Orchard to file gene therapy in life-threatening rare disease next year

Orchard Therapeutics has said it plans to file for approval for a gene therapy for the life-threatening rare disease metachromatic leukodystrophy (MLD) in Europe, after publishing new data.

The biotech said it planned to file data from its OTL-200 gene therapy with regulators early next year in Europe after results from a late-stage trial showed clinical benefit on cognitive and motor function. A filing with the FDA is planned for around a year later, the company said.

Orchard bought OTL-200 from GSK in April 2018 from GlaxoSmithKline along with a portfolio of other rare disease drugs, with the big pharma taking a 19.9% equity stake.

OTL-200 is an ex vivo, autologous, hematopoietic stem cell-based gene therapy – meaning it is based on cells derived from a patient’s own body.

It originated from a collaboration between GSK and Fondazione Telethon and Ospedale San Raffaele, acting through their joint San Raffaele-Telethon Institute for Gene Therapy in Milan, initiated in 2010.

Orchard also markets Strimvelis, a gene therapy for the immune deficiency caused by the rare disease adenosine deaminase deficiency (ADA-SCID) – commonly referred to as ‘bubble boy syndrome’ – developed through the same collaboration.

Latest data for OTL-200 came from an integrated analysis of 29 early-onset MLD patients – 16 late infantile and 13 early juvenile – treated with gene therapy and analysed to assess efficacy and safety of OTL-200.

At the last follow-up, 26 patients are alive and have completed up to 7.5 years of follow-up (median 3.2 years) post-gene therapy. The three patient deaths were deemed unrelated to treatment with OTL-200.

Results were compared with those from an age-matched natural history cohort of 31 untreated MLD patients.

Affecting one in every 100,000 live births, MLD is caused by a mutation in the arylsulfatase-A (ARSA) gene that results in accumulations of sulfatide in the brain and other organs including liver, the gallbladder, kidneys, and/or spleen.

Over time the nervous system is damaged and patients with MLD experience neurological problems such as motor, behavioural and cognitive regression, severe spasticity and seizures, and difficulties talking, swallowing and seeing.

In its late infantile form mortality at five years from onset is estimated at 50% and 44% at 10 years for juvenile patients.

A bridging study assessing a cryopreserved formulation of OTL-200 in patients with pre-symptomatic MLD is under way, with data expected at the end of 2019.

Orchard to file gene therapy in life-threatening rare disease next year

Boehringer in deal with India’s Lupin, as pharma awaits key Amgen data

Boehringer Ingelheim has signed a deal with India’s Lupin to develop and market a potential cancer drug targeting tumours driven by the KRAS mutation.

Under the deal Lupin will receive an upfront payment of $20 million and potential additional payments for achieving clinical, regulatory and commercial milestones for a total deal value of more than $700 million.

Lupin will be entitled to receive double-digit royalties on the sales of the product.

Occurring in around one in 7 cancers, KRAS has become a priority for big pharma after Amgen’s AMG-510 showed activity against tumours with a subtype known as KRAS G12C in a phase 1 trial involving solid tumours at ASCO in June.

This was the first time that a KRAS-targeting drug had produced a response in the clinic and updated results from the trial are expected at the International Association for the Study of Lung Cancer (IASLC) conference this weekend.

In the meantime several other pharmas are focusing on KRAS research, hoping to follow Amgen’s example.

Boehringer Ingelheim has been busy building a pipeline of KRAS drugs and this latest deal adds an MEK inhibitor, LNP3794, developed by Lupin to the mix.

Lupin is best known for generics and over-the-counter drugs but has also started to focus on developing its own novel drugs.

The partnership with Lupin will aim to develop LNP3794 in combination with one of BI’s KRAS inhibitors for patients with gastrointestinal and lung cancers, harbouring a broad range of oncogenic KRAS mutations.

The collaboration will also investigate sub-populations that may need more effective therapies.

KRAS is much more common in certain types of cancers: it occurs in more than 90% of pancreatic cancers, a disease badly served by approved therapies, and poor survival outcomes.

It also occurs in more than 40% of colorectal cancers and more than 30% of lung adenocarcinomas.

Preclinical data has shown that the combination of BI’s novel KRAS inhibitors with MEK inhibitors results in increased anti-tumour activity based on their complementary mechanisms of action in keeping KRAS-driven cancers in check.

Novartis is also looking at KRAS with San Diego-based Mirati in a tie-up announced soon after ASCO.

BI signs KRAS deal with India’s Lupin, as pharma awaits key Amgen data

Immunic up 26% after hours on encouraging IMU-838 data

Thinly traded micro cap Immunic (NASDAQ:IMUX) is up 26% after hours on modest volume in apparent response to a pre-planned interim analysis of its Phase 2 CALDOSE-1 study evaluating IMU-838 in patients with moderate-to-severe ulcerative colitis.

The data showed activity at the lowest dose (10 mg) and tolerability at the highest dose (45 mg). The trial will continue with all three dosing arms (30 mg is the other).

The expansion of the potentially effective dose range will increase the target enrollment to ~240 from 195, expected to be completed in H2 2020. Topline data should be available in Q1 2021.

The company says IMU-838 is an orally available, next-generation immune modulator that dampens the immune response by inhibiting an enzyme called dihydroorotate dehydrogenase (DHODH) that plays a key role in intracellular metabolism of activated immune cells.

https://seekingalpha.com/news/3497531-immunic-26-percent-hours-encouraging-imuminus-838-data

Dozens of Texas hospitals sue drug industry players over opioid epidemic

Dozens of hospitals in Texas filed a lawsuit accusing pharmaceutical companies and pharmacy giants of fueling the opioid crisis in the state, Fox 4 reported.

Hospitals and government officials accuse the companies of marketing opioids without being fully transparent about the risks.

The hospitals are seeking billions of dollars in damages to help pay for treatment required for the growing number of patients addicted to opioids.

The lawsuit, filed on Sept. 3, claims the number of opioid-related deaths tripled in Texas between 1999 and 2015, with 14,171 opioid-related deaths reported during that period.

The defendants, which include Walgreens and CVS Health, have 30 days to file an answer once they’re served with the lawsuit.

https://www.beckershospitalreview.com/pharmacy/dozens-of-texas-hospitals-sue-drug-industry-players-over-opioid-epidemic.html

Judge approves $55M sale of Hahnemann residency programs

A bankruptcy court judge ruled Sept. 5 that a group of six health systems in the Philadelphia area can buy Hahnemann University Hospital’s residency program for $55 million, according to The Philadelphia Inquirer. 

U.S. Bankruptcy Judge Kevin Gross ruled in favor of Philadelphia-based Hahnemann, which says the money will help the hospital pay its creditors.

The ruling came despite objection from CMS, which funds the residency programs. Lawyers from CMS argued the sale was against the law and Hahnemann’s Medicare agreement terminates upon closure and can’t be transferred to other institutions.

The federal government has one week to appeal the decision.

The coalition of six health systems — Philadelphia-based Jefferson Health, Einstein Healthcare Network and Temple University Health System, as well as Bryn Mawr, Pa.-based Main Line Health, Camden, N.J.-based Cooper University Health Care and Wilmington, Del.-based Christiana Care Health System —  won a bid to buy Hahnemann’s more than 550 residency slots for $55 million in August.

Hahnemann filed for bankruptcy in June and will close Sept. 6.

https://www.beckershospitalreview.com/hospital-transactions-and-valuation/judge-approves-55m-sale-of-hahnemann-residency-programs.html

Stopping progression of tissue injury after button battery ingestion

Button battery injuries in children have been increasingly severe–resulting in devastating injuries and even death. Button batteries damage esophageal tissue through isothermic hydrolysis reactions, resulting in alkaline caustic injury, which leads to tissue necrosis. Prompt removal of the battery is critical to minimizing damage. However, when children swallow a button battery, the injury can progress even after it is removed.

In a recent study from surgeon-researchers at Nationwide Children’s Hospital, esophageal irrigation in the operating suite with dilute sterile vinegar, 0.25% acetic acid, after button battery removal was safe and improved mucosal appearance. Household cooking vinegar is typically a 5% concentration.

“Progression of esophageal tissue damage after removal is a hallmark of button battery injury,” says Kris Jatana, MD, director of Pediatric Otolaryngology Quality Improvement at Nationwide Children’s and lead author of the study publication. “Complications may be delayed up to 9 days for tracheoesophageal fistulas and up to 28 days for aortoesophageal fistulas.”

The study, published in The Laryngoscope, followed data from six consecutive patients aged 19 months to 10 years who had a 3V lithium button battery lodged in the esophagus for 2 to 18 hours. Surgeons irrigated the injury site with sterile 0.25% acetic acid after removal.

“When we looked at the tissue in the OR, we could see that it was visually improved after the irrigation,” says Dr. Jatana, who is also an associate professor in the Department of Otolaryngology – Head and Neck Surgery at The Ohio State University. “And none of these patients showed immediate or delayed esophageal complications.”

The National Capital Poison Center Button Battery Guidelines currently recommends this new irrigation with 0.25% acetic acid during button battery removal. This is the first case series published in pediatric patients, using this initial concept that began at Nationwide Children’s. It is now being performed around the world after esophageal button battery removal.

“This study highlights the importance of rapid endoscopic removal and the need for additional strategies to neutralize the injury site. Rapid neutralization of esophageal tissue pH as soon as possible after button battery removal may prevent the continued tissue injury associated with a prolonged alkaline environment and reduce long-term complications,” concludes Dr. Jatana, who is also a Co-Chair of the National Button Battery Task Force, affiliated with the American Academy of Pediatrics and American Broncho-Esophagological Association. “This is something that all surgeons can consider to improve outcomes after esophageal button battery injury.”

https://www.eurekalert.org/pub_releases/2019-09/nch-spo090519.php

Risk for people coming off chronic opioid prescriptions

With a huge push to reduce opioid prescribing, little is known about the real-world benefits or risks to patients.

A recent study published in the Journal of General Internal Medicine found an alarming outcome: Patients coming off opioids for pain were three times more likely to die of an overdose in the years that followed.

“We are worried by these results, because they suggest that the policy recommendations intended to make opioid prescribing safer are not working as intended,” said lead author Jocelyn James, assistant professor of general internal medicine at the University of Washington School of Medicine. “We have to make sure we develop systems to protect patients.”

Physicians had already begun to reduce opioid prescribing by 2016, when the CDC issued its first guideline on opioid prescribing. That trend accelerated after 2016.

While reduced prescribing may well be intended to improve patient safety, little is known about the real world benefits or risks of this sea change in opioid prescribing.

The study looked at a cohort of 572 patients with chronic pain enrolled in an opioid registry. Chronic opioid therapy was discontinued in 344 patients and 187 continued to visit a primary care clinic. During the study period, 119 registry patients died (20.8%); 21 patients died of a definitive or possible overdose – 17 were discontinued patients and four were patients being seen at a clinic.

As the researchers concluded: “Discontinuing chronic opioid therapy was associated with increased risk of death.”

Researchers said that improved clinical strategies, including multimodal pain management and treatment of opioid-use disorder, may be needed for this high-risk group.

At the time of this study, state rules did not allow medication treatment of opioid-use disorder in the primary care setting, said co-author Joseph Merrill, professor of general internal medicine at the University of Washington School of Medicine.

But after those rules changed, he said the addiction clinic at Harborview has developed a strong program to provide medication treatment for opioid-use disorder, including those who develop problems related to prescription pain medication.

“We hope these findings encourage others who prescribe opioids to do the same,” Merrill said.

Researchers said the UW Medicine study is the third study published this year to look at the risks of stopping opioids:

• A study published in the Journal of Substance Abuse Treatment found that among patients at high dose who stopped opioids, almost half had their doses reduced to 0 in a single day and many wound up in emergency departments.
• A New York study in the Journal of General Internal Medicine found that ending opioid prescriptions was often followed by an end to the care relationship.
• This spring the United States Food and Drug Administration issued a warning that suddenly stopping opioids can present a risk to patients.

https://www.eurekalert.org/pub_releases/2019-09/uowh-rfa090519.php