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Wednesday, July 4, 2018

Sessions: Reversing Obama rules promoting college admission ‘diversity’


Attorney General Jeff Sessions on Tuesday rescinded a series of Obama-era guidelines aimed at promoting diversity in higher education.
The documents laid out legal guidelines for how colleges could properly consider race in admissions decisions in order to promote campus diversity. Rescinding the guidelines does not change official U.S. policy, but marks a return to the George W. Bush-era approach of “race-neutral” college admissions.
The guidelines were among 24 that Sessions pulled back on Tuesday, deeming them “unnecessary, outdated, inconsistent with existing law, or otherwise improper.”
The Trump administration has argued that the rules violate Supreme Court precedent on affirmative action.
“The Supreme Court has determined what affirmative-action policies are constitutional, and the Court’s written decisions are the best guide for navigating this complex issue,” said Education Secretary Betsy DeVos in a statement.
The move has been harshly criticized by civil rights groups, who say that rescinding the guidances will be detrimental to students of color in the U.S.
The American Council on Education has already vowed to ignore the decision, saying that the administration is sending “precisely the wrong message” to institutions of higher education.
But Sessions argued that the decision to rescind the policies was intended to undo what he described as government overreach and previous administrations’ efforts to “impose new rules on the American people without any public notice or comment period, simply by sending a letter or posting a guidance document on a website.”
“That’s wrong, and it’s not good government,” he said.
Still, abandoning the Justice Department guidelines does not change current U.S. law, and schools are allowed to operate as they choose, so long as their actions fit within existing legal precedents.
The move came days after Justice Anthony Kennedy announced that he would retire from the Supreme Court this summer. His departure means that the court will lose a key swing vote on affirmative action issues, while allowing President Trump to nominate a more conservative replacement.
Affirmative action in college admissions is the subject of one high-profile lawsuit alleging that Harvard University has discriminated against Asian-American applicants in order to free up spots for other racial minorities.
The Justice Department weighed in on the side of the Asian-American applicants in April, asking a federal judge to order the release of years of Harvard admission records.

Exelixis says Celestial Phase 3 results published in NEJM


Exelixis announced that The New England Journal of Medicine published results from the Celestial Phase 3 pivotal trial of cabozantinib in patients with previously treated advanced hepatocellular carcinoma.1 The data, originally presented at the 2018 American Society of Clinical Oncology’s Gastrointestinal Cancers Symposium in January, demonstrate that cabozantinib provided a statistically significant and clinically meaningful improvement in overall survival versus placebo, the company said in a statement. Median overall survival in Celestial was 10.2 months with cabozantinib versus 8.0 months with placebo. Median progression-free survival was more than doubled, at 5.2 months with cabozantinib and 1.9 months with placebo. “Patients with this form of advanced liver cancer have very limited treatment options once their disease progresses following treatment with sorafenib,” said Ghassan K. Abou-Alfa, M.D., Memorial Sloan Kettering Cancer Center, New York and lead investigator on Celestial. “These results suggest that, if approved, cabozantinib could become an important addition to the treatment landscape that may help slow disease progression and, critically, improve survival for these patients.”

Alnylam says Apollo Phase 3 trial of patisiran published in NEJM


Alnylam Pharmaceuticals announced that the pivotal study results from the Apollo Phase 3 trial of patisiran were published online today in The New England Journal of Medicine. The study showed that patisiran improved measures of polyneuropathy, quality of life, activities of daily living, ambulation, nutritional status, and autonomic symptoms relative to placebo in patients with hereditary transthyretin-mediated amyloidosis, the company said. Patisiran treatment also led to favorable effects on exploratory endpoints related to cardiac structure and function in patients with cardiac involvement, it added. Further, the frequency and severity of adverse events were similar in patients receiving patisiran and placebo, with the exception of peripheral edema and infusion-related events which were higher in patisiran-treated patients and generally mild to moderate in severity. “We are extremely pleased with the publication of this landmark manuscript, the first-ever pivotal RNAi clinical trial to be published in a top-tier, peer-reviewed medical journal,” said Akshay Vaishnaw, President of Research and Development at Alnylam

CMS Seeks to Simplify Home Health Recertifications


Physicians would no longer have to predict how much longer a particular Medicare patient will need homecare in order to have the service re-certified, according to a regulation proposed Monday by the Centers for Medicare & Medicaid Services (CMS).
“In an effort to make improvements to the health care delivery system and to reduce unnecessary burdens for physicians, CMS is proposing to eliminate the requirement that the certifying physician estimate how much longer skilled services are required when recertifying the need for continued home health care,” the agency said in a fact sheetabout the proposed rule.
“This proposal is responsive to industry concerns about regulatory burden reduction and could reduce claims denials that solely result from an estimation missing from the recertification statement. We estimate that this proposal would result in annualized cost savings to certifying physicians of $14 million beginning in [calendar year] 2019.”
In addition to eliminating that requirement, “we’re releasing several proposals to modernize Medicare by increasing access to remote patient monitoring,” CMS administrator Seema Verma said Monday on a phone call with reporters.
“This will allow more patients to share real-time data [with providers]. Last year we made changes to allow physicians to bill for remote patient monitoring,” she said. “Home health agencies, however, couldn’t bill for the new code. So in today’s proposal we address that disparity.”
CMS also is beginning to implement a new home infusion therapy benefit — using a transitional payment until the full benefit takes effect in 2021 — and proposing health and safety standards for home infusion therapy.
The rule also removes seven measures for the home health quality reporting program that were either unnecessary or “topped out” — that is, everyone was doing extremely well on them so there was no need to continue measuring them, Verma explained. Contrary to messages released by some groups, “none of the measures we’re eliminating will reduce transparency or patient safety,” she added, noting that the burden reduction achieved by eliminating the measures is expected to result in a net savings of $60 million.
In addition, CMS is proposing to remove five outcome measures from its Home Health Value-Based Payment model currently used for reimbursement:
  • Influenza Immunization Received for Current Flu Season
  • Pneumococcal Polysaccharide Vaccine Ever Received
  • Improvement in Ambulation-Locomotion
  • Improvement in Bed Transferring
  • Improvement in Bathing
The agency also plans to add two proposed composite outcome measures: Total Change in Self-Care and Total Change in Mobility.
Looking ahead to 2020, Verma noted that Congress has mandated the agency stop using the number of therapy visits made to determine payments “because some patients have complex needs that don’t involve a lot of therapy…. We’ve proposed a Patient-Driven Groupings model that is relying more heavily on clinical characteristics to determined the amount of payment and eliminate the use of the therapy threshold.”
Not everyone is happy with that idea, however. “It appears that the 2020 model is a modestly adjusted and “warmed-over” version of the highly criticized Home Health Groupings Model [HHGM] re-labeled as the Patient-Driven Groupings Model,” William Dombi, president of the National Association for Home Care & Hospice (NAHC), said in a statement. “Many of the same weaknesses present in HHGM exist in this new version.”
“NAHC remains very concerned that the new model still includes a significant ‘behavioral adjustment’ based on assumptions that would trigger a 6.42% reduction in base payment rates,” he continued. “Many of these assumptions are driven by CMS’s design with unnecessary changes to the current model.”
“We do not want to prematurely judge the 2020 version of payment reform as it is complex, detailed, and will require deep analysis,” Dombi said. “However, we are concerned that CMS may have been relegated to using too much from its HHGM design because CMS is pressed by a deadline. We hope that Congress can recognize the value of providing a more flexible timeframe to CMS.”
“We will be addressing all of our concerns with CMS through the rulemaking process and enlisting Congressional support as needed to develop reasonable payment reform,” he concluded. “These proposals … warrant close and critical review by the industry before any judgment is made. Still, an early review indicates that the proposed system needs more work.”
The proposed rule is open for comment until 5 p.m. on Aug. 31. CMS is also is expected to release payment rules for other providers, including the physician payment rule, in the coming days.

Cancer Linked to Infertility in Men and Women


Men treated for infertility with intracytoplasmic sperm injection (ICSI) had a significantly increased risk of early-onset prostate cancer, according to data from several large registries.
Use of ICSI to facilitate conception was associated with a 47% higher risk of prostate cancer as compared with men who conceived naturally. Analysis of cancer cases by age at diagnosis showed that men who underwent ICSI had almost a three-fold greater risk of developing prostate cancer before age 50 but not at older ages.
Despite the association with ICSI, the results did not implicate ICSI as the causative factor in early-onset prostate cancer, reported Yahia Al-Jebari, of Lund University in Sweden, and colleagues at the European Society of Human Reproduction and Embryology (ESHRE) meeting in Barcelona. Instead, the study added to existing evidence of an association between impaired sperm production and an increased risk of prostate cancer.
“The increased risk of prostate cancer is definitely not because of the ICSI treatment per se, which we know has no biological impact on the male,” Al-Jebari said in a statement. “In Sweden, ICSI is reserved for men who cannot conceive through in vitro fertilization (IVF), and we would expect most fertile men having fertility treatments to be in the IVF group. So in this study, the ICSI fathers are highly selected and generally have very poor semen quality.”
A separate ESHRE study suggested that infertility in women increases the risk of ovarian cancer, but that ovarian stimulation associated with IVF is not to blame, reported Anja Pinborg, MD, of Copenhagen University Hospital in Denmark.
ICSI and Prostate Ca
Previous studies yielded inconsistent data regarding the association between male infertility and prostate cancer. Registry-based studies showed a lower risk of prostate cancer among childless men as compared with men who were biological fathers, Al-Jebari’s group noted. Other studies suggested that men with impaired fertility have an increased risk of prostate cancer as compared with fertile men.
To continue investigation of male infertility and prostate cancer, researchers analyzed data from birth, assisted reproduction, and cancer registries in Sweden. They identified all men who fathered children from 1994-2014 and compared those who conceived with the aid of ICSI or IVF versus men who conceived naturally. Follow-up continued to 2016.
The analysis included 1.2 million men, 52 million person-years of follow-up, and 3,211 prostate cancer diagnoses. The data showed that men who had undergone ICSI had a 47% increase in the hazard for prostate cancer versus the control group (95% CI 1.15 to 1.89, P=0.002). Conception via IVF did not increase the risk of prostate cancer versus natural conception (HR 1.14, 95% CI 0.91 to 1.43, P=0.25).
Stratification of the cancers by age at diagnosis showed that conception with the aid of ICSI increased the hazard for prostate cancer diagnosis before age 50 to 2.94 versus the control group (95% CI 1.84 to 4.71, P<0.001). ICSI was not associated with an increased risk of later-onset prostate cancer. After excluding men whose prostate cancer diagnosis occurred before conception, the hazard for prostate cancer remained elevated, overall (HR 1.32, 95% CI 1.01 to 1.72, P=0.045) and for early-onset disease (HR 2.54, 95% CI 1.52 to 4.24, P<0.001).
Al-Jebari acknowledged that relatively few men in the ICSI group developed prostate cancer (n=63) and that the trial did not include comparisons with men who had never fathered children.
IVF and Ovarian Ca
The study of IVF and ovarian cancer had its origin in a hypothesized association of the risk-increasing effect of IVF. Previous studies led to conflicting findings, Pinborg’s group noted. Further confounding the issue, several studies showed that nulliparous women have an increased risk of ovarian cancer.
In an attempt to clarify the relationship between IVF and ovarian cancer, investigators analyzed data from the Danish National ART-Couple II (DANAC II) cohort, which includes all women receiving assisted reproductive technology (ART) in Denmark from 1994-2015. Each DANAC II woman was matched by age with 10 women with no history of ART. Follow-up in both groups continued until a first cancer diagnosis, death, loss to follow-up or Dec. 31, 2015.
Data analysis included 58,472 women who received ART and 549,210 who did not. Both groups had a low incidence of ovarian cancer, which was nonetheless higher in the women who had received ART (0.11% vs 0.06%, HR 1.20, 95% CI 1.10 to 1.31).
Subgroup analysis showed that female-origin infertility was associated with an ovarian cancer incidence in nulliparous women (HR 2.38, 95% CI 2.17 to 2.60) similar to that of nulliparous women in the non-ART control group (HR 2.03, 95% CI 1.89 to 2.19). ART for male-factor infertility or unexplained causes was associated with a reduced risk of ovarian cancer (HR 0.87, 95% CI 0.76 to 1.00).
ART’s association with excess ovarian cancer risk reached a peak in the first 2 years after initiation of treatment and disappeared altogether after 12 years, suggesting possible detection bias during ART treatment.
Calling the data reassuring, Pinborg said in a statement, “I would advise infertile women contemplating ART treatment to go ahead. Ovarian stimulation itself is not introducing any excess risk of ovarian cancer.”
Al-Jebari, Vassard, and co-authors disclosed no relevant relationships with industry.
LAST UPDATED 

Patients Often Mistake Migraine ‘Triggers’


Chocolate and other foods commonly thought to trigger migraine were found to have little relationship to headache onset when patients kept systematic track, according to several studies presented here.
Study participants used a web interface or smartphone app to record their food consumption and timing of headaches, allowing researchers to analyze patterns of association. One analysis looked at headache occurrence on weekdays versus weekends.
These findings were presented at the American Headache Society (AHS) annual meeting. The conference also featured an expert debate about whether people prone to migraine should always avoid potential triggers.
A wide range of factors are thought to trigger migraine headache. Some, such as stress, lack of sleep, and hormonal fluctuations, are supported by considerable evidence. Others, such as specific food items, are more anecdotal and research has yielded mixed results. Digital tools that make it easier for patients to record their experience can help shed light on suspected associations.
“We know that migraine and its triggers differ for every person,” said AHS scientific program committee chair Peter Goadsby, MD, PhD, of King’s College London. “These data will hopefully help healthcare providers when evaluating the lifestyle and experiential factors of an individual patient’s life.”
Chocolate and Other Triggers
Stephen Donoghue, PhD, of N1-Headache, formerly known as Curelator Headache, and colleagues presented a series of posters describing studies looking at the links between suspected triggers and migraine occurrence.
Patients with migraine used the Curelator Headache digital platform, available through a web interface or an iPhone app, to answer questions about more than 70 migraine-related factors. A total of 774 people tracked these factors and the occurrence of headaches daily for at least 90 days. More than 80% were women and the mean age was 43 years.
Just over half of the participants (53.7%) said that chocolate was a suspected trigger, with 27.0% saying it had a mild effect (1-3 on a 10-point scale), 14.6% rating it had a moderate effect (4-6), and 12.0% saying it was a strong factor (7-10); 46.3% said they did not suspect chocolate as a trigger.
Among the 606 participants who entered enough data for analysis, chocolate was found to be associated with an increased risk of headache attacks for 10 people (1.7%) and a decreased risk for 16 people (2.6%), with no association noted for the remaining 580 people (95.7%).
About one in five participants did not enter enough data, reported too little or insufficient variability in their chocolate consumption, or had too few or too many migraine attacks to allow for reliable analysis.
“Chocolate is certainly not a common trigger,” the investigators concluded. “It is probable that the low levels of association for both increased and decreased attack risk are simply stochastic. Nevertheless, we cannot rule out that chocolate may be a trigger for some people and a protector for others — but they would be the exception rather than the rule.”
Results were generally similar for nitrates, used as a preservative for foods such as processed meats, and the food additive monosodium glutamate (MSG).
A total of 347 participants (47.5%) suspected nitrate as a migraine trigger, while 384 (52.5%) did not. Among the 370 people who entered enough data for analysis, nitrates were shown to be associated with increased headache risk for 10 people (2.7%), decreased risk for five people (1.4%), and no association was seen for 355 people (95.9%).
Likewise, 385 (52.6%) suspected MSG as a triggering factor, while 347 (47.4%) did not. Among the 227 people with analyzable data, MSG was found to be associated with increased risk for seven people (3.1%), decreased risk for two people (0.9%), and no association for 218 people (96.0%).
For both nitrates and MSG, more than half of study participants did not enter enough data or were not analyzable for various reasons.
For all three triggers, the researchers noted that there was no clear link between the degree of suspicion and the likelihood of identifying an association. Many people reported no consumption of chocolate, nitrates, or MSG, which the researchers suggested might indicate avoidance of a suspected trigger.
“Contrary to the widespread expectations of our users, the data reveals that foods containing chocolate, MSG, and nitrates are rarely associated with migraine attacks and surprisingly, for a minority of individuals, they may be associated with a lower risk of attack,” N1-Headache founder and CEO Alec Mian, PhD, said in a company press release.
The investigators also looked at the association between type of day — weekday or weekend — and migraine occurrence. Among the 707 participants eligible for this analysis, 26 (3.7%) had an increased risk of headache attacks on non-work days, 10 (1.4%) had a decreased risk, and 623 (88.1%) had no identifiable association.
“The concept of ‘weekend headache’ is widely accepted among clinicians and patients, yet clinical trials to date have yielded conflicting results which neither confirm nor deny the presence of this headache pattern,” the researchers concluded. “For almost all subjects in this study, the risk of migraine did not differ on work days compared to days off and holidays.”
Triggers: To Avoid or Not to Avoid
During the debate on migraine triggers, Richard Lipton, MD, of Albert Einstein College of Medicine in New York City, took the “should avoid all triggers” position, noting that these can be highly variable across individuals.
His opponent, Paul Martin of Australian National University in Canberra, countered that there are so many purported migraine triggers, and they are so ubiquitous, that is futile to try to avoid them all at all times — and trying to do so can actually increase anxiety. Instead, people with migraines should receive help to cope with triggers.
During a media briefing in advance of the meeting, Goadsby suggested a new way of thinking about migraine triggers.
“What we’re learning by studying the premonitory phase that occurs in the days or hours before the attack, when the patient will feel tired or get a bit moody or crave sweet or savory things, is that the brain has actually started to have the attack,” he told reporters. “Chocolate is an excellent example. When the brain drives you to take some chocolate and a day and a half later you get migraine, the association is absolutely correct, but the causality is different — the mechanism has already started.”
“What we’re learning from the diary work is that while you can recommend general regularity, an individual needs to ask themselves whether what they’re calling a trigger is actually the beginning of their attack. That releases them from the punishment of worrying about the trigger and gives them information about what is about to happen,” Goadsby continued. “Obviously, if you feel you’re in the premonitory phase that is not a night to go out, to stay up late, to find your favorite alcohol. It’s a night to be careful, to look after yourself, to prepare for the next day. This understanding is going to empower patients to get better control.”
Donoghue and Mian are employees of N1-Headache. Goadsby and Lipton reported relationships with numerous companies active in migraine drug development. Martin reported no relevant disclosures.

Hong Kong exchange picks up steam with two biotech IPOs from Innovent, MicuRx


Amid the IPO frenzy taking place on the Nasdaq, the stock exchange in Hong Kong has quietly caught up with two applications at the end of last week — the third and fourth companies to try the route since the city opened up to pre-revenue biotechs wanting to list.

The first candidate is Innovent Biologics, a 7-year-old biotech unicorn long rumored to be angling for a public listing and handed $150 million in a Series E crossover round weeks ago. They were joined by fellow Shanghai-based drugmaker MicuRx Pharma, which is looking for some help powering through various studies for its drugs treating multiple drug resistant infections.
In an unusual chairman’s letter that starts off the application document, Innovent founder and CEO Michael Yu reflected on the founding philosophy of the company:
The reality is that there is a huge gap between China’s biopharmaceutical industry and international standards. China’s biopharmaceutical production capacity is less than one-fiftieth of that of the United States, and not even one-tenth of that of South Korea. Among the top ten best-selling drugs in the world, eight are biologics and five are monoclonal antibody drugs, while China’s bestselling drugs are still mostly chemical drugs and traditional Chinese medicines. Imported drugs dominate China’s antibody drug market, and for most Chinese patients, these life-saving drugs are often unaffordable and out of reach.
His answer to that need has now grown to a 510-strong company with a pipeline of 17 drugs, with seven in clinical development and four in Phase III trials.
Sintilimab, a PD-1 inhibitor currently under priority review in China, is the star here; Innovent is also looking to start early-stage trials of the drug in the US while using it as a base for two other assets they are co-developing with Eli Lilly.
As is standard in these applications, Innovent redacted anything that could remotely give the IPO away, so we don’t know whether it is indeed seeking $300 million to $500 million, as Reuters previously reported. What we do know is that sintilimab, together with three biosimilars — going after blockbusters like Avastin, Rituxan and Humira — will claim most of the raise, from trials and registration filings to commercialization.
Great Biono Fortune, a coalition of Innovent employees, owns the largest chunk of stock at 10.22%, followed by Lilly Asia Ventures and F-Prime Capital, which have 8.86% each.

MicuRx, meanwhile, has kept its ambitions tightly under wraps. CEO Zhengyu Yuan founded the company after an R&D stint at Vicuron (merged with Pfizer) with the help of then-colleague Mike Gordeev, now CSO.
The company, which has teams in both San Francisco and Shanghai, closed a $15 million financing last year to complete a Phase III for its lead oral antibiotic, contezolid (MRX-1). The bulk of the raise will go toward MRX-4, a prodrug formulation of MRX-1 dubbed contezolid acefosamil. While the drug is only beginning human studies in China, it’s ready to roll with a Phase II in the US later in the year. MicuRx will also invest some cash into a preclinical polymicin antibiotic backed by CARB-X.
A BVCF subsidiary and Morningside are the largest shareholders, controlling 29.12% and 26.50% respectively.