addition to payments for sham speaker program speeches, the kickbacks also allegedly took the form of jobs for the prescribers’ relatives and friends, and lavish meals and entertainment. The United States also alleged that Insys improperly encouraged physicians to prescribe Subsys for patients who did not have cancer, and lied to insurers about patients’ diagnoses in order to obtain reimbursement for Subsys prescriptions that had been written for Medicare and TRICARE beneficiaries.

https://www.streetinsider.com/Corporate+News/Insys+Therapeutics+%28INSY%29+Agrees+to+Enter+%24225+Million+Global+Resolution+of+Criminal+and+Civil+Investigations/15584231.html

Wells Fargo: Medtronic An Accelerating Growth Story Trading At A Discount

Medtronic PLC MDT 2.31% has earned a bullish review from Wells Fargo Securities, which premised its optimistic outlook on the company’s growth prospects.

The Analyst

Larry Biegelsen upgraded Medtronic from Market Perform to Outperform and increased the price target from $100 to $110.

The Thesis

Medtronic’s late-stage pipeline will likely drive a growth acceleration beginning in May 2020 and extending into fiscal 2021, Biegelsen said in a Tuesday note. (See his track record here.)

The company has managed Street expectations over the past year, exceeding EPS estimates by an average of 6-7 cents over the past four quarters, the analyst said.

Medtronic shares are trading at a 20-percent discount to large-cap medtech peers, and the discount could close as the pipeline materializes and top-line growth accelerates, he said.

Wells Fargo raised its 2020-2024 revenues estimates for Medtronic by $22 million, $181 million, $342 million, $483 million and $554 million, respectively, on the basis of the following:

• Greater market share capture from Micra AV.
• The inclusion of a surgical robot to the firm’s model, with a potential launch in 2020.
• The adding back of renal denervation estimates to the model.

Biegelsen raised 2020-2024 EPS estimates by a penny, 3 cents, 6 cents, 10 cents and 6 cents, respectively.

Wells Fargo sees Medtronic as an accelerating growth story trading at a discount to peers, the analyst said. The firm estimates an acceleration in organic growth from 2.8 percent in the first quarter to 4.4 percent in the fourth quarter and from 3.8 percent in 2020 to 4.7 percent in 2021, he said.

The firm sees the following as drivers of this acceleration:

• The Micro AV leadless pacemaker.
• The surgical robotic platform.
• Reveal Linq 2.0.
• The 780G diabetes pump.
• The next-gen Interstim device.

https://www.benzinga.com/analyst-ratings/analyst-color/19/06/13865765/wells-fargo-medtronic-an-accelerating-growth-story-trading-at-a-discount

InflaRx Hit As Skin Inflammation Drug Flunks Midstage Trial

Shares of the thinly traded, micro-cap biotech Inflarx NV IFRX 91.87% were losing 90 percent of their value Wednesday following a failed clinical trial. ChemoCentryx Inc CCXI 19.22%, which has a rival drug in its pipeline, traded down in sympathy

What Happened

InflaRx announced top-line results from the Phase 2b study SHINE, which showed that IFX-1, its pipeline candidate for treating moderate-to-severe Hidradenitis suppurativa, or HS, did not meet the primary endpoint of demonstrating a statistically significant dose-dependent effect on the HS Clinical Response, or HiSCR rate, at week 16.

The HiSCR rate was 51.5 percent for the treatment arm compared to 47.1 percent for the placebo arm.

HS is a chronic inflammatory skin disease with limited treatment options.

IFX-1, InflaRx’s lead compound, is a first-in-class anti-human complement factor C5a monoclonal antibody being evaluated for multiple indications. The HS indication is in the most advanced stage of clinical development.

ChemoCentryx Trades Down

ChemoCentryx, a small-cap biotech, is moving in sympathy with InflaRx. The move in the stock is in reaction to the read-through from the InflaRx trial setback, JPMorgan analyst Anupam Rama told Benzinga.

ChemoCentryx’ CCX168 is being tested for HS in a Phase 2b trial.

https://www.benzinga.com/general/biotech/19/06/13867945/inflarx-shares-slammed-as-skin-inflammation-drug-flunks-midstage-trial-chemocentryx-moves-in-symp