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Editing cells’ genomes with CRISPR-Cas9 might increase the risk that the altered cells, intended to treat disease, will trigger cancer, two studies published on Monday warn — a potential game-changer for the companies developing CRISPR-based therapies...scientists found that cells whose genomes are successfully edited by CRISPR-Cas9 have the potential to seed tumors inside a patient. That could make some CRISPR’d cells ticking time bombs...The CEO of CRISPR Therapeutics, Sam Kulkarni, told STAT the results are “plausible.” Although they likely apply to only one of the ways that CRISPR edits genomes (replacing disease-causing DNA with healthy versions) and not the other (just excising DNA), he said, “it’s something we need to pay attention to...We need to do the work and make sure edited cells returned to patients don’t become cancerous.”...Standard CRISPR-Cas9 works by cutting both strands of the DNA double helix. That injury causes a cell to activate a biochemical first-aid kit orchestrated by a gene called p53, which either mends the DNA break or makes the cell self-destruct...The flip side of p53 repairing CRISPR edits, or killing cells that accept the edits, is that cells that survive with the edits do so precisely because they have a dysfunctional p53 and therefore lack this fix-it-or-kill-it mechanism...The reason why that could be a problem is that p53 dysfunction can cause cancer...P53 mutations are responsible for nearly half of ovarian cancers; 43 percent of colorectal cancers; 38 percent of lung cancers; nearly one-third of pancreatic, stomach, and liver cancers; and one-quarter of breast cancers...

...Endo International has inked a deal to put 1,300 testosterone drug liability lawsuits to rest...The company disclosed a "master settlement agreement"...to resolve "all known" cases it faces. It will pay into a settlement fund, from which plaintiffs can release their claims...The deal doesn't include an admission of wrongdoing...Late last year, the company added $200 million to its legal reserves to cover costs in testosterone product liability litigation. The company reported in May that it faced about 1,300 testosterone cases. About 900 suits are in a nationwide multidistrict grouping against Endo and several other drugmakers...The plaintiffs alleged that Endo and other drugmakers overmarketed their testosterone drugs and ignored safety risks, leading to serious health complications...The company is among a group of drugmakers facing thousands of lawsuits alleging harm from testosterone replacement therapies. AbbVie faces about 4,600 lawsuits in the multidistrict litigation...while Eli Lilly faces about 500. All told, the multidistrict litigation includes about 7,700 testosterone liability lawsuits. Eli Lilly previously entered a memorandum of understanding about a potential settlement over lawsuits alleging harm from Axiron.

...FDA Commissioner Scott Gottlieb, MD, announced that the Center for Drug Evaluation and Research would be taking steps to modernize the organization and functions of the Office of New Drugs in order to address scientific and medical advances within the industry. The goal is to make the review process more integrated across science and regulatory expertise. Janet Woodcock, director of CDER, plans on elevating the role of FDA scientists and medical officers and providing these officers with more tools and support “to advance the clinical and regulatory principles that the FDA uses to evaluate new drugs for safety and efficacy.”...Other changes will include the development of guidance documents, giving review staff more time with sponsors, and getting sponsors involved earlier in the development process. Engaging disease specialists, academic researchers, regulatory partners at other agencies, and patient groups is also a goal of CDER.

The...Food and Drug Administration...sent warning letters to nine online networks operating a total of 53 websites to stop illegally marketing unapproved versions of opioid medications...The regulator said... it is taking additional steps with these warning letters by going right to the source of the illegal supply of unapproved and misbranded versions of opioid drugs, including tramadol and oxycodone...The internet is virtually awash in illegal narcotics...Drug dealers and rogue website operators are using the internet to fuel the opioid crisis...The regulator has requested responses from the nine companies within 10 working days, or they may be subject to product seizure or injunction.

A number of AbbVie products coming out of its North Chicago, Illinois, manufacturing facility have been tied to death complaints, including its mammoth blockbuster Humira, and the FDA says the drugmaker has not done enough to investigate those complaints...FDA inspectors found that AbbVie had received five complaints tied to deaths after taking Humira and Venclexta. While the drugmaker reported those, it didn't go back and compile historical data about death complaints tied to drugs coming from the same lots. It turns out those lots had been tied to another 8 to 11 complaints each...an AbbVie spokeswoman countered the FDA observation, saying the company “investigates all complaints where a death has occurred during the use of our products,” and that “written complaint procedures are in place to investigate, analyze and resolve complaints.”...The FDA also found AbbVie's procedures for handling death complaints for products made at the plant “inadequate.”...no document showed that AbbVie evaluated complaints to see if there were other ones for nearby lot numbers or different strengths, or that it examined the reserve sample...the agency also warned AbbVie for not examining reserve samples at least once a year for evidence of deterioration, and for its failure to investigate drug batches manufactured close to a problematic one.

The Swiss attorney general's office will not initiate criminal proceedings against Novartis over the $1.2 million the pharma paid a company controlled by President Donald Trump's personal lawyer Michael Cohen..."Following a detailed analysis, the OAG concluded that there was insufficient suspicion to justify opening criminal proceedings," the Office of the Attorney General of Switzerland wrote in an emailed statement...Not only was Cohen unable to deliver the sought-after advice, but recent revelations of the agreement led to accusations Novartis paid money to gain favorable treatment by the U.S. government...the deal was in place while Novartis was negotiating with the Centers for Medicare and Medicaid Services on reimbursement for its CAR-T cancer therapy Kymriah...

Kelly Davio, welcome to This Week in Managed Care from the Managed Markets News Network

Brexit uncertainty is forcing drugmakers in Britain to invest hundreds of millions of pounds to maintain the steady supply of medicines to patients, siphoning off money that could have gone to developing new treatments...Pharmaceutical companies are preparing for potential regulatory and trade hurdles after the U.K. leaves the European Union, expanding testing facilities, moving marketing authorizations and drafting contingency plans. Regulatory alignment between the EU and Britain makes sense to all sides, and if Britain remains part of Europe’s drug-approval system, a lot of the investment may prove to have been unnecessary, said Mike Thompson, chief executive of the Association of the British Pharmaceutical Industry...business leaders are urging Prime Minister Theresa May to finalize key Brexit decisions, many are already conducting costly preparations for a rocky break with the EU as the U.K. hurtles toward exiting the bloc in March 2019...The industry is concerned about possible delays in evaluating new drugs when the European Medicines Agency, the bloc’s regulator, moves to Amsterdam from London, he said. The agency is bracing for higher-than-anticipated staff departures due to a host of issues, including the effect of local labor laws on short-term contracts, EMA Executive Director Guido Rasi said in an interview...

Despite a decrease in the number of prescriptions for brand-name drugs going down, Part D spending and out-of-pocket costs both spiked up from 2011 to 2015, according to a new report from the Office of the Inspector General...The total reimbursement for all brand-name drugs in Part D rose by 77 percent from 2011 to 2015 even though there was a 17-percent drop in prescriptions for those drugs. Even after taking into account manufacturer rebates, reimbursement for Part D brand-name drugs still swelled by 62 percent during that time period,...the number of beneficiaries shouldering at least $2000 in out-of-pocket costs per year nearly doubled across the five-year time span and unit costs for brand-name drugs rose nearly 6 times faster than inflation...for small, rural or struggling hospitals whose razor thin margins are already the source of angst for c-suiters, watching drug spend totals steadily rise could force painful decisions like opting to not modernize EHRs or update equipment...

Kelly Davio, host, the Pharmacy Times News Network's Pharmacy Week in Review.