| DATE | COMPANY NAME | AMOUNT (USD) | COMPANY HQ | RESEARCH FOCUS |
|---|---|---|---|---|
| 1/18/19 | Avedro | $86M Filed | Waltham, MA | Technology for corneal ectatic disorders and refractive conditions |
| 1/15/19 | INmune Bio | $20M Priced | La Jolla, CA | Modulate innate immune system to respond to cancer |
| 1/14/19 | Brainsway | $30M Filed | Jerusalem, Israel | Deep TMS technology for the treatment of MDD and OCD |
| 1/11/19 | Cirius Therapeutics | $86M Filed | San Diego, CA | Innovative therapies for the treatment of liver and metabolic diseases |
| 1/11/19 | Kaleido Biosciences | $100M Filed | Lexington, MA | Modulate the metabolic output and profile of the body’s microbiome |
| 1/7/19 | Alector | $150M Filed | San Francisco, CA | Develop therapies that empower the immune system to cure neurodegeneration |
| 1/7/19 | Anchiano Therapeutics | $35M Filed | Jerusalem, Israel | Genetic therapy for early-stage bladder cancer |
| 1/4/19 | Poseida Therapeutics | $115M Priced | San Diego, CA | CAR-T products to treat hematological malignancies and solid tumors |
| 1/4/19 | China SXT Pharmaceuticals | $10.2M Priced | Taizhou, China | Research, development, manufacture, marketing and sales of Traditional Chinese Medicine Pieces |
Monday, January 21, 2019
January 2019 Life Science IPOs
Intermittent Fasting Plus Lower-Calorie Diet May Be Best
Overweight women who ate a lower-calorie diet and fasted 3 days a week lost more weight and had better cardiometabolic markers than women who only reduced their calorie intake, or only fasted, or did neither in a small, 8-week randomized trial.
“Obese women who followed a diet in which they ate 70% of their required energy intake and fasted intermittently lost the most weight,” said lead author Amy T. Hutchison, post-doctoral researcher, Adelaide Medical School, University of Adelaide, Australia, in a statement from her university.
“Other women in the study,” she noted, “who either fasted intermittently without reducing their food intake, who reduced their food intake but did not fast, or did not restrict their diet at all, were not as successful in losing weight.”
The new findings from the Effects of Periodic Fasting Versus Daily Energy Restriction on Metabolic Health (PREFER) study were published in the January issue of Obesity.
In this cohort of close to 90 middle-aged and older overweight or obese women who were randomized to the four different strategies, the most successful participants lost about 0.5 to 1 kg per week.
“This study is adding to evidence that intermittent fasting, at least in the short term, may provide better outcomes than daily continuous diet restriction for health and potentially for weight loss,” said senior author Leonie Heilbronn, PhD, associate professor, University of Adelaide and South Australian Health and Medical Record Institute.
Invited to comment, Dorothy D. Sears, PhD, associate professor of medicine, University of California, San Diego, who coauthored a review article about the metabolic effects of intermittent fasting, told Medscape Medical News: “This represents another…study of intermittent fasting providing suggestive evidence of benefit.” However, she pointed out that it was “small and underpowered.”
The researchers agree, saying more research is needed and acknowledging that these findings cannot be generalized to a longer intervention or other populations.
“While the study confirms that intermittent fasting is more effective than continuous diet restriction, the underlying signal for limiting people’s appetite, which could hold the key to triggering effective weight loss, requires further research,” Heilbronn noted.
The group plans to investigate the effectiveness of long-term fasting on men and women in further trials.
Intermittent Fasting, Reduced Calories, or Both?
A continuous reduced calorie diet remains “the cornerstone lifestyle intervention to reduce the risk of developing type 2 diabetes and cardiovascular disease” in overweight people, Hutchison and colleagues write in their article.
However, intermittent fasting might be a better strategy, because people find it difficult to stick to a low-calorie eating plan.
EMA Decision on Lung Cancer Med Called ‘Major Cause of Concern’
When, for the first time in decades, a trial last year showed an improvement in survival in patients with stage III inoperable non–small cell lung cancer (NSCLC), the results swiftly led to approval of the immunotherapy that had demonstrated this benefit — durvalumab (Imfinzi, AstraZeneca).
However, unlike regulatory authorities elsewhere in the world, the European Medicines Agency (EMA) decided to restrict use of this drug to patients whose tumors were positive for programmed death ligand 1 (PD-L1).
Now, this decision has been condemned by lung cancer experts as depriving patients of potentially curative treatment.
An editorial criticizing the decision was published online in the Annals of Oncology on January 8.
The authors describe the EMA’s decision as “surprising” and “a major cause for concern among the thoracic oncology community.”
“At a time when the therapeutic options are improving for lung cancer, a lethal disease for the vast majority of the patients, we worry that the present EMA decision could result in a lost therapeutic opportunity in the curative setting for a sizeable subset of patients,” they write.
Solange Peters, MD, PhD, the lead author of the editorial, is head of medical oncology and chair of thoracic malignancies in the Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. Her coauthors include 21 experts in lung cancer from across Europe, as well as experts from Australia and the United States.
Improved Survival Demonstrated
The approval application for this indication was based on the results from the PACIFIC trial, presented recently at the 19th World Conference on Lung Cancer and published simultaneously in the New England Journal of Medicine. Those results show that treatment with durvalumab after chemotherapy was associated with significantly longer overall survival compared with placebo.
As reported at the time by Medscape Medical News, this study demonstrated, for the first time in decades, an improvement in overall survival for patients with locally advanced stage III unresectable NSCLC.
A secondary endpoint analysis of patient-reported outcomes also indicatedthat durvalumab was well tolerated and did not affect quality of life. Some symptoms, such as dysphagia and alopecia, even improved.
These results led to the approval by the US Food and Drug Administration (FDA) in February 2018 of durvalumab as consolidation therapy after chemoradiotherapy in unselected patients with unresectable stage III NSCLC.
Similar approval was granted by regulatory agencies in Canada, Japan, Australia, Switzerland, Malaysia, Singapore, India, and the United Arab Emirates, despite concerns over its cost-effectiveness.
The EMA, however, chose in July 2018 to limit the use of durvalumab to those patients with tumors that had high levels of expression of PD-L1.
Roche dominates 2019’s big patent expirations
Patent expiration is a challenge that all successful drug makers must face eventually, and Roche is set for a particularly hazardous year on this front. Three of the Swiss pharma giant’s cancer blockbusters will be opened up to cut-price competition in the US this year, though the financial impact will not be quite as painful as it could be.
This is because Avastin and Herceptin are biologics, and the speed at which biosimilars will be adopted is very hard to gauge. Even launch dates remain hard to know in this space: copycat versions of Herceptin are set to appear around mid-year under a settlement forged between Mylan and Roche, but legal wrangling over Avastin could well keep rivals off the market until well into 2020.
Instead, it is probably competition to another major Roche product, Rituxan, that will be felt most keenly by the company this year. Key patents covering the blood cancer treatment lapsed at the end of 2018 in the US, and if swift biosimilar uptake in Europe is anything to go by, the entrance of rivals in the US will be painful. Teva and Celltrion received approval for Truxima last year and are expected to launch at some point in the first half of 2019 under the terms of a deal with Roche, though no details have been disclosed.
Rituxan sold $4.4bn in the US last year, almost as much as Avastin and Herceptin combined. So while these two antibodies might technically be 2019 patent losses, in terms of financial impact, the focus this year will be on Rituxan.
| BIGGEST US PATENT EXPIRIES OF 2019 | |||
|---|---|---|---|
| Product | Company | US total lifetime sales ($bn) | 2018 US sales ($bn) |
| Avastin | Roche | 49.4 | 3.0 |
| Herceptin | Roche | 43.1 | 2.5 |
| Invega Sustenna | Johnson & Johnson | 16.3 | 1.5 |
| Orencia | Bristol-Myers Squibb | 12.8 | 1.0 |
| Tarceva | Roche | 7.5 | 0.3 |
| Source: EvaluatePharma. | |||
Amgen is the lead contender for launching an Avastin biosimilar, though court cases are ongoing and hearings are scheduled for later this year and in 2020. Thus a launch this year is not widely expected.
The vagaries of biosimilar development mean that cut-price competition for Bristol-Myers Squibb’s autoimmune therapy Orencia is also unlikely to emerge anytime soon, in the US at least. The only active project was being pursued by Momenta, but the biotech’s exit from biosimilars left work in limbo.
One US biosimilar market to watch this year will be Neulasta; although patents expired some years ago regulatory hold-ups have delayed launch until the end of 2018. Mylan and others are hoping to crack this blockbuster market in earnest this year.
Elsewhere
The other key Roche product to fall this year is Tarceva, an EGFR kinase inhibitor, which is already a shadow of its former self thanks to newer and better lung cancer drugs. Sales have been in decline for the last four years, which might actually lessen the competitive threat as the product is presumably losing its appeal for generic firms.
And finally J&J will see exclusivity lapse for its hugely successful sustained release anti-psychotic, Invega Sustenna. The product is injected once a month, though a new version administered once every three months, Invega Trinza, was launched more recently in 2015, which will protect sales of the franchise somewhat.
However the world of biologics will be where the big fights are this year, between originators and challengers. With many expecting the biosimilar environment in the US to gradually start improving, demand for the new versions of Rituxan, Herceptin and Neulasta will be tracked with interest.
Blood Test May Predict Alzheimer’s Progression
A blood test predicted disease progression and brain neurodegeneration at very early stages of familial Alzheimer’s disease, researchers reported.
Serum neurofilament light chain (NfL) levels correlated with NfL levels in the cerebrospinal fluid (CSF) and were elevated at pre-symptomatic stages of familial Alzheimer’s disease, according to Mathias Jucker, PhD, of the German Center for Neurodegenerative Diseases in Tübingen, Germany, and colleagues.
Up to 16 years before the calculated onset of dementia symptoms, there were noticeable changes in blood, they reported in Nature Medicine.
The rate of change of serum NfL was key: “It is not the absolute neurofilament concentration but its temporal evolution which is meaningful and allows predictions about the future progression of the disease,” Jucker said in a statement.
These findings add to a growing body of evidencesuggesting NfL might be used clinically as a blood biomarker for Alzheimer’s and other neurodegenerative diseases.
“This is something that would be easy to incorporate into a screening test in a neurology clinic,” co-author Brian Gordon, PhD, of Washington University in St. Louis, said in a statement. “We validated it in people with Alzheimer’s disease because we know their brains undergo lots of neurodegeneration, but this marker isn’t specific for Alzheimer’s. High levels could be a sign of many different neurological diseases and injuries.”
When brain neurons are damaged or dying, they release the NfL protein, which leaks into CSF and blood. Rising levels of NfL in CSF signal neuron loss in stroke, traumatic brain injury, Alzheimer’s, multiple sclerosis, and other neurodegenerative conditions.
This study assessed 405 people from the Dominantly Inherited Alzheimer’s Network (DIAN), a consortium led by Washington University. Participants in DIAN carry one of the gene mutations (APP, PSEN1, PSEN2)known to cause dominantly inherited Alzheimer’s disease. The cohort offers a unique opportunity for researchers to develop accurate predictions about whether and when a family member will develop dementia: a parent with one of these mutations has a 50% chance of passing the genetic error to a child, and a child who inherits a variant is all but guaranteed to develop symptoms of dementia around the same age as the parent.
The researchers examined 243 DIAN participants who carried an early-onset genetic variant and 162 unaffected relatives as controls. DIAN participants were evaluated at baseline and at subsequent follow-up visits (annually to every third year) with blood and CSF tests, imaging, and cognitive tests.
NfL levels in CSF (n=187) and serum (n=405) correlated with one another and were elevated before dementia symptoms occurred. Longitudinal, within-person analysis of serum NfL (n=196) confirmed this elevation, and showed that the rate of change of serum NfL could discriminate mutation carriers from non-mutation carriers almost a decade earlier than cross-sectional absolute NfL levels — 16.2 versus 6.8 years before the estimated symptom onset.
The serum NfL rate of change peaked in participants converting from the pre-symptomatic to the symptomatic stage of Alzheimer’s and was associated with cortical thinning on MRI. Serum NfL also predicted cognitive changes assessed by the Mini–Mental State Examination and Logical Memory test over a 2-year period.
“These results suggest that in the context of Alzheimer’s disease pathology — currently measured by CSF amyloid or amyloid PET, but potentially in the future by blood amyloid — serum NfL could prognosticate the rate of disease progression and potentially be utilized in clinical trials as a surrogate endpoint,” observed Michelle Mielke, PhD, of the Mayo Clinic in Rochester, Minnesota, who was not involved in the research.
“The authors correctly point out that additional studies are needed over the clinical and pathological course of sporadic Alzheimer’s patients, especially because sporadic Alzheimer’s patients are older and are more likely to have co-existent vascular and other brain pathology which can also impact serum NfL levels,” Mielke told MedPage Today.
“Regardless, the current findings are promising and elegantly highlight the potential clinical use of this blood-based marker,” she said.
Future analyses are needed to more accurately pinpoint when serum NfL rate of change is a better predictor of neurodegeneration and cognitive decline than absolute NfL, Jucker noted. And because neurofilaments also accumulate in the blood during the course of other neurodegenerative disorders, this test is only conditionally suitable for diagnosing Alzheimer’s. “However, the test accurately shows the course of the disease and is therefore a powerful instrument for investigating novel Alzheimer’s therapies in clinical trials,” he said.
Data collection and sharing for this project was supported by DIAN (funded by the National Institute on Aging) and the German Center for Neurodegenerative Diseases. Additional support came from the National Institutes of Health, the National Science Foundation, the Swiss National Science Foundation, the National Institute for Health Research University College London Hospitals Biomedical Research Centre, and the MRC Dementias Platform U.K.
Researchers reported relationships with Cognition Therapeutics, Biogen, GlaxoSmithKline, Illumina, Eisai, AbbVie, Pfizer, Denali Therapeutics, Genentech, Roche Diagnostics, Araclon/Grifols, and DiamiR.
Primary Source
Nature Medicine
CMS Announces New Part D Model, Updates Medicare Advantage
The Centers for Medicare & Medicaid Services (CMS) is banking on a new Medicare payment model to help tamp down Part D drug costs by compelling plans to work harder to manage spending in the catastrophic phase of the benefit.
In addition to announcing the launch of this new Part D model, the agency also shared changes to an existing Medicare Advantage model — the Value-Based Insurance Design Model — during a press call Friday morning.
Also, on Thursday the Department Of Health and Human Services (HHS) announced a draft rule governing the “benefit and payment parameters” for issuers on the Affordable Care Act’s exchanges for 2020.
New Part D Model
Under the current structure of Medicare Part D, once patients spend enough on prescription drugs to hit the catastrophic phase of the plan, Medicare is responsible for 80% of coverage, with the remaining 20% is split between patients, who pay 5%, and plans, that cover 15% of costs, explained CMS Administrator Seema Verma on the call. Before that point — at least until patients hit the so-called “donut hole” — plans are responsible for 75% of drug costs once patients satisfy their initial deductible.
This structure inherently rewards insurers for pushing patients toward this catastrophic phase of the benefit, where they have less responsibility, and gives them less of a reason to manage costs for the highest-spending patients, Verma added.
Due to these “perverse incentives,” federal spending in the Part D catastrophic phase grew from $9.4 billion to $37.4 billion — a roughly 17% annual increase — from 2008 to 2017, Verma said.
Moreover, in 2016, the 3.2 million beneficiaries who spent enough on prescription drugs to reach the catastrophic phase and who didn’t qualify for low-income subsidies, spent on average, $3,000 annually in out-of-pocket costs.
Under a new Medicare Part D model, “[f]or the first time, plans will have an incentive to lower costs and negotiate down list prices, and therefore, out-of-pocket expenses for patients who need relief the most,” Verma said.
Plans that enroll in the 5-year voluntary model, beginning in 2020, will take on risk for spending in the coverage gap. They will be given a target level of spending for the catastrophic phase and will share in the savings if they fall below that target, but if they exceed the target, they will “take losses,” she said.
The model will also provide Part D plans with a “rewards and incentives program” to help rein in drug costs and to encourage enrollees to choose drugs with lower list prices.
“CMS is maintaining all current Part D bid, payment, and reconciliation processes, including the application of risk corridors,” an agency fact sheet noted, and “[p]lans will continue to bid a prospective federal reinsurance amount, which will be fully reconciled as per current law.”
Value-Based Insurance Design Model
On Friday, Verma also announced updates to Medicare Advantage’s Value-Based Insurance Design (VBID) Model, which allows plans to reduce cost-sharing for drugs and procedures deemed to be of high value, as a way to lower costs and improve quality of care. The updates allow plans to suggest new higher-value incentives, noted a separate agency fact sheet.
The goal is to enhance health outcomes, prevent injuries, and encourage “the efficient use of health care resources,” noted the sheet.
Medicare Advantage’s VBID model will include three types of benefits/interventions for participating plans:
- Reducing cost-sharing or including new non-healthcare benefits to help manage chronic diseases or other socioeconomic factors. This would apply to beneficiaries who qualify for low-income subsidies or who are “dual eligibles” (enrolled in both Medicare and Medicaid)
- Giving enrolled patients the option to receive telehealth services instead of face-to-face visits, provided the face-to-face option remains available
- Increasing coordination with the aim of improving wellness and increasing the use of advance care planning
Also, starting in 2021, the VBID model will allow Medicare Advantage plans to include Medicare’s hospice benefit — a change which Verma argued will help enhance care coordination between patients, their hospice clinician and other healthcare providers.
Verma stressed that all of the models are voluntary; however, if they demonstrate “a clear threshold for a benefit on quality, cost, and access to benefits,” the models can be scaled up.
Notice of Benefit and Payment Parameters
On Thursday afternoon, HHS released a proposed rule related to the benefit and payment formulas on the Affordable Care Act’s exchanges for 2020.
While HHS stated in a fact sheet that the changes had been kept light to encourage stability and competition, some health policy experts zeroed in on certain changes that may on first glance appear minor but could have significant impact on enrollees’ healthcare costs.
A few of the changes highlighted by the department include:
- Allowing individual market, small-group market, and large-group market health insurers to implement mid-year formulary changes to encourage greater use of lower-cost generic drugs
- Permitting certain insurers to omit the cost-sharing from a patient’s maximum out-of-pocket limit, if a patient chooses a brand drug when a “medically appropriate generic drug” is an option
- Launching an enhanced direct enrollment [DE] pathway, which enables “approved DE partners” to host the marketplace eligibility application on non-exchange websites for plan year 2019
- Basing the premium adjustment percentage (used to set an annual ceiling on cost-sharing, among other things) on estimates from the CMS Office of the Actuary (OACT) instead of using employer-sponsored insurance premiums — used in past years — resulting in a premium increase of about 29.7% over the period from 2013 to 2019
- Using the same premium index, proposing a maximum cost-sharing limit of $8,200 for “self-only coverage” and $16,400 for all other coverage for the 2020 benefit year — an increase of about 3.8% over 2019
The proposal was criticized by the Center on Budget and Policy Priorities (CBPP), a left-leaning think tank here, for the way it changes the ACA’s “applicable percentages” and maximum out-of-pocket limits. “Under the administration’s proposal, both the share of income that people pay in premiums (after tax credits) and the maximum out-of-pocket limit would increase more rapidly than they otherwise would have,” CBPP’s Aviva Aron-Dine, PhD, and Matt Broaddus noted in a report released Friday.
The end result is that 7.9 million people would pay higher premiums due to receiving smaller tax credits. For instance, “a family of four with income of $80,000 would pay an extra $196 in 2020 premiums as a result of the rule,” the authors noted.
In addition, because the cap on out-of-pocket limits would also rise, a family forced to address an expensive illness or injury could be required to pay an additional $400 in medical bills, the authors noted.
Novo Nordisk Fund Backs Therapies Combatting Antimicrobial Resistance
Novo Nordisk’s investment arm, Novo Holdings, invested a little more than $20 million in four different companies over the course of 2018 through its REPAIR Impact Fund. That $165 million fund was established last year to support companies developing therapies to combat antimicrobial resistance.
The World Health Organization regards antimicrobial resistance as one of the greatest health threats to mankind across the globe. It is estimated that more than 700,000 people die each year from infections resistant to most or all antibiotics. That threat is expected to eclipse cancer-related deaths by 2050, Novo Holdings said this morning, as it noted its investments. Novel approaches are urgently needed to tackle the growing tide of antibiotic-resistant infections, the investment firm said.
The fund invested in four companies last year, including Entasis Therapeutics, which has an anti-infective discovery platform and a clinical pipeline of meaningfully differentiated programs targeting serious bacterial infections. The Novo Nordisk REPAIR Fund invested $10 million into the company’s $75 million IPO. Entasis, a spinout of AstraZeneca, emerged in July 2015 with a number of former AstraZeneca anti-infective scientists leading the charge. Last year, Entasis announced positive topline results from its Phase II clinical trial of ETX2514, a beta-lactamase inhibitor, in combination with sulbactam, to treat complicated urinary tract infections (cUTI) including acute pyelonephritis (kidney infection) in adults. Novo Holdings pointed to that company’s preclinical pipeline, which includes a new class of non-β-lactam PBP Inhibitors (NBP) targeting multi-resistant Pseudomonas aeruginosa infections, also supported by the Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X). Also last year, Entasis joined the Antimicrobials Working Group (AWG), which includes 18 antimicrobial drug and diagnostic device development companies. The AWG has a vision of improving the regulatory, investment and commercial environment for emerging infectious disease companies.
The REPAIR fund also invested a little more than $4 million (€3.6 million) into Minervax, a Danish biotech company that was spun out of Lund University. Minervax is developing a prophylactic vaccine against group B Streptococcus (GBS) responsible for 50% of life-threatening infections in newborns, as well as stillbirths and preterm deliveries in pregnant women.
Also, the fund was used to provide an infusion of $1.5 million (€1.5 million) into U.K.-based Procarta Biosystems. Procarta is developing a pipeline of antibacterials from its oligonucleotide antimicrobial platform. The platform has a novel nanoparticle approach targeting a new class of antibiotics targets, transcription factors. Procarta’s lead asset is PRO-202, a preclinical therapeutic aimed at treating complicated urinary tract infections and complicated intra-abdominal infections.
The fourth company boosted by Novo Holdings’ REPAIR fund was Polyphor. That company is developing novel outer membrane protein-targeting antibiotics addressing the World Health Organization’s five deadliest and most resistant Gram-negative bacterial pathogens. The REPAIR fund has already invested $6.8 million and plans to invest another $4.4 million if the company hits certain milestones with its programs.
In addition to announcing its investments for last year, Novo Holdings, tapped Dr. John H. Rex, a noted leader in the field of infectious disease therapy, as the chairman of its Scientific Selection Board.
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