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Monday, September 30, 2019

Spending Variation ‘Substantial’ Between Providers in Same Specialty

A report indicates that variation among providers affects spending on “medications, labs and radiology.”

Behavioral factors by doctors contribute to significant cost variations, even among the same type of patients, according to an Illumicare report released Tuesday morning.
The analysis of 15 sub-specialty groups with the largest cost variations found that the most significant factor was “what type of spender a patient’s provider is,” with cardiology and OB/GYN specialists leading the way.
Between the 25th and 75th percentiles, there was a $5,438 variation among pediatric hematology-oncologists, a difference of $3,885 among OB/GYN orders of cesarean sections without complications or comorbidities, and almost a $3,000 difference among OB/GYN orders on vaginal delivery without complicating diagnosis.
G.T. LaBorde, CEO of IllumiCare, told HealthLeaders that the purpose of the report was to communicate to the broader healthcare market about how much variation exists among doctors taking care of the same group of patients.
“What frustrates so many [healthcare executives] is when they say to a cardiologist, ‘Your patients are staying 1.2 days longer,'” LaBorde said. “Telling the cardiologist that isn’t insightful to them, it doesn’t help them understand the behavior that might be aberrant that leads to a longer length of stay. It only becomes actionable if [CFOs] can get so discreet that they can say, ‘Well, in this scenario, you’re the only provider that uses this drug,’ or ‘You tend to order this lab test more frequently than your peers.'”
“If a CFO can get that discreet, they can get to a point where they start changing behaviors which can change outcomes.”

The Illumicare report states that it should be “alarming” for health systems to see such substantial cost variations arising from standard medical procedures, which reinforces the need to address the issue with providers.
Ordering medications, lab tests and radiological exams were highlighted as the primary pain points for cost variations within a sub-specialty.
In one example from the report, cardiologists at three separate hospitals were analyzed on the basis of medications ordered for patients.
Thirty-three medications were ordered by cardiologists at all three hospitals, whereas 54 medications were ordered by cardiologists at only one hospital.

Servier acquires lymphoma treatment PIXUVRI from CTI BioPharma

Servier, an independent international pharmaceutical company, today announced the acquisition of PIXUVRI® from CTI BioPharma. PIXUVRI is a treatment for adult patients with multiply relapsed or refractory aggressive non-Hodgkin B-cell lymphoma. Servier and CTI Biopharma completed an Asset Purchase Agreement which transferred worldwide rights of PIXUVRI to Servier. Servier commercialized PIXUVRI globally, in all countries where the drug was approved under an exclusive license from CTI BioPharma.
“The acquisition of PIXUVRI is an important step towards Servier’s long-term strategy to become a key player in oncology. Within oncology, one of our key focuses is hematology, and we now have two medicines that are marketed globally alongside a strong and innovative pipeline of drug candidates which includes CAR-T therapies,” said Claude Bertrand, Executive VP, Global Head of R&D at Servier. “As part of our strategy, we are committed to invest 50% of our R&D budget in oncology.”–29317108/

AstraZeneca Update on US regulatory review of PT010 in COPD

AstraZeneca today announced that the US Food and Drug Administration (FDA) has issued a complete response letter regarding the New Drug Application (NDA) for PT010 (budesonide/glycopyrronium/formoterol fumarate), an inhaled triple-combination therapy and potential new medicine for patients with chronic obstructive pulmonary disease (COPD).
The NDA submitted to the FDA by AstraZeneca included data from the Phase III trial KRONOS. The Company will now work closely with the FDA regarding next steps, including submitting for review recent results from the second positive Phase III trial, ETHOS, which was not completed at the time the NDA was submitted.
PT010 was approved in Japan ( in June 2019 as Breztri Aerosphere, a triple-combination therapy to relieve symptoms of COPD. PT010 is under regulatory review in China where it has been granted priority review by the National Medical Products Administration, and is also under regulatory review in the EU.

Three pharmacies now pulling Zantac over FDA alert

Three major pharmacies are now pulling Sanofi’s (NASDAQ:SNY) heartburn medication Zantac off the shelves, after an FDA alert about potential low levels of a probable human carcinogen.
CVS (NYSE:CVS) had previously pulled the drug, and Walgreens (NASDAQ:WBA) and Rite Aid (NYSE:RAD) have joined in by removing the medication.
The FDA has said some ranitidine medicines including Zantac contain NDMA at low levels (levels that barely exceed amounts you might expected to find in common foods, it says).
There’s no recall of the medication, but all three pharmacies are accepting it for returns.

Bristol-Myers Squibb (BMY) Presents At ESMO Congress 2019 – Slideshow

The following slide deck was published by Bristol-Myers Squibb Company in conjunction with this event.
ESMO 2019

Dementia Outcomes Improved With Supportive Care

Dementia patients’ quality of life improved over 12 months with team-based telephone and Internet support, a survey of dementia caregivers in the Care Ecosystem randomized trial showed.
Care delivered by a trained, unlicensed care team navigator and managed by an advanced-practice nurse, a social worker, and a pharmacist improved multiple facets of care, reported Katherine Possin, PhD, of the University of California San Francisco, and coauthors in JAMA Internal Medicine.
These included measures of patient quality of life, emergency department visits, caregiver depression, and caregiver burden.
“This study demonstrates that effective phone-based dementia care that addresses the needs of the person with dementia and the caregiver can be provided from a hub across large geographic areas, irrespective of the patients’ healthcare system affiliations,” Possin told MedPage Today.
“The Care Ecosystem addresses gaps in our healthcare system around dementia,” she continued. “While the Care Ecosystem won’t cure dementia, it changes the experience of dementia for both the patients and the caregivers, so that they may live as well as possible.”
A model like the Care Ecosystem can expand the reach of the dementia specialist workforce, Possin added. “We work at an academic medical center, where we have a lot of dementia specialists, and we are able to provide high-quality dementia care,” she noted. “But many people living with dementia in this country have limited or no access to dementia specialists because of where they live or because it is hard for them to travel to appointments.”
Earlier data from the Care Ecosystem research group showed that caregiver and dementia health were intertwined: dementia patients were nearly twice as likely to use an emergency department if their caregiver had depression, for example.
“Dementia is a public health challenge, a family disease, and a major strain on our healthcare system,” observed Jennifer Tjia, MD, MSCE, of the University of Massachusetts in Worcester, in an accompanying editorial. “Possin and colleagues have provided evidence that achieving the goals of the triple aim of improving care, health outcomes, and reducing cost can be met by providing dementia training to clinically supervised, unlicensed care team navigators in a scalable way.”
The single-blind, pragmatic Care Ecosystem trial was conducted in California, Nebraska, and Iowa in urban (San Francisco and Omaha) and rural settings. It randomized 780 dyads of dementia patients and caregivers — 512 to the Care Ecosystem intervention and 268 to usual care — from March 2015 to February 2017, tracking each dyad for 1 year.
All eligible patients had a dementia diagnosis from a treating provider and were enrolled in or eligible for Medicare or Medicaid. About half (49.8%) of patients had mild dementia; 28.7% had dementia, and 21.5% had severe dementia. Participants were informed of their randomization result and continued to receive services from other healthcare professionals throughout the study.
In the Care Ecosystem group, patients and caregivers received telephone-based, collaborative care from a team of dementia specialists. The team navigator was an unlicensed, trained guide who served as the primary point of contact for patients and caregivers under nurse supervision. Navigators called dyads approximately monthly; the number of telephone calls averaged 15.3 per dyad over 12 months. The nurse, social worker, and pharmacist were available for situations beyond the navigator’s scope, including safety concerns, behavioral symptoms, or complex legal and financial circumstances.
In the usual care group, participants were offered contact information for the Family Caregiver Alliance, the Alzheimer’s Association, and Area Agencies on Aging. They also were sent quarterly newsletters with general dementia-related articles and word games.
All outcomes were based on caregivers’ answers to telephone survey questions. The primary outcome measure was the Quality of Life in Alzheimer’s Disease (QOL-AD) score, which rated 13 aspects of patient quality of life — such as physical health, energy level, mood, memory, ability to do things for fun, and family relationships — on a four-point scale of poor, fair, good, or excellent.
For the primary outcome, caregivers reported that the Care Ecosystem improved patient quality of life (β 0.53, 95% CI 0.25-1.30; P=0.04). In secondary outcomes, the Care Ecosystem program was shown to do the following:
  • Reduce emergency department visits (β −0.14, 95% CI −0.29 to −0.01; P=0.04)
  • Decrease caregiver depression (β −1.14, 95% CI −2.15 to −0.13; P=0.03)
  • Lessen caregiver burden (β −1.90, 95% CI −3.89 to −0.08; P=0.046)
The effects of the Care Ecosystem on ambulance use and hospitalization were not significant, and the number needed to treat to prevent a single emergency department visit was 5. Comparing hospital and emergency services in the intervention group against expected use based on usual care data, the researchers calculated that the Care Ecosystem prevented 120 emergency department visits, 16 ambulance use events, and 13 hospitalizations over 12 months, providing an average cost savings of $600 per patient in these three services.
The study had several limitations, the researchers noted. Dyads were aware of their randomization, and the sample selected likely had fewer unmet needs than patients and caregivers in other populations. Economic outcomes were reported only for 12 months and were based on survey results.
“For many families, supportive dementia care such as the Care Ecosystem can change the experience of living with dementia,” Possin said. Supportive care can reduce stress and burdens on caregivers, she noted: “They are not alone, and can actually plan ahead for challenges that are coming, rather than feeling they are in a constant state of crisis.”
Last Updated September 30, 2019
This project was funded by the Department of Health and Human Services, Centers for Medicare & Medicaid Services, Global Brain Health Institute, National Institute on Aging, and National Institute on Neurological Disorders and Stroke.
The researchers reported relationships with the Centers for Medicare & Medicaid Services, National Institute on Aging, National Institute of Neurological Disorders and Stroke, Global Brain Health Institute, National Center for Advancing Translational Sciences, National Palliative Care Research Center, the John A. Hartford Foundation, the West Foundation, the Patient Centered Outcomes Research Institute, the American Academy of Hospice and Palliative Medicine, and Cornell University, as well as receiving UCSF grants.
The editorialist reported grants from the National Institutes of Health and the Cambia Health Foundation, personal fees from the Donaghue Foundation, and personal fees and nonfinancial support from CVS Health outside the study.

Cancer immunotherapy boom showing no sign of slowdown

  • Nearly twice as many cancer immunotherapies are now in development as were in testing two years ago, according to a new report from the Cancer Research Institute that highlights how the field has rapidly become a top target of drugmaker investment.
  • Just under 3,900 active drugs are now under preclinical or clinical study, up 91% from 2017, researchers from CRI found. A large portion of that growth came in cell therapy, with 797 new agents added to the industry’s pipeline over the past two years.
  • While roughly two-thirds of the drug candidates tracked by the institute are in preclinical stages, the number of immunotherapies in clinical testing grew significantly, too.
Cancer immunotherapy appears an investment that drugmakers can’t pass up.
The industry’s pipeline continues to expand rapidly, with more than 5,000 active immuno-oncology studies listed in the federal database
Researchers at CRI counted 60% more organizations, including academic and research groups, were actively conducting testing of cancer immunotherapies in 2019 than in 2017, according to data published Friday in Nature Drug Discovery.
“This tremendous investment and commitment from different sectors have laid the foundation for 31 approvals by the FDA for IO drugs in the past 2 years,” the report’s authors wrote.
For companies like Merck & Co., Bristol-Myers Squibb and Roche, cancer immunotherapies are now a crucial part of revenue growth. But others, like Novartis, Celgene, Amgen and Eli Lilly, have expanded their pipelines in hopes of gaining ground on the field’s initial leaders.
Much of that research, however, focuses on similar biological pathways. There are more than 190 CD19-targeted immunotherapies in some form of testing, for example, as well as roughly 200 PD-1 and PD-L1 inhibitors.
Such overlap has raised concerns about duplicative efforts, as companies chase already proven drug classes.
Encouragingly, however, CRI found that 205 more targets were being studied in 2019 than in 2017, bringing the total ot 468 active targets. Some of the more common targets without an approved treatment include NY-ESO-1 and STAT3.
CRI’s numbers for clinical immunotherapy candidates are higher than the nearly 450 counted this year by IQVIA, a research group, although differences in definitions could explain the gap.
In its May 2019 report, IQVIA noted growth in the overall number of cancer drugs in development and found more than 212,000 Americans were treated with PD-1 or PD-L1 drugs last year, up nearly 100-fold from 2014.

What’s in your CBD? Buyer beware

CBD (or cannabidiol) products, containing a compound found in marijuana, have skyrocketed in popularity and seem to be for sale everywhere, from grocery stores, to coffee shops and gas stations.
CBD itself does not get you high, but advocates say it can help with anything from muscle aches to anxiety. It’s forecast to become a $22 billion industry by 2024.
But without wide federal oversight, there is no way of really knowing what’s inside CBD.
So, we decided to find out.
CBS News partnered with Mile High Labs, in Colorado, to test nine CBD oil samples purchased from around the country.
Test results from nine samples of cannabidiol (CBD) products show some surprising results that could produce serious health side-effects. CBS News
It took two days for senior lab associate Joshua Cogell to test our nine samples, checking for CBD and for THC (the ingredient in marijuana that gives a high), and also for dangerous impurities, like pesticides and heavy metals.
“We test for four different heavy metals: mercury, arsenic, cadmium and lead,” said Cogell.
“They all sound bad,” said correspondent Barry Petersen.
“They are very, yes, things you do not want in your body.”
The CBD craze took off when President Trump signed the Farm Bill last December. The bill allows farmers to legally grow hemp, the source of CBD. It is a member of the marijuana plant family, but it produces only trace amounts of THC. Under the bill, the government allows less than 0.3% THC in CBD products.
Here’s what Mile High found in our samples:
  • None had pesticides or heavy metals above federal standards.
  • The THC levels were all within federal guidelines.
But when it came to dosages advertised on the label…watch out!
  • Four samples were pretty much right on.
  • Two samples cheated you, giving only 60 to 80% of the advertised dosage.
  • Then there were the over-performers: A thousand-milligram sample was really 1,100 milligrams — 10% higher.
  • And one was way over – 210% of what the label said.
“This last sample claimed 500 milligrams in the bottle, and we measured 210% in the bottle,” said Cogell.
“That’s really concerning to me,” said Steve Mueller, who founded Mile High Labs in Loveland, Colorado, and is its CEO. He testified at FDA hearings arguing for federal regulation to ensure accuracy in labeling.
“Right now, there’s no one enforcing any of those things,” Mueller said. “It’s sort of up to the companies to do it themselves.”
“So, that really is the Wild West — whatever you say is what ends up on the label, is what people think they’re buying?” asked Petersen.
“Yeah, you can see that from the results here that it is the Wild West,” Mueller said. “And what you get on the shelf is, you don’t really know.”
To find out if what we don’t know can hurt us, Petersen went to the emergency room at U.C. Health University of Colorado Hospital. There he met Dr. Andrew Monte, a toxicologist and emergency medicine physician who has treated people who’ve ingested too much CBD.
“Patients actually can become more somnolent than would be expected,” Dr. Monte said. “So, they could become very sleepy. Patients can also get nausea, vomiting and diarrhea. Those are the most common side effects from oral CBD.”
And here is another “buyer beware”: don’t turn to CBD and turn away from medications your doctor prescribed.
“It seems to me that people have no problem with paying $50 for a very small vial of cannabidiol, yet they don’t wanna pay their $5 copay for a medicine that’s actually been tested in a randomized controlled clinical trial,” Dr. Monte said.
Now, it’s worth mentioning Dr. Monte tells CBS News that cannabinoids do interact with prescription drugs. But because we lack reliable controlled trials, we don’t have enough detail to understand all the interactions.

FDA issues warning letters to websites selling illegal opioids

The U.S. Food and Drug Administration and the Drug Enforcement Administration (DEA) jointly issued warning letters to four online networks for illegally marketing unapproved and misbranded versions of opioid medicines, the agencies said.
The networks which were issued the warning letters on Monday are Divyata, Euphoria Healthcare Pvt Ltd, JCM Dropship and Meds4U, which operate a total of 10 websites.

The move comes at a time when health regulators in the country are combating the rising use of opioids, which were responsible for 47,600 overdose deaths in the United States in 2017.
Misbranded drugs are those that fail to bear adequate directions for their intended use, the FDA said.
The networks also violated the Controlled Substances Act by not registering the online pharmacies with the DEA despite advertising for the sale of opioids, the agencies said.
In case the online networks fail to take corrective action within 15 working days, the websites’ domain name registrars may be informed, the agencies said.
In June last year, the FDA issued warning letters to nine other online networks operating a total of 53 websites, to stop illegally marketing unapproved versions of opioid medications.

AnaptysBio -13.5% after GALLOP trial data

AnaptysBio (NASDAQ:ANAB) has slipped 13.5% postmarket after posting some positive topline data from its interim analysis of the GALLOP Phase 2 clinical trial.
That analysts was conducted with the first two patients completing a 16-week ANB019 monotherapy study for treating moderate-to-severe generalized pustular psoriasis.
That’s a chronic, life-threatening, rare inflammatory disease that has no approved therapies, the company says.
Enrollment is ongoing and the company expects additional clinical data and a regulatory strategy update in 2020.

Biotech Investors: Mark Your Calendar For These October PDUFA Dates

September turned out to be a fruitful month for FDA approvals. The regulatory agency gave its nod to Ardelyx Inc ARDX 2.89%‘s Ibsrela, a new molecular entity indicated to treat irritable bowel syndrome with constipation in adults.
With Ibsrela, NME approvals for the year totaled 27, lower than the 41 approvals given by the same time last year.
Some of the therapies that crossed the FDA hurdle included Johnson & Johnson JNJ 0.66%‘s Janssen unit’s Erleada for the expanded indication of metastatic castration-sensitive prostate cancer; Novo Nordisk A/S NVO 0.17%‘s oral semaglutide for Type 2 diabetes; and Merck & Co., Inc. MRK 1.54%‘s HIV drugs Pifeltro (doravirine) and Delstrigo (doravirine/lamivudine/tenofovir disoproxil fumarate).
The following are the key PDUFA dates for the upcoming month.

Gilead Seeks Label Expansion For HIV Combo Drug

Company: Gilead Sciences, Inc. GILD 0.76%
Type of Application: sNDA
Candidate: Descovy (emtricitabine 200 mg and tenofovir alafenamide 25 mg tablets)
Indication: Pre-exposure prophylaxis, or PrEP, for HIV-1 infection
Date: Oct. 4 (Estimated, assuming 6-month review period due to the priority voucher submitted with the application)
Descovy was initially approved in April 2016 to be used in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients ages 12 and older.
Gilead is now eyeing approval for Descovy as a preventive treatment for reducing the risk of sexually acquired HIV-1 infection among individuals who are HIV-negative and at risk for HIV.
An FDA panel that met in August voted 16-2 to recommend approval of Descovy as PrEP to reduce the risk of HIV acquisition in men having sex with men and transgender women. The panel voted 8-10 against approving it for cisgender women.

Will Clinuvel’s Phototoxicity Drug See The Light?

Company: Clinuvel Pharmaceuticals Ltd CLVLY 1.26%
Type of Application: NDA
Candidate: Scenesse
Indication: prevention of phototoxicity and anaphylactoid reactions in adult patients with erythropoietic protoporphyria, or EPP
Date: Oct. 6
Scenesse is a controlled release injectable implant containing afamelanotide, which is being developed as a first-line treatment for patients with EPP, a rare genetic metabolic disorder that causes phototoxicity and anaphylactoid reactions when patients expose their skin to light.
In June, the FDA communicated its decision to extend the review period by three months to provide it with more time for the review of the full NDA submission.

Pfenex Seeks Nod For Therapeutic Equivalent of Lilly’s Osteoporosis Drug

Company: Pfenex Inc PFNX 0.94%
Type of Application: NDA
Candidate: PF708
Indication: Osteoporosis
Date: Oct. 7
F708 is a therapeutic equivalent of Eli Lilly And Co LLY 0.53%‘s Forteo, which was approved in 2002 to treat osteoporosis in men and menopausal women who are at high risk of having a fracture.
Forteo’s global sales stood at $1.6 billion in 2018.

Roche’s Blood Vessel Inflammation Drug Awaits FDA Nod

Company: Roche Holdings AG Basel ADR RHHBY 0.03%
Type of Application: sBLA
Candidate: MabThera/Rituxan in combination with glucocorticoids
Indication: treatment of granulomatosis with polyangiitis and microscopic polyangiitis in children two years of age and older
Date: Oct. 11. This is estimated, assuming the filing of the application two months prior to the sBLA acceptance date of June 12.
Granulomatosis with polyangiitis and microscopic polyangiitis are rare, potentially life-threatening diseases affecting small- and medium-sized blood vessels.

J&J’s Seeks Another Label Expansion For Anticoagulant Drug Xarelto

Company: J&J’s Janssen unit
Type of Application: sNDA
Candidate: Xarelto
Indication: prevention of venous thromboembolism in medically ill patients
Date: Oct. 13 (estimated)
Xarelto, an anticoagulant, was initially approved for prophylactic treatment of deep vein thrombosis that may lead to pulmonary embolism in people undergoing knee or hip replacement surgery. Since then, J&J had secured several label expansions for the drug.

FDA To Rule On Second Indication For Flexion’s Osteoarthritis Drug

Company: Flexion Therapeutics Inc FLXN 1.47%
Type of Application: sNDA
Candidate: Zilretta
Indication: repeat administration for osteoarthritis of the knee
Date: Oct. 14
Zilretta was initially approved in Oct. 2017 as an extended-release, intra-articular injection for osteoarthritis knee pain. In the recent second quarter, Zilretta sales rose 60% quarter-over-quarter to $17 million.

Will FDA See Merit In Novartis’ Wet AMD Drug?

Company: Novartis AG NVS 0.55%
Type of Application: BLA
Candidate: Brolucizumab
Indication: wet age-related macular degeneration, or AMD
Date: Oct. 15 (Estimated, based on the submission filing date of April 15)

Second Label Expansion In The Cards For Amgen’s Nplate?

Company: Amgen, Inc. AMGN 0.73%
Type of Application: sBLA
Candidate: Nplate
Indication: treatment of adult patients with immune thrombocytopenia for 12 months or less
Date: Oct. 18 (Estimated, based on the submission filing date of Dec. 19)
Nplate was approved in 2008 as a long-term treatment of adults with chronic immune thrombocytopenia, or low platelet count. Later, Nplate was approved for pediatric patients with the same indication.

Go or No-go For Clearside’s Macular Edema Drug?

Company: Clearside Biomedical Inc CLSD 4.28%
Type of Application: NDA
Candidate: Xipere
Indication: treatment of macular edema associated with uveitis
Date: Oct. 19
Xipere, chemically triamcinolone acetonide ophthalmic suspension, is formulated as suprachoroidal Injection for the treatment of macular edema associated with uveitis.

Assertio Seeks Assent For Adrenocortical Insufficiency Diagnostic Drug

Company: Assertio Therapeutics Inc ASRT 2.29%
Type of Application: NDA
Candidate: Cosyntropin
Indication: Diagnostic drug for detecting adrenocortical insufficiency
Date: Oct. 19
Long-acting cosyntropin is an alcohol-free formulation of a synthetic analogue of adrenocorticotropic hormone. It’s secreted by the pituitary gland and is responsible for the stimulation of the adrenal cortex. Contingent on FDA approval, the company expects to launch the product in the U.S. by early 2020.

Can Alexion’s Ultra-Rare Disease Drug Snag Second Approval?

Company: Alexion Pharmaceuticals, Inc. ALXN 0.17%
Type of Application: sBLA
Candidate: Ultomiris
Indication: Atypical hemolytic uremic syndrome, or aHUS
Date: Oct. 19
aHUS, also known as complement-mediated thrombotic microangiopathy, is a severe and chronic ultra-rare disease that can cause progressive damage to vital organs, predominantly the kidneys, leading to kidney failure and premature death.
Ultomiris was previously approved in December 2018 for the treatment of adult patients with paroxysmal nocturnal hemoglobinuria.

Can Foamix Acne Treatment Clear FDA Hurdle?

Company: Foamix Pharmaceuticals Ltd FOMX 0.98%
Type of Application: NDA
Candidate: FMX101
Indication: treatment of inflammatory lesions of non-nodular moderate-to-severe acne vulgaris in patients 9 years and older
Date: Oct. 20

Eton Braces For Decision On Ready-to-use Phenylephrine

Company: Eton Pharmaceuticals Inc ETON 1.94%
Type of Application: NDA
Candidate: ET-202
Indication: ready-to-use injectable formulation of phenylephrine
Date: Oct. 21

Melinta On Track For Another Approval For Antibacterial Drug?

Company: Melinta Therapeutics Inc NASDAQ: MLNT) and Ligand Pharmaceuticals Inc. LGND 0.6%
Type of Application: sNDA
Candidate: Baxdella
Indication: community-acquired bacterial pneumonia, or CABP
Date: Oct. 24
BAXDELA, in both capsule and IV formulations, was approved by the FDA in 2017 for the treatment of adult patients with acute bacterial skin and skin structure infections caused by designated susceptible bacteria.

GlaxoSmithKline’s Ovarian Cancer Drug to Add Another Indication?

Company: GlaxoSmithKline plc GSK 0.8%
Type of Application: sNDA
Candidate: Zejula
Indication: Ovarian cancer
Date: Oct. 24
Zejula, or niraparib, came into Glaxo’s stable following its acquisition of Tesaro.
Glaxo is now seeking approval of Zejula for the treatment of advanced ovarian, fallopian tube or primary peritoneal cancer patients who have been treated with three or more prior chemotherapy regimens and whose cancer is associated with either BRCA mutation or homologous recombination deficiency.
Previously, Zejula was approved as a maintenance treatment of women with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy.

Adamis’ Opioid Overdose Drug Awaits Clearance

Company: Adamis Pharmaceuticals Corp ADMP 5.94%
Type of Application: NDA
Candidate: Higher dose naloxone spray
Indication: opioid overdose
Date: Oct. 31
Adamis recently said it was conducting additional pharmacokinetic studies comparing its long-acting naloxone spray, provisionally given the name Zimhi, to a relevant comparator. The company said it will forward data from the study to the FDA later this month.

Adcom Schedule

FDA’s Antimicrobial Drugs Advisory Committee will meet Wednesday, Oct. 16 to discuss SHIONOGI & CO L/ADR SGIOY 1.95%‘s NDA for cefiderocol lyophilized powder for intravenous administration for the treatment of complicated urinary tract infection, including pyelonephritis due to gram-negative bacteria in patients with limited or no alternative treatment options.
The Bone, Reproductive and Urologic Drug Advisory Committee is scheduled to meet on Tuesday, Oct. 29 to discuss AMAG Pharmaceuticals, Inc. AMAG 4.55%‘s sNDA for Makena, which is being evaluated for reducing the risk of recurrent preterm birth or improving neonatal mortality and morbidity.
The same committee will discuss Wednesday, Oct. 30 Agile Therapeutics Inc AGRX 5.8%‘s NDA for Twirla — a low-dose combo hormonal contraceptive patch — to be used for birth control.

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.

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.

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

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.

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 ,

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.
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.

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.

Bristol-Myers higher after Opdivo update

Bristol-Myers Squibb (BMY +1.8%) is out with results from a Phase 3 Attraction trial of Opdivo for patients with esophageal cancer.
The company says Opdivo demonstrated a 23% reduction in the risk of death and 2.5-month improvement in median overall survival compared to chemotherapy
BMY management is updating on the results at a Presidential Symposium during the European Society for Medical Oncology 2019 Annual Congress.
Source: Press Release

Pfizer eyes commercial scale-up as Array colorectal cancer combo hits its marks

Positive new colorectal cancer data has Pfizer envisioning a launch for its newly acquired Array BioPharma meds. And the company is getting prepared.
Monday at the European Society for Medical Oncology annual meeting, the New York drugmaker presented data showing that its Braftovi and Mektovi, when combined with anti-EGFR drug Erbitux, could extend previously treated patients’ lives for a median nine months, compared with just 5.4 months for standard-of-care therapy. In other words, it decreased the risk of death by 48%.
The numbers have Pfizer “very excited” and planning an FDA submission for the fourth quarter of this year, Andy Schmeltz, global president and general manager of Pfizer’s oncology unit, said.
The prognosis for this patient pool is “very poor, and to have a new option that can really extend life … is very significant,” he said.

But the company is also “mindful of the resources that will be required for a successful launch” in that arena—resources that hadn’t yet been allocated when Pfizer swallowed Braftovi and Mektovi’s maker, Array, for $11.4 billion in July.
“There had not been the scaling up to prepare to launch in colorectal cancer, and that’s what we’re partnering right now to prepare for,” Schmeltz said, adding that “we’re going to size and scale as appropriate.”
Thanks to the acquisition, the pharma giant now also has the chance to throw its weight behind the duo in melanoma, where Array got off to a flying start. After just a year on the market, the combo is already grabbing 1 in 3 new patient starts, despite competition from two other in-class combos.
Still, “the focus for Array had really been in the cancer centers,” Schmeltz said. Given that the company had only been marketing the drugs for a year when it agreed to tie the knot with Pfizer, its reps “hadn’t really had the opportunity yet to engage more broadly with community-based oncologists.”
“This gives us the opportunity to do that,” he noted.

While Pfizer will add staffers and funding to the effort, though, it’ll still be leaning on Array for its experience in the melanoma field. “Pfizer Oncology did not have a presence in melanoma, so we need the expertise that the Array colleagues bring to the table,” Schmeltz said. He pointed out that “it’s not an integration about synergy,” which is a pharma favorite term for cost-cutting.
“We’re working together to bring” the Array employees on board, and everything’s going very smoothly, he said.

What Do the J&J and Purdue Pharma Outcomes Mean to the Pharma Industry?

Opioid abuse and addiction continue to ravage communities across the United States. Nora Freeman Engstrom of Stanford Law School reported in Suing the Opioid Companies, on August 30, 2018, that 2.4 million Americans had an opioid-use disorder with 300,000 lives lost, including 42,000 in 2016 alone. The financial burden on state governments in the form of increases in the cost for public health services, law enforcement, medical treatment, rehabilitation programs, housing, and related services has left state governments seeking the funds required to adequately deal with this crisis. Oklahoma was the first state to file suit against opioid manufacturers. The success of their legal strategy will have a significant impact on the opioid–and pharmaceutical–industry going forward.
What Oklahoma claimed
In the Judgement After Non-Jury Trial for the State of Oklahoma vs. Multiple Pharmaceutical Defendants in the District Court of Cleveland County during the spring/summer of 2019, the document shows that the state of Oklahoma claimed the defendants caused a public nuisance, for which the state was seeking relief in the form of “abatement of the nuisance.” None of the parties disputed the fact that Oklahoma was suffering a crisis related to the use of opioid drugs. They also agreed on several other indicators of the extent of this crisis, including the fact that in 2015, enough opioid pills were dispensed in Oklahoma “for every adult to have 110 pills.”
In his ruling, Judge Thad Balkman wrote that the challenged conduct was the “Defendants’ “misleading marketing and promotion of opioids. … Defendants engaged in a false, misleading, and deceptive marketing campaign designed to convince Oklahoma doctors, patients, and the public at large that opioids were safe and effective for the long-term treatment of chronic, non-malignant pain. The greater weight of the evidence shows that Defendants did, in fact, engage in such false and misleading marketing and the law is clear that such conduct qualifies as the kind of act or omission capable of sustaining liability under Oklahoma’s nuisance law.”
The action by the state of Oklahoma was successful where the suits of individuals and class action had not been because the individual and class action suits dealt with the specifics of an individual or group. Since the medications in question were FDA-approved and the individuals had chosen to take the medication, it was difficult to prevail. With class action suits, it was extremely difficult to assemble a group that had enough of the essential traits in common for the suit to succeed. By using the fact that the opioid addiction situation in Oklahoma was a crisis that had created a public nuisance, delving into the private lives of specific individuals was not required.
Ultimately, the court agreed that the defendants had caused a nuisance as defined to consist “in unlawfully doing an act, omitting to perform a duty, which act or omission annoys, injures or endangers the comfort, repose, health or safety of others; or, in any way renders other persons insecure in life, or in the use of property…” Judge Balkman ordered Johnson & Johnson to pay $572 million – an amount significantly less than sought, but one The New York Times reported would pay for a year’s worth of the services needed to combat the epidemic in Oklahoma. Purdue Pharma settled for $270 million in this same suit, one of the many in which it was named as a defendant.
Purdue Pharma, together with members of the Sackler family that own the company, is the name in a large opioid settlement relating to a lawsuit. Filed in December 2018 by Connecticut and a number of other states, it alleges that the company continued to push patients toward OxyContin® even after the addiction rate became evident. Connecticut Attorney General William Tong told ABC News in April 2019, “Our investigation left no room for doubt—Purdue and the Sacklers ignored all human cost while pushing deadly opioids in blind pursuit of profit.”
In a September 9th interview on NPR with North Carolina Attorney General Josh Stein, host Brian Mann – who covers opioid litigation for NPR – explained that “there’s a legal argument being made by some of these states [still seeking abatement] that the Sacklers effectively stripped billions of dollars out of Purdue Pharma over the years. In part, it’s alleged, because the family suspected their company would eventually face lawsuits like this. So, 17 states are already suing the Sacklers Directly to try to claw back some of these profits.” Stein agreed, stating “many states, like mine, will be filing lawsuits against the Sacklers in their individual capacity in creating this epidemic. I think almost more than any other family and company, they have to wear that burden.” On September 15, Purdue Pharma filed for bankruptcy in Chapter 11 as part of their $3 billion settlement of the 2018 suit. Whether or not future litigation directly against family members will succeed remains to be seen.
What it Means for Pharma
In the opinion of Stanford legal experts Michelle Mello and Nora Freeman Engstrom in an August paper, the outcome of the case was not a foregone conclusion. Nuisance claims are very hard to prove and by the time the suit went to court, “Oklahoma’s various causes of action got winnowed down to the singular claim that J&H had created a public nuisance by aggressively and deceptively marketing opioid products to Oklahoma’s doctors and patients.” As the first case of its kind, the Oklahoma case is a bellwether case – it leads the way to future litigation.
“The verdict,” say the authors, “suggests that this litigation has legs, and that judges and juries may be willing to pin blame not just on Purdue, the maker of OxyContin®, but on others who played an arguably less central role in fueling this public health crisis.” This has to be a concern to pharma companies and others in the industry alike. The fact that FDA-approved opioid drugs, marketed and sold through widely accepted means, have been the target of successful litigation as a public nuisance is certainly a game changer. The potential culpability of companies in the pharma space has undergone a paradigm shift.
Mello and Engstrom summed it up well. “What is striking is how damming Judge Balkman’s factual conclusions about J&J’s conduct are, and how similar they are to the allegations made against other opioid manufacturers in other cases. All the things he objected to regarding J&J’s marketing practices are things that others, too, allegedly have done. Some of them are things that multiple companies banded together to do. Plaintiff’s attorneys should be feeling pretty confident about their chances of persuading other courts that those practices are problematic.”

Dana-Farber Study Confirms Accuracy of GRAIL’s Blood Test for Cancer

A new blood test in development from GRAIL, Inc. and studied by investigators at the Dana-Farber Cancer Institute has the ability to accurately screen for numerous types of cancer.
Data from the study was presented at the European Society for Medical Oncology (ESMO) 2019 Congress. The study showed that the next-generation sequencing technology can probe DNA for chemical tags known as methylation that influence whether genes are active or inactive, Dana-Farber said this morning. According to the study, the technology probed 3,600 blood samples, some from patients with cancer and some from those who had not been diagnosed, and the test was able to pick up on cancer signals. Additionally. The test correctly identified the tissue from where the cancer began. Dana-Farber said the test’s specificity was high, as was its ability to pinpoint the organ or tissue of origin, researchers found.
GRAIL’s test looks for DNA, which cancer cells shed into the bloodstream when they die. In contrast to “liquid biopsies,” which detect genetic mutations or other cancer-related alterations in DNA, the technology focuses on modifications to DNA known as methyl groups, Dana-Farber said. Methyl groups are chemical units that can be attached to DNA, in a process called methylation, to control which genes are “on” and which are “off.” Abnormal patterns of methylation turn out to be, in many cases, more indicative of cancer — and cancer type — than mutations are. The test zeroes in on portions of the genome where abnormal methylation patterns are found in cancer cells, Dana-Farber noted in its announcement.
Dana-Farber’s study showed that the GRAIL test had a specificity of 99.4%, meaning only 0.6% of the results incorrectly indicated that cancer was present. The sensitivity of the assay for detecting a pre-specified high mortality cancers was 76%. Within this group, the sensitivity was 32% for patients with stage I cancer; 76% for those with stage II; 85% for stage III; and 93% for stage IV. Sensitivity across all cancer types was 55%, with similar increases in detection by stage. For the 97% of samples that returned a tissue of origin result, the test correctly identified the organ or tissue of origin in 89% of cases, Dana-Farber said in its announcement.
Dana-Farber’s Geoffrey Oxnard and lead author of the study said previous work indicated that methylation-based assays outperform traditional DNA-sequencing approaches to detecting multiple forms of cancer in blood samples.
“The results of the new study demonstrate that such assays are a feasible way of screening people for cancer,” Oxnard said in a statement. He added that the results of this study indicate that if the test were in wide use, it could help patients receive more effective treatments.
Data presented by GRAIL in the spring at the 2019 American Society of Clinical Oncology showed GRAIL’s investigational multi-cancer blood test detected a strong signal for 12 deadly cancer types at early stages with a very high specificity of at least 99%. The test was aimed at 12 pre-specified cancer types, including anorectal, colorectal, esophageal, gastric, head and neck, hormone receptor-negative breast, liver, lung, ovarian, and pancreatic cancers, as well as multiple myeloma and lymphoid neoplasms. These types of cancer make up about 63% of cancer deaths in the United States, the company said. The combined analysis of this group of cancers showed robust detection at early stages, 34%, 77%, and 84% at stages I, II, and III, respectively, GRAIL noted at the time it presented its own data.

Zymeworks upped to Strong Buy by Raymond Jame

Target to $40 from $36

Unitedhealth cut to Market Perform by BMO

Humana cut to Market Perform by BMO

Target to $290 from $345

Cigna upped to Outperform by BMO

Bellus started at Buy by Jefferies

Adamas cut to Underperform by B of A

Lexicon Pharma -13.8% as Mako warns of deal breakup ‘disaster’

Lexicon Pharmaceuticals (NASDAQ:LXRX) is now off 13.8% today on heavy volume following a very bearish take from Seeking Alpha contributor Mako Research.
A breakup of the company’s deal with Sanofi for develping sotaglifozin will throw responsibility for late-stage trials to Lexicon, accelerating cash burn, Mako says — and the company admits it doesn’t have enough cash to finish the ongoing trials, “much less fund a commercial launch.”
“On closer examination it’s clear that the terms of the termination are a disaster for Lexicon and its investors,” Mako says.
Sell-side analysts rate the stock Outperform on average, while Seeking Alpha authors are Neutral overall. The stock has a Quant Rating of Very Bearish.

AstraZeneca, Merck’s Lynparza meets primary goal in late-stage study

AstraZeneca (AZN -1.1%) and Merck (MRK +1.5%) report PROfound Phase 3 clinical trial results showed statistically significant and clinically meaningful improvement with Lynparza (olaparib) in the primary endpoint of radiographic progression-free survival (rPFS) in certain tumors reducing the risk of disease progression or death by a median of 7.4 months vs. 3.6 months for those receiving abiraterone or enzalutamide; LYNPARZA reduced the risk of disease progression or death by 66% for these men.
Trial also met key secondary endpoint of rPFS in overall HRRm population. where Lynparza reduced the risk of disease progression or death by 51% and improved rPFS to a median of 5.8 months vs. 3.5 months for those receiving abirateron or enzalutamide.
Secondary endpoint of median time to pain progression was not reached.
Trial showed a confirmed overall response rate, a key secondary endpoint of 33.3% for Lynparza vs. 2.3% for abiratone or enzalutammide in patients with BRCA1/2 or ATM mutations.
Safety and tolerability profile of Lynparza in the PROfound trial was in line with that observed in prior clinical trials.

Pfizer reports positive data from late-stage BEACON CRC trial

Pfizer (NYSE:PFEannounces results from the interim analysis of the Phase 3 BEACON CRC trial evaluating the combination of BRAFTOVI (encorafenib), MEKTOVI (binimetinib), and cetuximab (BRAFTOVI Triplet), in patients with advanced BRAFV600E-mutant metastatic colorectal cancer (mCRC), following one or two lines of therapy.
The results show significant improvements in overall survival and objective response rates for the BRAFTOVI Triplet and BRAFTOVI Doublet combination (BRAFTOVI and cetuximab), compared to cetuximab plus irinotecan-containing regimens (Control), and provide analysis of the efficacy and safety of the BRAFTOVI Triplet compared to the BRAFTOVI Doublet.
BRAFTOVI Triplet showed a median OS of 9.0 months, compared to 5.4 months for Control. An improved ORR of 26% was observed in BRAFTOVI Triplet compared to 2% for Control.
These data will be presented today at the 2019 European Society for Medical Oncology Congress in Barcelona, Spain.
The Company expects to submit the results of the trial for marketing approval in U.S. in Q4 2019.

Amgen off after early stage AMG 510 data disappoints

Amgen (NASDAQ:AMGN) moves down 2.0% in premarket trading after disclosing new data from the ongoing early-stage study evaluating AMG 510 in patients with previously treated KRAS G12C-mutant solid tumors.
The Phase 1 study enrolled 76 patients with KRAS G12C-mutant solid tumors; data presented at the European Society for Medical Oncology 2019 Congress include a subset of 55 evaluable patients as of the July 2019 cutoff.
Of 29 with colorectal cancer, 12 patients received target dose of 960 mg once daily and 10 remain on treatment; one patient in dose cohort experienced partial response and 10 had stable disease for a disease control rate of 92%.
For 13 evaluable patients with non-small cell lung cancer, receiving 960 mg, seven (54%) achieved a partial response at one or  more timepoints, and six achieved stable disease.
AMG 510 continues to be well-tolerated with no dose-limiting toxicities.
Amgen is initiating combination studies to further explore potential of AMG 510 in lung and colorectal tumors.
Mirati Therapeutics (NASDAQ:MRTX), which has a similar molecule called MRTX849, is falling 2.2% in premarket action.