Celgene gets speedy review for thalassaemia drug luspatercept

It’s shaping up to be a landmark year for the community of patients with rare blood disorder beta thalassaemia. The first approval of a gene therapy in the EU has been followed swiftly by news that a Celgene drug could be approved in the US before year-end.

With the ink barely dry on the EMA’s approval notice for bluebird bio’s Zynteglo for transfusion-dependent thalassaemia (TDT), Celgene and partner Acceleron say they have secured an FDA priority review for luspatercept, a red blood cell-boosting drug designed to tackle the anaemia associated with the blood disorder.

The US regulator is due to deliver a verdict on luspatercept in thalassaemia-elated anaemia by 4 December, with a second verdict in anaemia linked to myelodysplastic syndrome (MDS) scheduled for next April in the standard review timeframe.

Luspatercept is an erythroid maturation agent that works by accelerating the maturation of red blood cells, and is also intended for seriously ill thalassaemia patients who require blood transfusions.

The BELIEVE study of the drug in TDT met its primary objective of a reduced need for transfusions compared to placebo, with a similar outcome for the MEDALIST trial in MDS, and prompted Celgene and Acceleron to predict sales of the drug could reach up to $2 billion.

If luspatercept can reach those heights it will be a big help to Celgene’s ambition of reducing its reliance on current cash cow product Revlimid (lenalidomide), which made $9.7 billion in sales last year but has generic competition looming in 2022.

It will also be a comfort to Bristol-Myers Squibb as its $74 billion takeover deal for Celgene rumbles towards the finishing post, despite some investor resistance.

Celgene also said that its marketing application in the EU has also been validated and the EMA review is now underway.

“The acceptance of the luspatercept filings and granting of the US priority review for beta-thalassaemia represent another important step in delivering this novel therapy to patients in need,” said Jay Backstrom, Celgene’s chief medical officer.

“We believe that luspatercept can play a critical role in treating the anaemia associated with these serious blood diseases, and with these milestones achieved we look forward to working closely with the agency to move this therapy toward approval.”

Celgene gets speedy review for thalassaemia drug luspatercept

Reata Gets Orphan Drug Designation for Kidney Disease Treatment

Reata Pharmaceuticals, Inc. (Nasdaq: RETA), a clinical-stage biopharmaceutical company, today announced the United States Food and Drug Administration (FDA) has granted orphan drug designation to bardoxolone methyl (bardoxolone) for the treatment of autosomal dominant polycystic kidney disease (ADPKD).

ADPKD is the most common inherited form of kidney disease affecting approximately 140,000 patients in the United States.  It is characterized by the development of pathologic fluid-filled cysts throughout the kidneys, which leads to organ enlargement and chronic kidney disease (CKD).  Despite standard of care treatment, approximately 50% of these patients will progress to end-stage kidney disease and require dialysis or a kidney transplant by 60 years of age.

“Obtaining orphan drug designation for bardoxolone for the treatment of ADPKD is an important milestone for Reata.  This is the third orphan drug designation obtained for bardoxolone in the United States for the treatment of diseases characterized by mitochondrial dysfunction and inflammation, and it is the second designation for the treatment of patients with rare forms of CKD,” said Warren Huff, Reata’s Chief Executive Officer and President.  “We believe that, if approved, bardoxolone may prove to be a meaningful new treatment option for patients with ADPKD.”

https://www.marketscreener.com/REATA-PHARMACEUTICALS-INC-28377265/news/Reata-Pharmaceuticals-Inc-Receives-Orphan-Drug-Designation-for-Bardoxolone-Methyl-for-the-Treatmen-28713072/

Takeda misses endpoints on Phase 3 amyloidosis trial

Takeda Pharmaceutical Company Limited (TSE: 4502/NYSE: TAK) today announced that the Phase 3 TOURMALINE-AL1 clinical trial in patients with relapsed or refractory systemic light-chain (AL) amyloidosis did not meet the first of two primary endpoints. Treatment with NINLARO^TM (ixazomib) in combination with dexamethasone did not demonstrate a significant improvement in overall hematologic response compared to physician’s choice of standard of care regimens. As a result of this analysis, Takeda has decided to discontinue the trial.

“While we are disappointed with this outcome, we aim to maximize our learnings from this trial and share findings with the community in hopes of helping to improve care for patients living with this devastating disease,” said Phil Rowlands, Ph.D., Head, Oncology Therapeutic Area Unit, Takeda. “This has been one of the largest studies ever conducted in systemic light-chain AL amyloidosis and we are proud to have led it. This study demonstrated our dedication to this rare and traditionally difficult-to-enroll patient population and we thank the patients and investigators for their engagement and participation. We remain optimistic about NINLARO and continue to investigate NINLARO in patient populations across the continuum of multiple myeloma care.”

An Independent Data Monitoring Committee (IDMC) did not raise any concerns about the safety profile of NINLARO in this setting.

https://www.marketscreener.com/TAKEDA-PHARMACEUTICAL-CO-6491073/news/Takeda-Pharmaceutical-Provides-Update-on-TOURMALINE-AL1-Phase-3-Trial-in-AL-Amyloidosis-28712485/

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