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Tuesday, July 31, 2018

Neuralstem starts Phase 2 for ischemic stroke stem cell therapy

Neuralstem announces initiation of Phase 2 trial of NSI-189  Neuralstem announced the initiation of a Phase 2 clinical trial evaluating NSI-566, the Company’s lead neural stem cell candidate, as a potential treatment for ischemic stroke. Neuralstem announced the positive topline results of Phase 1 stroke study in the 2018 ISSCR (International Society for Stem Cell Research) abstract on June 23, 2018. The trial will be taking place at Bayi Brain Hospital in Beijing, China, commencing on August 1, 2018. Managing the trial will be James Li, Ph.D., Executive Vice President of Asia Operations of Suzhou Neuralstem Ltd, a wholly owned subsidiary of Neuralstem, Inc., located in Suzhou, China. Dr. Li has been made the Manager and a Registered Agent of Suzhou Neuralstem. Neuralstem will be allocating US$3 million toward this trial.

Evercore ISI Downgrades resTORbio Inc. (TORC) to In Line

Evercore ISI downgraded resTORbio Inc. (NASDAQ: TORC) from Outperform to In Line with a price target of $17.00 (from $29.00).

Sanofi stockpiles drugs to prepare for hard Brexit

Sanofi has been preparing drug shortage contingency plans for over a year in the event that the U.K. fails to reach an agreement with the EU on Brexit, the Wall Street Journal reports, citing a person familiar with the matter. The move is the most recent sign that big European companies are concerned about the prospects of a hard Brexit, where the U.K. doesn’t reach a deal over its future relationship with the EU, the report notes

Google of CRISPR? Tech legends Tim Cook, Jeff Huber back Mammoth Bio

A startup led by a group of Bay Area grad students says it’s building a platform that harnesses the “search engine” function of CRISPR, winning $23 million in backing from a slew of high profile investors Tuesday.
The company, called Mammoth Biosciences, was co-founded by CRISPR legend Jennifer Doudna — one of the most famous scientific pioneers behind CRISPR/Cas9 gene editing tech. The other founders include the 29-year-old CEO Trevor Martin, a Stanford PhD, and CTO Ashley Tehranchi, also out of Stanford. The duo launched the company with the help of two students in Doudna’s lab: Janice Chen and Lucas Harrington, who will lead scientific research. Doudna heads up the scientific advisory board.

Operating under stealth mode until recently, Mammoth first stepped out this April with news that it planned to create a platform for diagnostics. With tech in-licensed from Berkeley, the company wants to apply CRISPR tech to new frontiers.
While many describe CRISPR as the “scissors” of gene editing, cutting DNA and replacing bits of genetic material where needed, Mammoth is more interested in the search function of CRISPR.

“CRISPR is biology’s search engine first,” Martin told TechCrunch in an interview. “Control + F is the exciting part. At core it’s just this amazing search engine that we can use to find things. The way that we search for things is just like Google.”
Now, Mammoth has a round of fresh capital to invest in its platform and staff. The $23 million round was led by Mayfield with participation from NFX and 8VC. Apple’s Tim Cook and the first CEO of Silicon Valley cancer screening startup Grail, Jeff Huber, also joined the round for an unspecified amount.

Blair Ups Medpace, Sees ‘Strong Biotechnology Funding Environment’

Medpace Holdings Inc MEDP 30.38% reported better-than-expected second-quarter earnings Monday afternoon.

The Analyst

William Blair’s John Kreger upgraded Medpace from Market Perform to Outperform.

The Thesis

The company reported adjusted EPS of 67 cents on an ASC 605 basis in Q2, well above Kreger’s 39-cent estimate. (See the analyst’s track record here.)
The beat came due due to better gross margins and higher revenue, the analyst said, naming the earnings beat, excellent bookings and guidance raise as the drivers behind William Blair’s upgrade.
Medpace increased 2018 guidance and said it expects higher revenue by $39 million and earnings that are 65 cents per share higher on an ASC 605 basis, Kreger said. His estimate is similar, as as he expects $40 million higher revenue and a 60-65-cent EPS increase on an ASC 605 basis.
“We view the strong biotechnology funding environment as an ongoing positive for all of the CROs, but particularly for Medpace given its larger exposure to smaller clients,” the analyst said.
William Blair expects Medpace to perform well in the second half of the year and in 2019.

Heat therapy boosts mitochondrial function in muscles

A new study finds that long-term heat therapy may increase mitochondrial function in the muscles. The discovery could lead to new treatments for people with chronic illness or disease. The study — the first of its kind in humans — is published ahead of print in the Journal of Applied Physiology.
Mitochondria, the “energy centers” of the cells, are essential for maintaining good health. A decrease in the number or function of mitochondria may contribute to chronic and potentially serious conditions such as heart disease, chronic obstructive pulmonary disease and type 2 diabetes. Exercise has been shown to create new mitochondria and improve function of existing mitochondria. However, some people with chronic illnesses are not able to exercise long enough — previous research suggests close to two hours daily — to reap the benefits. Rodent studies have suggested that heat exposure may also induce the production of more mitochondria.
Researchers from Brigham Young University in Utah studied 20 adult volunteers who had not participated in regular exercise in the three months prior to the study. The research team applied two hours of shortwave diathermy — a type of heat therapy generated by electrical pulses — to the thigh muscles of one leg of each person every day. The researchers based the six-day trial of heat on the minimum amount of exercise needed to measure changes in muscle, or about two hours each day. They designed the treatment to mimic the effects of muscle heating that occurs during exercise. The therapy sessions increased the temperature of the heated leg by approximately 7 degrees F. Each participant’s other leg served as a control, receiving no heat therapy or temperature change. The researchers looked at mitochondria content in the muscles on the first day of therapy and 24 hours after the last treatment.
Mitochondrial function increased by an average of 28 percent in the heated legs after the heat treatment. The concentration of several mitochondrial proteins also increased in the heated legs, which suggests that “in addition to improving function, [repeated exposure to heat] increased mitochondrial content in human skeletal muscle,” the research team wrote.
“Our data provide evidence to support further research into the mechanisms of heat-induced mitochondrial adaptations,” the researchers explained. People who are not able to exercise for long periods of time due to their health may benefit from [heat] treatments.
Story Source:
Materials provided by American Physiological SocietyNote: Content may be edited for style and length.

Journal Reference:
  1. Paul Samuel Hafen, Coray N Preece, Jacob R. Sorensen, Chad R. Hancock, Robert D. Hyldahl. Repeated exposure to heat stress induces mitochondrial adaptation in human skeletal muscleJournal of Applied Physiology, 2018; DOI: 10.1152/japplphysiol.00383.2018

Long-Term Heart Risks After Breast Cancer Therapy

Breast cancer survivors treated with older irradiation protocols remained at significant risk of treatment-related cardiovascular disease (CVD) for decades afterward, authors of a large retrospective review concluded.
Encompassing a treatment period of almost 40 years beginning in 1970, the review showed that anthracycline-containing chemotherapy plus irradiation of the internal mammary chain (IMC) was associated with a heart failure (CHF) risk nine times greater than that of women in the general population. Anthracycline therapy alone increased heart failure risk four times over that of the general population, according to Flora E. van Leeuwen, PhD, of the Netherlands Cancer Institute in Amsterdam, and colleagues.
IMC irradiation also increased the risk of ischemic heart disease (IHD) and valvular heart disease (VHD), regardless of whether the radiation treatment was on the right or left side. In many instances, the CVD risk did not emerge for 20 years or more after treatment for breast cancer, they reported in the British Journal of Cancer.
“Our results are relevant to a large number of breast cancer survivors treated with older IMC regimens, who may remain at an elevated CVD risk for an extensive period,” the authors stated. “Follow-up in our study was too short to detect or reject an IHD risk increase associated with IMC irradiation during 2000 to 2009.”
“Recent studies showing improved breast cancer survival after IMC irradiation, still have insufficient follow-up to detect an increased CVD risk, which, as we report, continues into the third decade after treatment,” they noted.
An unrelated study showed a dose-dependent association between irradiation for breast cancer and the risk of injury to the left ventricle (LV) and coronary artery segments. Covering a 43-year period beginning in 1958, the data suggested that all coronary segments “are sensitive to radiation and that doses to all segments should be minimized,” Carolyn Taylor, PhD, of the University of Oxford in England, and colleagues, wrote in the Journal of Clinical Oncology.
Better Survival, New Risks
Advances in early diagnosis and treatment of breast cancer substantially improved survival over the past several decades. Radiation therapy and anthracycline-based chemotherapy have contributed to improved survival but at a recognized expense of an increased CVD risk, Van Leeuwen’s group noted.
Anthracycline-based chemotherapy has a dose-dependent association with cardiomyopathy and heart failure, although the cumulative incidence varied in prior studies. Documented heart effects of radiation therapy include IHD and VHD, and some studies have suggested the effects are dose-dependent.
Initial studies suggested the adverse heart effects of radiation therapy emerged about 10 years after exposure, but more recent analyses have shown that the risk begins to increase within 5 years of exposure, the authors continued.
Given the growing population of breast cancer survivors, investigators sought to quantify the long-term CVD risks following treatment for the disease. The analysis comprised 14,645 Dutch patients age <62, treated for early breast breast cancer during 1970 to 2009, with follow-up to 2012.
Following surgery, 56% of patients received radiation therapy alone, 3% received chemotherapy alone, 30% received both, and 11% received neither. For patients who received radiation to the breast or chest wall but not the IMC, the usual radiation dose to the heart ranged between 4 and 6 Gy until 2000 to 2009, when it decreased to about 1.5 Gy.
When the radiation field included the IMC, the typical dose to the heart ranged from 12 to 22 Gy, except for the subgroup of women who received radiation to the IMC and breast, which was associated with a heart dose of 9 Gy during 2000 to 2009.
When the IMC was not exposed, the CVD rate ratio (RR) for left-versus-right sided beast irradiation was 1.11, which failed to achieve statistical significance (95% CI 0.93-1.32). IMC irradiation at a dose range of 9-16 Gy versus right-sided breast irradiation only significantly increased the risk of total CVD, IHD, VHD, and CHF (RR 1.6-2.4). IHD risk remained elevated for at least 20 years after treatment.
Anthracycline-based chemotherapy significantly increased the risk of CHF versus the general Dutch population of women within 5 years of treatment and remained elevated at least 10 to 15 years after treatment (HR 4.18, 95% CI 3.07-5.69). The combination of IMC irradiation plus anthracycline-based chemotherapy increased CHF risk more than nine-fold versus women exposed to neither treatment (HR 9.23, 95% CI 6.01-14.18).
The study had some limitations including the potential for unreported CVD events.
Higher RT Doses, Higher Risk
Taylor’s group analyzed the association between radiation therapy and CVD risk in 456 women who received radiotherapy for breast cancer from 1958 to 2001 and who subsequently had major coronary events. Radiation dose to five LV segments could be estimated for 414 patients. Additionally, radiation dose to six coronary segments was estimated for a subgroup of 133 patients who had documented coronary artery disease associated with ≥70 stenosis.
Of the 414 patients with LV injury, 243 had left-sided breast cancer and 171 had right-sided cancer (RR 1.42, 95% CI 1.17-1.73), reflecting a higher typical LV radiation dose in left-sided cancer, the authors noted.
For the five segments assessed, the ratios for left-versus-right sided radiotherapy were 0.94 for inferior (95% CI 0.70-1.25); 1.42 for lateral (95% CI 1.04-1.95); 2.09 for septal (95% CI 1.37-3.19); 1.85 for anterior (95% CI 1.39-2.46); and 4.64 for apex (95% CI 2.42-8.90). Corresponding radiation dose differences for the five segments were 2.7, 4.9, 7.2, 10.4, and 21.6 Gy (P<0.001 for trend).
For the subgroup of women with coronary artery disease, the ratios for left-versus-right radiotherapy for the six segments evaluated were 0.48 for proximal right coronary artery (95% CI 0.26-0.91); 1.69 for mid/distal right coronary (95% CI 0.85-3.36); 1.46 for proximal circumflex (95% CI 0.72-2.96); 1.11 for distal circumflex (95% CI 0.45-2.73); 1.89 for proximal left anterior descending (95% CI 1.07-3.34); and 2.33 for mid/distal left anterior descending (95% CI 1.19-4.59). The corresponding left-minus-right radiation dose differences were -5.0, -2.5, 1.6, 3.5, 9.5, and 38.8 Gy (P=0.002 for trend).
“For individual LV and coronary artery segments, higher radiation doses were strongly associated with more frequent injury, suggesting that all segments are sensitive to radiation and that doses to all segments should be minimized,” the authors concluded.
They noted a study limitation was that “individual CT information was unavailable because the women were irradiated before the era of three-dimensional CT radiotherapy planning. Therefore, it was necessary to estimate cardiac doses retrospectively using a typical CT scan.”
The study by Van Leeuwen’s group was supported by the Dutch Cancer Society, Cancer Research UK, the British Heart Foundation Centre for Research Excellence, Oxford, the UK Medical Research Council, and the British Heart Foundation to the Oxford University Clinical trial Service Unit.
Van Leeuwen and co-authors disclosed no relevant relationships with industry.
The study by Taylor’s group was supported by Cancer Research UK, the University of Oxford under the Department of Health Policy Research Programme, the UK Medical Research Council, the British Heart Foundation to the Oxford University Clinical Trial Service Unit, and by the British Heart Foundation Centre for Research Excellence at the University of Oxford.
Taylor disclosed no relevant relationships with industry. One or more co-authors disclosed relevant relationships with AstraZeneca, Atossa Genetics, and Celgene.

Gilead investors see Celgene veteran Jackie Fouse as top pick for CEO spot

Biotech investors may still be getting over the shock of the departure of Gilead’s top two executives, but that hasn’t stopped analysts from speculating about who will be the troubled company’s next CEO.
Topping the list of a possible replacement for departing CEO John Milligan, Ph.D., is Jacqualyn “Jackie” Fouse, Ph.D., who had a seven-year stint as the chief financial officer and then chief operating officer at Celgene. That’s the suggestion from RBC Capital Markets analyst Brian Abrahams, who conducted an investor survey and revealed the results to investors in a note he sent out Monday.
Yes, Celgene had some troubles of its own during Fouse’s tenure, and she would have to relocate from the East Coast, but “given her track record (both vision and execution), relationship with the Street, and ability to attract talent, we believe her presence at [Gilead] would be well received,” Abrahams wrote.
The news of Milligan’s departure, which was announced along with the retirement of chairman and former CEO John C. Martin, Ph.D., came during the company’s second-quarter earnings report last week. The financial results revealed a continuing downward slide for the company, which has been suffering from the rapid drop in demand for its hepatitis C stars Sovaldi and Harvoni. During the quarter, product sales fell 21% year over year to $5.6 billion, and earnings per share plummeted 40% to $1.39.

So does Fouse have the chops to engineer the turnaround Gilead so desperately needs? The company is counting on some of its newer products to drive revenue growth going forward, including CAR-T cancer therapy Yescarta, so her oncology background would certainly come in handy. Fouse joined Celgene as CFO in 2010, moving on to take over the company’s hematology and oncology unit, before being named president and COO in 2016.
Fouse left Celgene abruptly last February, after the company named Mark Alles as its new CEO. Fouse and Alles had apparently been competing to take over the C-suite from Bob Hugin, who retired to run for a U.S. Senate seat. Still, Fouse’s departure was a surprise, and some industry watchers speculated at the time that she would soon show up as CEO of another biotech company. Fouse reportedly turned down the opportunity to take over as CEO of Teva last August and she’s now executive chairman of Dermavant, a company that’s developing a drug to treat excessive sweating and that recently bought the rights to a late-stage experimental drug to treat psoriasis and atopic dermatitis from GlaxoSmithKline.

Fouse was the winner of Abraham’s investor survey by a wide margin, though some other interesting names were proposed as good choices to lead Gilead. Some respondents suggested the company should find its next CEO via a merger, perhaps with Vertex (Jeff Leiden) or Pfizer (Ian Read). Others proposed that Gilead steal away the head of another big biotech company, such as Amgen CEO Bob Bradway or Roche Pharma CEO Daniel O’Day. Chief scientific officers might also be well-suited to take on Gilead’s challenges, some said, including Merck’s Roger Perlmutter and GlaxoSmithKline’s Hal Barron.
Gilead is expected to select a replacement for Milligan by the end of the year, when he is scheduled to step down. Martin plans to depart when the new CEO is named.
The prospect of such a radical change in the top ranks of Gilead has generated some agita on the Street. Leerink analyst Geoffrey Porges fears that “given the company’s mixed hiring record, the appointee may not necessarily be an individual with immediate industry or investor credibility,” he wrote in a note to investors last week. Jefferies analyst Michael Yee acknowledged in a note that the change “brings uncertainty” in the short term.
Still, wrote Yee, the prospect of a “new” future for Gilead also offers hope for “more pipeline, more bold steps, more aggressive BD, and a chance for PE expansion and stock appreciation.” Gilead’s decision to clean house may be nerve-racking, he wrote, but it could very well transform the company “from pharma-like, to more biotech-like.”

Molina 2Q Results; Increases Fiscal Year 2018 Guidance

  • Net income of $3.02 per diluted share on a GAAP basis in the second quarter of 2018, compared with $1.64 per diluted share in the first quarter of 2018
  • Second quarter 2018 results include a net benefit of $0.83 per diluted share for non-run rate items, primarily relating to the 2017 Marketplace risk adjustment
  • Premium revenue increases $191 million, or 4.4%, in the second quarter of 2018 compared with the first quarter of 2018
  • Medical care ratio of 85.3% in the quarter
  • General and administrative expense ratio of 6.9% in the quarter
  • Net profit margin of 4.1% in the quarter and 3.2% year to date
  • 2018 guidance increases by $3.00 per diluted share at the midpoint to a range of $7.15 – $7.35 net income per diluted share on a GAAP basis
  • 2018 guidance includes the net benefit of $0.96 per diluted share for the non-run rate items recorded in the first half of the year

FDA’s Gottlieb on antimicrobial stewardship in veterinary settings

Antimicrobial resistance is a global public health challenge. Antimicrobial drugs have been widely used in human and veterinary medicine for more than 60 years. When used judiciously, antimicrobials can effectively fight bacterial infections. However, we know that overuse or misuse of these drugs promotes the development of antimicrobial-resistant bacteria.
For all of these reasons, it’s critical that we implement good antimicrobial stewardship practices in human healthcare and veterinary settings. We must continue to take new steps to slow the development of resistance and extend the usefulness of these lifesaving drugs.
Combating antimicrobial resistance continues to be a top priority for the U.S. Food and Drug Administration (FDA).
To further these efforts, the FDA will soon implement a new, five-year blueprint for how the FDA plans to build on its current programs to advance antimicrobial stewardship in veterinary settings. We’ll expand on the FDA’s existing actions, and launch some new programs. Our aim is to reduce overuse of antimicrobial drugs and combat the rising threat of resistance.
As part of the FDA’s regulatory mission, our Center for Veterinary Medicine (CVM) is responsible for ensuring the safety and effectiveness of animal drugs, including antimicrobials. CVM has already taken important steps to update the approved conditions of use for medically important antimicrobials (i.e., antimicrobials important for treating human disease) to support judicious use in food-producing animals. While important progress has been made, we know that additional work is needed to address the complex challenge of antimicrobial resistance.
At FDA, we believe that the concept of antimicrobial stewardship encompasses several important principles of judicious use. These are critical to slowing the rate at which bacteria develop resistance to antimicrobial drugs. In simple terms, we believe medically important antimicrobial drugs should only be used when necessary to treat, control or prevent disease. In addition, when such use is necessary, these antimicrobials should be used in an optimal manner. They should only be used under the oversight of a licensed veterinarian.
Among the steps that CVM has already taken, perhaps the most significant action was implementation of Guidance for Industry #213. On Jan. 3, 2017, the FDA announced that it had completed implementation of GFI #213. This was the culmination of a process launched in 2013. The goal was to transition medically important antimicrobials that are used in the feed or drinking water of food-producing animals to veterinary oversight, and to eliminate the use of these products in animals for production purposes, such as for growth promotion.
Of the 292 new animal drug applications initially affected by GFI #213, 84 were completely withdrawn. Of the remaining 208 applications, 93 applications for oral dosage form products intended for use in water were converted from over-the-counter to prescription status; while another 115 applications for products intended for use in feed were converted from over-the-counter to veterinary feed directive status. Moreover, production indications (e.g., growth promotion) were withdrawn from all 31 applications that included such indications for use.
Last year, we also published a paper proposing the use of a biomass denominator to adjust annual data on the amount of antimicrobials sold or distributed for use in food-producing animals in the U.S. This adjusted estimate is intended to provide more insight into broad shifts in the amount of antimicrobials sold for use in food-producing animals and give the FDA a more nuanced view of why sales increase or decrease over time in a manner that is specific to U.S. animal production. The agency also recently launched the Resistome Tracker. This is an interactive research and data visualization tool for antibiotic resistance genes.
To build on the progress already made, we’re announcing that the FDA will shortly publish a blueprint on how we’ll press forward and implement additional steps to address antimicrobial resistance in veterinary settings. This blueprint will serve as the FDA’s new, five-year plan. We’ll include key goals, objectives and actions that CVM will focus on during fiscal years 2019 – 2023.
Our new activities will be aimed at addressing three key goals:
Aligning antimicrobial drug product use with the principles of antimicrobial stewardship; supporting efforts to foster better stewardship of antimicrobials in veterinary settings; and enhancing the monitoring of antimicrobial resistance and antimicrobial drug use in animals.
The specific objectives and actions will be outlined in our forthcoming plan.
Some of the important issues to be addressed in this new plan include establishing appropriate durations of use of medically important antimicrobials, and bringing all dosage forms of medically important antimicrobials under veterinary oversight. We are also developing and advancing new strategies for promoting antimicrobial stewardship in companion animals.
We’ll advance these goals in new guidance that the FDA will develop with broad stakeholder input. And we’ll enhance transparency and keep the public apprised of progress being made.
For example, we’ll shortly publish a list of all medically important antimicrobials labeled for use in animals that lack a defined duration of use on their labels. We’ll keep this list updated as we work to implement a science-based approach for addressing this important issue.
We’re also advancing new strategies to improve the collection and sharing of data on antimicrobial drug use and resistance. To advance evidence-based practices, we need to make sure that the entire community has access to good information. And we need to develop a long-term strategy for implementing a practical, efficient antimicrobial use monitoring and reporting system for veterinary settings. Our plan will address new ways to advance these goals.
Many stakeholders helped make our previous efforts a success. These include the animal pharmaceutical and feed industry; veterinary organizations; animal producer organizations; consumer organizations; various local, state and federal agencies; legislators; and other key stakeholders.
I look forward to releasing this plan shortly, and continuing to work collaboratively to promote stewardship and preserve the effectiveness of antimicrobials for human and animal health.

Curcumin Extract Targets Fatty Liver Disease

New study investigating BCM-95® turmeric extract for potential as a preventive and treatment agent for Non-Alcoholic Fatty Liver (NAFLD) disease demonstrated exciting results. BCM-95 offers a potentiated delivery form of curcumin, a naturally occurring plant polyphenol. BCM-95 is a leading brand in the US curcumin supplement space, marketed by DolCas Biotech.

Inherent to the unique composition of BCM-95 is a full complement of pure curcuminoids and essential oils from turmeric, with a specific content of turmerones, ensuring high free-curcumin bioavailability.
The latest study was conducted at the Harry S. Truman Memorial Veterans Hospital in Columbia, Mo., and published on July 16, 2018, in the journal Physiological Reports. The robust 4-arm parallel-run murine study was led by Rory P. Cunningham, et al, at the University of Missouri Department of Nutrition and Exercise Physiology and examined BCM-95 across various parameters of liver function.
Specifically, the study focused on comprehensive changes occurring in NAFLD. Results demonstrated that supplemental dietary curcumin attenuated the development of NAFLD, as well as diminished its progression to the more severe Non Alcoholic steatohepatitis (NASH) in female Wistar rats, via its ability to reduce inflammation, oxidative stress, and hepatic steatosis. All three factors coexist in the pathology of Fatty Liver Disease.
The researchers suggested that curcumin’s role in reducing hepatic steatosis, as evidenced by increased protein markers of key lipogenesis enzymes (pACC/ACC) and lipid transporter ApoB100, acted to mitigate progression to NASH.
BCM-95 treatment was shown to decrease molecular markers of hepatic fibrosis and significantly reduce hepatocellular inflammation in both the treatment and prevention models, with significantly lowered serum markers of liver injury (AST and ALP).
In addition to these and other marked decreases in biochemical markers of the disease, reductions of fibroblast growth factors connected with resistance to blood glucose control by the liver in obese and overweight persons also occurred.
“A nearly two-point reduction in the NAFLD Activity Score (NAS) is quite significant for a plant-based ingredient, like BCM-95,” notes Shavon Jackson-Michel, ND, Director of Medical & Scientific Affairs at DolCas Biotech. “This is especially significant since there are few conventional treatments for NAFLD, a dysfunction believed to affect some 30% percent of the population.”
BCM-95’s uniquely bioavailable and bio-efficacy enhanced curcumin product is favored by many formulators. The 15-year-old brand is now supported by 50 studies. BCM-95 holds GRAS status and is kosher and halal certified.
DolCas Biotech, LLC, owns the worldwide brand rights of BCM-95 in a joint venture with India-based manufacturer, Arjuna Naturals Extracts, Ltd. With full oversight of BCM-95’s entire supply chain, a 15-year history of safe use, and GRAS status (as affirmed by a panel of experts and uncontested by the FDA) DolCas and Arjuna offer the industry a pure, clean, and safe raw material.

For Pfizer 1st FDA OKd Erythropoietin Stimulating Agent, No Rapid Uptake Seen

Plagued by regulatory delays, the FDA finally granted approval for Retacrit in May 2018, making it the first biosimilar erythropoietin-stimulating agent (ESA) to become available in the US market. Vifor Pharma, which also holds exclusive US commercialization rights to Roche’s Mircera, a long-acting ESA, will be responsible for Retacrit commercialization in the US dialysis setting. A survey of 202 nephrologists in June 2018 indicates a lukewarm audience with respect to Retacrit.
In general, about 45% of nephrologists are accepting that Retacrit will be equivalent to Amgen’s Epogen and Janssen’s Procrit in terms of efficacy and safety, and about 60% report being comfortable with the risk-benefit profile of biosimilar ESAs in both the dialysis and chronic kidney disease (CKD) setting. However, a growing preference for long-acting ESAs, Amgen’s Aranesp and Mircera, may present an uphill battle. Indeed, the most significant shift observed this quarter in the dialysis setting is the expansion of Mircera into small/medium dialysis organizations. Securing preferred status for Retacrit at one of the Large Dialysis Organizations, either DaVita or Fresenius Kidney Care, could catapult the brand, as was observed when Fresenius converted to Mircera in 2015. Only 15% of the surveyed nephrologists indicated they would be displeased if their primary dialysis unit converted, however, they are largely opposed to mandates requiring the switch of patients who are stable on their current ESA.
In the CKD non-dialysis (CKD-ND) setting, where ESA treatment rates are significantly lower, the dynamics are slightly different. About half of the office-based nephrologists stock ESAs in their practices, operating a “buy and bill” practice. Although Procrit has a higher share, a greater percentage of nephrologists prefer long-acting Aranesp in the CKD-ND setting, and 21% report that this preference will be a barrier to the use of Retacrit in this setting. Close to 40% of the nephrologists practicing in offices that do stock ESAs state that they will only be inclined to stock Retacrit if use is mandated by insurance companies.
The anemia market is much more tumultuous in the CKD-ND setting, where Keryx is actively promoting the new indication for Auryxia to treat iron-deficiency in non-dialysis patients. While iron utilization trends in the dialysis setting are essentially flatlined (Venofer continues to dominate, Triferic continues to languish) in the non-dialysis setting, Keryx is challenging the status quo and appears to be winning. More than half of the nephrologists report use of Auryxia for the IDA indication with robust future projections across all stages of CKD-ND. Two-thirds report that the new indication has led to increased use of the brand overall, and 46% state that they are likely to use Auryxia prior to IV iron. The availability of samples appears to be a key driver of new patient starts, and in a setting where promotion of IV and oral iron products is almost non-existent, Keryx’s active presence is strongly correlated to Auryxia uptake. Since the approval of Auryxia, a growing percentage of nephrologists are reporting a decrease in the use of IV iron.
Looking to the future, nephrologists largely agree that there is an opportunity to improve renal anemia outcomes in both the dialysis and CKD-ND settings. However, the comparative level of unmet need for new renal anemia therapies pales in comparison to the level of unmet need for agents such as Proteon Therapeutics’ vonapanitase for improved vascular access outcomes in dialysis and the need for new treatments for diabetic nephropathy in CKD-ND. Although familiarity has been steadily rising for the HIF-PH inhibitors (AZ/Astellas/Fibrogen’s roxadustat, Akebia/Otsuka’s vadadustat, and GSK’s daprodustat), only 12% selected one of these agents as the most desired pipeline agent. Early expectations suggest that many nephrologists expect the HIFs to have a safety advantage over ESAs, to be priced at a premium to ESAs, and to largely be used in populations not eligible for ESA treatment. A stronger market access position, in terms of formulary status at dialysis units, insurance coverage, and out-of-pocket costs, may be the deciding factor as to which HIF dominates, as presently the agents are viewed as largely interchangeable. The recently announced merger between Keryx and Akebia creates a potential competitive commercial advantage for vadadustat. In leveraging the growing momentum and existing commercial structure for Auryxia, the combined force has the unique opportunity to position iron therapy alongside HIF-PH therapy, and companies with “renal know-how” tend to fare well in this highly promotion-sensitive specialty.
RealTime Dynamix™: Renal Anemia (US) is an independent report series published on a quarterly basis. The series provides a close-quarters analysis of key performance metrics, focusing on brand gains and losses, industry contact rates, familiarity and adoption rates of recently launched products and awareness of products in development. The next quarterly update will be released in September.

Shire’s Sales Up Ahead of Takeda Acquisition

As its acquisition by Takeda Pharmaceutical edges closer and closer, Shire reported a solid second-quarter.
Shire reported $3.809 billion in product sales, an increase of six percent, and total revenues for the quarter of $3.920 billion, an increase of five percent. Operating income from continuing operations was $830 million, an increase of 108 percent, while non-GAAP operating income was flat at $1.492 billion. Net income was up 156 percent to $616 million.
“Shire continued to deliver on its key priorities of commercial execution, pipeline advancement, debt pay-down, and portfolio optimization during the second quarter,” said Flemming Ornskov, Shire’s chief executive officer, in a statement. “We drove product sales growth of six percent over the prior year period led by the strong performance of our Immunology franchise, continued uptake of our recently launched products, and expansion in international markets.”
Reuters notes, “Earlier on Tuesday, Takeda said its first-quarter operating profit had halved from a year ago, when it had booked gains from asset sales. It is buying Shire to broaden its drugs portfolio and plug a gap in its late-stage pipeline.”
The acquisition deal was officially made on May 8, with Takeda buying Shire for $62.2 billion. Earlier in the deal process, Shire sold its oncology business to France’s Servier for $2.4 billion. Oncology was a small part of Shire’s portfolio, bringing in about $262 million in 2017. The sale of the oncology business was unrelated to the Takeda acquisition bid.
The combined companies will have headquarters in Japan. Takeda shareholders will own about 50 percent of the merged companies. The two companies will have a combined workforce of about 52,000 people worldwide. The merged companies have projected job cuts of six to seven percent, which means cuts in the low to mid-3,000s. In addition, Takeda is considering consolidating Shire’s operations into its own in Boston, Switzerland and Singapore.
A small group of Takeda shareholders was attempting to halt the acquisition, but their bid didn’t gain traction. A group of 130 Takeda shareholders felt Takeda was taking on too much debt to pull off the deal, and it wasn’t worth it. At the annual general meeting in June, the group put their proposal to a vote, asking that advance shareholder approval be required for large acquisitions. Their proposal received about 10 percent of votes in favor, which was unlikely to lead to stopping the Shire acquisition.
In today’s announcement, Ornskov also stated, “During the quarter, our Board reached an agreement with the Takeda Board on the terms of a recommended offer for Takeda to acquire Shire. The acquisition is expected to close in H1 2019, subject to shareholder approval of both companies and additional regulatory approvals. In the meantime, we remain resolutely focused on execution as these results demonstrate.”
Shire also gave a pipeline update, noting that the U.S. Food and Drug Administration (FDA)approved Cinryze for pediatric use and the European Medicines Agency (EMA)’s Committee for Medicinal Products for Human Use (CHMP) recommended marketing authorization for Veyvondi in Europe. Ornskov added, “In addition, we gained U.S. FDA approval for our state-of-the-art plasma manufacturing facility near Covington, Georgia supporting the continued growth of our immunoglobulin portfolio.”

Sanofi Q2 Sales Down, but Plans to Fix Diabetes Division

For its second-quarter financial report, Paris-based Sanofi reported a decrease in net sales for the quarter of 5.7 percent, down to 8.176 billion euros. Sanofi Genzyme sales grew 14.1 percent, driven by Dupixent and consolidation of Bioverativ, which it acquired earlier this year. Bioverativ was a spinoff from Biogen. Bioverativ spun off from Biogen’s hemophilia unit in January 2017. Sanofi bought it for $11.6 billion in January 2018.
The company’s second-quarter earnings per share (EPS) rose 1.5 percent to 1.25 euros. Its Emerging Market sales grew 5.2 percent, with double-digit growth in China.
“In the second quarter, we achieved significant milestones in building our new rare Blood Disorder franchise and the successful continued execution of the global roll-out of Dupixent,” said Olivier Brandicourt, Sanofi’s chief executive officer, in a statement. “As the impact from the U.S. losses of exclusivity peaked in the second quarter, the growth of our diversified businesses largely compensated for these headwinds. We look forward to entering a new growth phase led by our increasing focus on Specialty Care and our leadership positions in Emerging Markets and Vaccines.”
Sanofi’s diabetes and cardiovascular franchises, however, which have struggled in the U.S. after it lost exclusivity for insulin drug Lantus, had a 9.4 percent on-year decline. Earlier this month, Sanofi told Dow Jones Newswires that it is attempting to convince intermediaries, particularly in the U.S., to approach its insulin products in a different way, in order to increase sales. It’s not clear if that will help since most companies in the diabetes market are struggling with U.S. pricing for insulin-related products.
MarketWatch writes, “On Tuesday the company again declined to specify which intermediaries it has been in talks with, as formulary decisions haven’t yet been announced. But a company spokesman confirmed that Medicare bids for 2019 have been submitted, with decisions expected in October. The company also confirmed that data from the Bright study, which has informed Sanofi’s new insulin unbundling strategy, will be presented to Medicare, but declined to comment on whether Medicare bundles its insulins.”
Overall, Sanofi Genzyme (Specialty Care) reported 14.1 percent growth, Sanofi Pasteur (Vaccines) reported a decrease of 15.7 percent, Diabetes & Cardiovascular reported a drop of 15.6 percent, Consumer Healthcare grew by 4.1 percent, and General Medicines & Emerging Markets dropped 3.7 percent.
In the quarterly conference call, Brandicourt indicated Sanofi is positioning itself for a new phase of growth. And with both its acquisition of Bioverativ and Ablynx, both in January, the company shows a heavy push into blood disorders. Ablynx’s most advanced pipeline product is caplacizumab for the treatment of acquired thrombotic thrombocytopenic purpura (aTTP).
PMLive notes, “A bright point was the rare blood disorder business bolted on with the $11.6 billion acquisition of Bioverativ, up 15.5 percent on a pro forma basis to 257 million euros, and Sanofi is hoping that the 3.9 billion euro takeover of antibody specialist Ablynx and lead rare disease drug caplacizumab will also pay off in the years to come.”

United Therapeutics: FDA approves implantable system application

United Therapeutics (UTHR) announced approval by the FDA of a new drug application, or NDA, for the use of Remodulin injection in the Implantable System for Remodulin, or ISR. The ISR has been developed under a collaboration with Medtronic (MDT). In December 2017, Medtronic received FDA approval of a premarket application, or PMA, for a proprietary intravascular infusion catheter to be used with its SynchroMed II implantable infusion pump and related infusion system components in order to deliver Remodulin for the treatment of pulmonary arterial hypertension, or PAH. Remodulin was originally approved by the FDA to treat PAH by continuous subcutaneous and intravenous routes of administration in 2002 and 2004, respectively, using external pumps. In the case of intravenous users, the therapy can be very burdensome and brings a risk of sepsis due to the use of a central indwelling catheter. The ISR provides patients a new option for delivery of intravenous Remodulin, where the entire delivery system is implanted into the body and will be refilled by healthcare professionals at intervals of up to 16 weeks depending on the patient’s dose, using a syringe needle through the patient’s skin.

Bristol-Myers: EC approves Opdivo for treatment of adults with melanoma

Bristol-Myers Squibb announced that the European Commission has approved Opdivo for the adjuvant treatment of adult patients with melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection. This indication is for both BRAF mutant and wild-type melanoma patients. With this decision, Opdivo becomes the first and only PD-1 therapy to receive an EC approval in the adjuvant setting and has gained its eighth indication across six distinct tumor types in the European Union.

Illumina price target raised to $330 from $280 at Deutsche Bank

Deutsche Bank analyst Dan Leonard raised his price target for Illumina to $330 saying the “strong beat” in Q2 on stronger NovaSeq demand supports his thesis. The analyst sees upside for estimates over the next 6-12 months and reiterates a Buy rating on the shares.

Novocure announces published results of Phase 2 ovarian cancer med trial

Novocure announced that the results of its INNOVATE phase 2 pilot trial have been published in Gynecologic Oncology. The INNOVATE trial was a prospective, single-arm study testing the feasibility, safety and preliminary efficacy of Tumor Treating Fields combined with weekly paclitaxel in recurrent ovarian cancer. Tumor Treating Fields is a cancer therapy that uses electric fields tuned to specific frequencies to disrupt cell division, inhibiting tumor growth and causing affected cancer cells to die. Progression free survival of recurrent ovarian cancer patients treated with Tumor Treating Fields plus weekly paclitaxel was more than double that of weekly paclitaxel-treated historical controls. Median progression free survival in the Tumor Treating Fields-treated group was 8.9 months and median overall survival was not yet reached. Median one-year survival in the Tumor Treating Fields-treated group was 61%. The median compliance of patients with Tumor Treating Fields in the first three months of treatment was 77%. Two cases of severe skin irritation due to Tumor Treating Fields were reported. No other serious device-related adverse events were reported.

NuVasive cuts FY18 adjusted EPS view to $2.37-$2.40 from $2.44-$2.47

FY18 consensus $2.44

NewLink Genetics announces organizational changes

The company has completed an organizational realignment that will support these clinical development efforts within its current financial capacity, substantially cut future expenses, and extend its cash runway into the second half of 2021.The organizational changes include a reduction in headcount of approximately 30%, and include the following changes to senior leadership, effective immediately:Jack Henneman has been appointed Chief Administrative Officer for a transition period to end with his retirement from NewLink in November 2018;Carl Langren has been promoted to Chief Financial Officer; Lori Lawley has been promoted to Vice President, Finance and Controller; Brad Powers has been promoted to General Counsel.

Universal Health acquires The Danshell Group, terms not disclosed

Universal Health Services announced that, through its UK subsidiary Cygnet Health Care, it has acquired The Danshell Group. Danshell owns and operates 25 facilities with a total of 288 beds in the United Kingdom. Cygnet Health Care will operate and manage these new facilities. The Danshell facilities support and care for adults living with learning disabilities, who may also have a diagnosis of autism, in specialist supported living, residential services and hospitals. Through this acquisition, the company expands into new service lines and new geographical areas, complementary to the existing UK portfolio.

Emergent BioSolutions Initiates Phase 1 Study of Zika Virus Therapeutic

  • ZIKV-IG granted Fast Track designation by the U.S. Food and Drug Administration
Emergent BioSolutions Inc. EBS, +2.57% today announced the initiation of a Phase 1 clinical study to evaluate the safety and pharmacokinetics of ZIKV-IG, the company’s anti-Zika virus immune globulin, being developed as a therapeutic intervention against Zika virus disease. ZIKV-IG was granted Fast Track designation by the U.S. Food and Drug Administration (FDA) in December 2017.
“Zika is an important disease with global impact due to its profound effect on the fetus and child-maternal health,” said Dr. Laura Saward, senior vice president and antibody therapeutics business unit head at Emergent BioSolutions. “The World Health Organization has stated the urgent need for accelerated research and development for countermeasures for Zika given its potential to cause a public health emergency and the absence of efficacious drugs and vaccines for the disease. Emergent is focused on providing preparedness solutions that address public health threats and emerging infectious diseases. Our program, initiated in 2017, seeks to accelerate development of a Zika-specific immune globulin that leverages our proven platform technology, four decades of patient experience with hyperimmunes, and core competencies in advanced development and manufacturing.”
The FDA’s fast track process is designed to facilitate the development and expeditious review of products to treat serious conditions and fill an unmet medical need. The main purpose is to get important new drugs to the patient earlier. A drug that receives Fast Track designation could mean more frequent meetings and/or communications between the sponsor and FDA, eligibility for priority review of a Biologics License Application (BLA) if relevant criteria are met, and/or a rolling BLA submission, which allows FDA to review sections of the BLA in advance of receiving the complete submission.
ZIKV-IG is a purified human immunoglobulin containing neutralizing antibodies to Zika virus. It is being developed on the company’s human hyperimmune platform, on which several marketed antibody therapeutics have been licensed, including Emergent’s Anthrasil [(R)] [Anthrax Immune Globulin Intravenous (Human)] and VIG [Vaccinia Immune Globulin Intravenous (Human)] (VIGIV) products.
This Phase 1 double-blind, randomized, placebo-controlled clinical study will enroll approximately 30 healthy volunteers at a single site.

Progenics price target raised to $16 from $14 at Needham

Needham analyst Chad Messer raised his price target on Progenics to $16 after the FDA approved Azedra for intravenous use for certain types of locally advanced or metastatic pheochromocytoma or paraganglioma who require systemic anticancer therapy. Messer keeps a Strong Buy rating on Progenics shares.

Sienna has bigger value drivers than SNA-001 in acne, says BMO Capital

BMO Capital analyst Gary Nachman called Sienna Biopharmaceuticals’ announcement that SNA-001 failed in two of its three pivotal studies in acne an “unfortunate outcome,” but he believes the bigger long-term value drivers for Sienna remain SNA-001 for light-hair removal and SNA-125 for psoriasis and atopic dermatitis. After removing any SNA-001 acne revenue from his estimates, Nachman lowered his price target on Sienna Biopharmaceuticals to $27 from $30 and keeps an Outperform rating on the shares

Pfizer CEO sees Trump eliminating drug rebates

Pfizer CEO Ian Read said he believes the Trump administration plans to stop the practice of allowing rebates on prescription drug purchases, indicating that U.S. drug pricing reforms may focus on middlemen instead of drug makers, Reuters reports. “I believe the administration does want to remove rebates, and they consider it a priority,” Read said in an interview

Greenlight shorting Athenahealth again after recent spike

Greenlight says the activist involved with Athenahealth has “little interest” in buying the company, according to Bloomberg.

Prevent the number one cause of accidental child death

Last month, Olympic skier Bode Miller and his wife, Morgan, lost their 19-month-old daughter, Emeline, after she drowned in a neighbor’s pool.
Now the couple is determined to raise awareness about child drowning, which is the leading cause of unintentional deaths for children 1 to 4 years old, according to a report by the Consumer Product Safety Commission.
Three hundred fifty-one children younger than 15 died in pool or spa-related drownings per year, between 2013 and 2015, according to a report by the organization.
The best way to prevent these accidents is to ensure that pools have four-sided fencing, including fencing between the pool and the door that leads to it, Philip Patrick Mularoni, the medical director of the Pediatric Sports Medicine Division at Johns Hopkins, tells The Post.
“When a child is in or near the pool, an adult should always be within reach of the child,” says Mularoni, who’s based in St. Petersburg, Fla. “And someone should be designated to watch the child or children, in case other adults get distracted.”