Mesoblast Phase 3 Trial of Heart Failure Cell Therapy Completes Recruitment

Mesoblast Limited (ASX:MSB; Nasdaq:MESO), world leader in development and commercialization of allogeneic (off-the-shelf) cellular medicines, today announced that it has completed patient recruitment in the events-driven Phase 3 trial of its product candidate Revascor (MPC-150-IM) for advanced chronic heart failure.

Mesoblast Chief Executive Dr Silviu Itescu stated: “Completion of recruitment in this Phase 3 trial, the largest cell therapy trial for heart failure, is a key milestone for Mesoblast and has been achieved on plan. This is a substantial step forward in our objective to bring an effective therapy to countless patients with progressive heart failure, and a tremendous commercial opportunity for Mesoblast.”

The Phase 3 trial is evaluating whether Revascor reduces recurrent non-fatal heart failure-related major adverse cardiac events (HF-MACE), and prevents or delays terminal cardiac events (TCEs), defined as cardiovascular death, heart transplant or placement of an artificial device, over at least 12 months. In a previous Phase 2 trial, a single dose of Revascor prevented any TCEs or hospitalization events over three years in a similar patient cohort.

The Phase 3 trial has enrolled approximately 570 patients across 55 centers in North America. This enrollment target was guided by the observed reduction in event rate in the Phase 2 trial and reinforced by the successful outcome of a pre-specified futility analysis of the Phase 3 trial’s primary endpoint performed after the first 270 patients were enrolled.

The trial’s co-principal investigator, Dr Emerson Perin, Medical Director of Texas Heart Institute and Director of its Stem Cell Center, said: “We are very pleased to have completed recruitment in this important trial of a cellular therapy for advanced heart failure patients who have few alternatives. If the Phase 3 trial results confirm the earlier Phase 2 data, where we saw improvements in patient function as well as reductions in hospitalizations and deaths, this important technology will transform cardiovascular care and would provide a powerful new treatment for advanced heart failure.”

There are over 8 million patients with heart failure in the United States alone, with 15-20% refractory to all existing medicines and progressing to advanced heart failure1(New York Heart Association Class III or IV). These patients represent a major unmet medical need due to their high rates of HF-MACE events and mortality.

Dr Itescu added: “Over the past 12 months, Mesoblast has completed recruitment in all three of its Phase 3 trials, for acute graft versus host disease, chronic low back pain, and now chronic heart failure.”

https://www.marketscreener.com/MESOBLAST-LIMITED-6499027/news/Mesoblast-P3-Trial-of-MSB-s-Cell-Therapy-in-CHF-Completes-Recruitment-27829642/

Adverum Biotechnologies Provides 2019 Outlook

Adverum Biotechnologies, Inc. (Nasdaq: ADVM), a clinical-stage gene therapy company targeting unmet medical needs in ophthalmology and rare diseases, today reviewed recent progress and provided an outlook for 2019.

“For our lead gene therapy ADVM-022 for the treatment of wet AMD, we are building off of last year’s momentum to execute our ongoing OPTIC phase 1 clinical trial,” said Leone Patterson, chief executive officer of Adverum Biotechnologies. “In a very short period, we have dosed our first patient in the OPTIC phase 1 trial, published long-term preclinical efficacy data in a leading scientific journal, and received Fast Track designation for ADVM-022. With this key groundwork complete, this year our primary focus is on advancing this gene therapy for an initial indication in wet AMD and evaluating additional anti-VEGF indications to pursue. We have sufficient cash to fund operations at least through the first half of 2020, including interim data from the three cohorts in the OPTIC trial. Our team is excited to be working on developing this novel single intravitreal injection therapy for patients.”

Key Accomplishments for 2018

	•	In December 2018, long-term preclinical expression and efficacy data on ADVM-022 in wet age-related macular degeneration (wet AMD) were published in Molecular Therapy, a leading peer-reviewed scientific journal. The data in this publication combined with two year preclinical expression data presented in October 2018 at the European Society of Gene and Cell Therapy (ESGCT) showed the following:
		A single intravitreal injection of ADVM-022 in non-human primates (NHPs) at dose ranges of 2 x 10 11 vg/eye to 2 x 10 12 vg/eye provided stable intraocular expression of aflibercept at levels comparable with the levels measured in aflibercept recombinant protein-injected eyes approximately 3 to 4 weeks post-dose in all of the following: vitreous humor, aqueous humor, retina and choroid A single intravitreal injection of ADVM-022 provided robust and durable expression of aflibercept, sustained for approximately two years post-dose in NHPs In a laser-induced choroidal neovascularization model in NHPs, a single intravitreal injection of ADVM-022 13 months before lasering prevented the occurrence of clinically relevant choroidal neovascularization lesions, similar to animals that received a bolus of intravitreal aflibercept (standard-of-care) at the time of lesioning A single intravitreal injection of ADVM-022 delivering a continuous supply of aflibercept may provide an effective long-term treatment option and prevent further vision loss for patients with wet AMD The full online publication can be accessed at the following link: https://doi.org/10.1016/j.ymthe.2018.11.003.
	•	In November 2018, Adverum dosed the first patient in the OPTIC phase 1 trial evaluating a single intravitreal injection of ADVM-022 for patients with wet AMD. ADVM-022 (AAV.7m8-aflibercept) is designed to provide long-lasting therapy without the need of chronic or frequent anti-VEGF injections
	•	In September 2018, Adverum received Fast Track designation for ADVM-022 in wet AMD from the U.S. Food and Drug Administration (FDA). Fast Track is a process designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need. Despite the availability of anti-VEGF therapies, patients with wet AMD still have a significant burden from the frequency of injections and undertreatment may lead to vision loss
	•	In late August 2018, Adverum announced that the IND application for ADVM-022 in patients went active

2019 Outlook – Planned Pipeline MilestonesADVM-022 for wet AMD

• Provide an update on enrollment from the OPTIC phase 1 clinical trial in the first half of 2019
• Provide interim data on the three cohorts from the OPTIC phase 1 clinical trial by the first quarter of 2020

Rare Disease Program

• Provide an update on rare disease program’s preclinical development plan in the first half of 2019

Financial Guidance
Adverum’s cash, cash equivalents and marketable securities were $217.9 million as of September 30, 2018. Adverum expects this quarter-end cash position to fund operations at least through the first half of 2020.

Upcoming Events

	•	Adverum plans to participate in the following upcoming conferences:
		J.P. Morgan’s 37th Annual Healthcare Conference in San Francisco January 7-10, 2019. CEO Leone Patterson will present on Thursday, January 10 at 8:00 am PT Leerink’s 8th Annual Global Healthcare Conference in New York, February 27-March 1, 2019 Cowen’s 39th Annual Health Care Conference in Boston, March 11-13, 2019

https://www.marketscreener.com/ADVERUM-BIOTECHNOLOGIES-I-27535811/news/Adverum-Biotechnologies-Provides-2019-Outlook-27829690/

Xenon Pharmaceuticals Outlines 2019 Key Milestones

Xenon Pharmaceuticals Inc. (Nasdaq:XENE), a clinical stage biopharmaceutical company, today provided a corporate update and outlined its anticipated key milestone events in 2019.

Dr. Simon Pimstone, Xenon’s Chief Executive Officer, said, “Xenon is entering 2019 in a strong position, poised to support multiple neurology programs that are expected to be in Phase 2 or later stage development this year. With four distinct therapeutic candidates – XEN496, XEN1101, XEN901 and XEN007 – that are aimed at treating neurological disorders, including epilepsy, we intend to pursue a variety of development strategies, such as those focused on using a ‘precision medicine’ approach to address rare pediatric disorders including KCNQ2 epilepsy as well as those targeting broader patient populations, including adult patients with focal epilepsy. During 2019, we expect to advance our ongoing XEN1101 Phase 2b clinical trial in adult focal epilepsy, initiate a Phase 3 clinical trial for XEN496 for the treatment of KCNQ2 epilepsy, and initiate a Phase 2 clinical trial for XEN901 in either a pediatric or adult epilepsy indication based on regulatory feedback. In addition, we expect to initiate at least one Phase 2 clinical trial for XEN007 in an orphan neurological indication and continue our drug discovery efforts to identify new therapeutic candidates.”

Anticipated Milestones

• XEN496 (active ingredient ezogabine) is a Kv7 potassium channel modulator being developed for the treatment of KCNQ2 epileptic encephalopathy (KCNQ2-EE). Ezogabine was previously approved by the U.S. Food and Drug Administration (FDA), as an anti-epileptic drug (AED) as an adjunctive treatment for adults with focal seizures with or without secondary generalization. Xenon received orphan drug designation (ODD) from the FDA for XEN496 as a treatment of KCNQ2-EE. A steering committee made up of key opinion leaders in the KCNQ2-EE and pediatric epilepsy fields has been established to help guide the clinical development of XEN496. In response to Xenon’s pre-IND briefing package submission, the FDA indicated that it was acceptable to study XEN496 in infants and children up to 4 years old, and that a single pivotal trial in approximately 20 patients may be considered adequate in order to demonstrate XEN496’s efficacy in KCNQ2-EE. Xenon is currently finalizing a pediatric-specific formulation to complete pre-clinical formulation testing with a final drug product expected in the second quarter of 2019. Xenon expects to file an Investigational New Drug (IND) application in the third quarter of 2019, and, based on regulatory feedback, Xenon expects to initiate a Phase 3 clinical trial thereafter.
• XEN1101 is a Kv7 potassium channel modulator being developed for the treatment of epilepsy and potentially other neurological disorders. Xenon announced final data from its XEN1101 Phase 1 clinical trial and the related transcranial magnetic stimulation (TMS) studies at the American Epilepsy Society (AES) Annual Meeting in December 2018. Based on the encouraging Phase 1 data and TMS results, Xenon has initiated a Phase 2b clinical trial in adult patients with focal epilepsy. A Clinical Trial Application (CTA) has been accepted by Health Canada enabling the start of patient screening, and the first patient in the XEN1101 Phase 2b clinical trial is expected to be enrolled in the near term. Xenon has also submitted regulatory filings to support the clinical development of XEN1101 in other jurisdictions, including the United States and Europe. The XEN1101 Phase 2 clinical trial is designed as a randomized, double-blind, placebo-controlled, multicenter study to evaluate the clinical efficacy, safety and tolerability of XEN1101 administered as adjunctive treatment in adult patients with focal epilepsy. Approximately 300 patients will be randomized in a blinded manner to one of three active treatment groups or placebo in a 2:1:1:2 fashion (XEN1101 25 mg : 20 mg : 10 mg : Placebo). The primary endpoint is the median percent change in monthly focal seizure frequency from baseline compared to treatment period of active versus placebo. Depending upon the rate of enrollment, top-line results from the XEN1101 Phase 2 clinical trial are anticipated in the second half of 2020.
• XEN901 is a potent, highly selective Nav1.6 sodium channel inhibitor being developed for the treatment of epilepsy. Xenon announced interim results from its XEN901 Phase 1 clinical trial and the related pilot TMS study at the AES Annual Meeting in December 2018. The next steps for XEN901 include completing the Phase 1 clinical trial and continued planning for Phase 2 clinical development evaluating XEN901 as a treatment for adult focal seizures or for rare, pediatric forms of epilepsy, including SCN8A gain-of-function epilepsy patients, depending on feedback from planned discussions with regulatory agencies. Xenon expects to receive regulatory feedback on advancing XEN901 directly into pediatric SCN8A gain-of-function epilepsy patients in the second quarter of 2019, and pediatric formulation development and juvenile toxicology studies are underway.
• XEN007 (active ingredient flunarizine) is a CNS-acting calcium channel inhibitor that directly modulates the Cav2.1 channel. Flunarizine has been used outside of the U.S. in the prevention of chronic migraine, and in case studies, it has been reported to have clinical benefit in other neurological disorders, including hemiplegic migraine (HM) and alternating hemiplegia of childhood (AHC). Xenon has received ODD from the FDA for XEN007 for the treatment of HM and AHC. In addition, Xenon entered into key agreements in order to access regulatory files and manufacturing support to potentially enable an accelerated clinical development of XEN007 directly into a Phase 2 clinical trial. Xenon is currently evaluating various development strategies for XEN007, including the support of at least one Phase 2 clinical trial in an orphan neurological indication.
• As of September 30, 2018, cash and cash equivalents and marketable securities were $127.1 million. Based on current assumptions, which include fully supporting the planned clinical development of XEN496, XEN1101, XEN901 and XEN007, Xenon anticipates having sufficient cash to fund operations into 2021, excluding any revenue generated from existing partnerships or potential new partnering arrangements.

https://www.marketscreener.com/XENON-PHARMACEUTICALS-INC-18411162/news/Xenon-Pharmaceuticals-Outlines-2019-Key-Milestones-27829731/

Ind. group aims to distribute nearly double naloxone doses in 2019

Local supplies of the opioid-overdose reversal drug naloxone increased and became more accessible to the public in 2018.

The Indiana Recovery Alliance reports it distributed more than 26,500 doses of naloxone last year and aspires to dispense 50,000 doses this year.

Of the 30,000 doses the IRA ordered in 2018 from drug-giant Pfizer, preliminary totals indicate the syringe-services program distributed 26,646. Most, but not all, of those doses were handed out in Monroe County, according to IRA director Chris Abert.

The IRA uses two different tracking sheets to count what they distribute, Abert explained.

There’s a daily tracking log for naloxone distributed from the IRA’s office, van and at training sessions. They use another log if the Bloomington harm-reduction program travels out of county for naloxone training sessions. The hand-tabulated logs get transferred to a digital spreadsheet; distribution totals are double-checked through invoices and inventory counts.

Orders for the antidote are placed every few weeks, so the IRA’s supply features several different expiration dates.

“Our goal is 50,000 in 2019, and we have secured the funding from private donations,” Abert said. “It’s helped us build the capacity to provide naloxone.”

Donations of all denominations have contributed to the IRA’s increased naloxone supply. In recent years, $10 donations have been made on the organization’s website, work groups have raised $10,000 gifts and an anonymous benefactor donated $100,000.

“We don’t spend a dime of taxpayer money on this program,” Abert said.

Local government does fund some naloxone distribution, however, through state and federal grants.

The Monroe County Health Department distributes naloxone to organizations, such as law enforcement agencies and Centerstone, that are registered with the Indiana Department of Health as naloxone providers. Partnerships are currently in the works with the Monroe County probation department and the IU Health Bloomington Hospitalemergency room.

Though it’s difficult to keep track of ultimately how much is passed out and used through the original supply at the Monroe County Health Department, administrator Penny Caudill said doses passed out are increasing. A new shipment recently arrived at the health department to replace a shipment of 500 from August. It’s been distributed.

Naloxone training is provided at the health department, 119 W. Seventh St., where anyone can ask to learn how to administer the drug, and take some with them.

“No one is required to take naloxone after they train. Someone could participate and say, ‘I’m not comfortable to do it quite yet,’ or hopefully they say, ‘Yes, I will take some in case I come across someone who might be overdosing,'” Caudill said.

Training is mandatory if naloxone is taken from the health department, and an appointment is required.

For 2019, the IRA has a goal of offering two naloxone training sessions in all 92 counties in the state, and the alliance will focus efforts on vulnerable populations.

“It’s important that we get the naloxone into the hands of the people who do drugs and their families,” he said.

Other organizations have partnered with IRA recently provide naloxone training.

In its first of four opioid-related events, the Greater Bloomington Chamber of Commerceinvited IRA to give training and pass out naloxone. Jim Inman, Chamber director of marketing communications, said about 25 kits were passed out at that event.

The opioid-overdose reversal drug comes in a variety of forms and prices.

Most expensive by far are the Evzio auto injectors, two dose kits complete with recorded audio instructions, by drug-maker Kaleo. FDA-approved in 2014, Kaleo has increased its price from $575 to more than $4,000 a kit.

Last March, Adapt Pharma offered its Narcan nasal spray at a cost of $37.50 a dose for police and fire departments, harm-reduction groups, schools and community centers. The drug maker’s website claimed the public interest price was at a 40 percent discount.

Naloxone the IRA purchases is among the least expensive because it is administered by way of intramuscular injection — tiny medicine vial, needle and syringe.

Abert said he was contractually obligated not to discuss the discounted pricing rates the IRA has worked out with Pfizer, which purchased naloxone manufacturer Hospira in 2015.

“When I do a price comparison about how much naloxone we can get out there, compared to the state and other organizations, it’s astounding,” he said.

The IRA started its syringe services program on Valentine’s Day 2016 after the Monroe County Health Department deemed increased rates of hepatitis C infections and heroin overdoses a public health emergency in August 2015. Long before that, volunteers with the harm-reduction program offered naloxone, sterile medical supplies and personal hygiene products.

The IRA’s naloxone inventory on Thursday consisted of about 3,000 intramuscular injection doses, 150 auto injector kits and a small supply of the nose spray.

https://www.marketscreener.com/PFIZER-23365019/news/Pfizer-IRA-aims-to-distribute-nearly-double-the-naloxone-doses-in-2019-27829701/

DaVita started by Deutsche Bank

Deutsche Bank initiated coverage on shares of Davita (NYSE:DVA) in a report released on Thursday morning, MarketBeat Ratings reports. The firm issued a buy rating and a $60.00 target price

http://bharatapress.com/2019/01/06/davita-dva-coverage-initiated-by-analysts-at-deutsche-bank/

Physical therapy also can help prevent sports injuries

Physical therapy helps people recover from sports injuries, but it also can help prevent them.

This approach, called proactive physical therapy, can help correct imbalances in amateur and professional athletes that can increase the risk of injury, according to Dean Plafcan, a physical therapist with Penn State Health.

“Consider enlisting a physical therapist or athletic trainer to look for weaknesses or imbalances in one part of the body that might be impacting other areas,” Plafcan said in a university news release.

“The result of identifying problem areas and doing targeted therapy and training can be better athletic performance with less risk of pain and injury,” he added.

Plafcan noted that many amateur golfers complain about back pain, and the likely reason is their desk job. Spending a lot of time sitting leads to shortened hip flexors, the muscles on the front of the hip. This forces the lower back to do more of the work during a golf swing, resulting in pain.

“Proactive physical therapy can diagnose this imbalance and improve hip mobility,” Plafcan said. “The result is less risk of back pain, plus a more powerful downswing and greater yardage on the golf course.”

He also said that one-sided body use in many sports leads to physical imbalance.

“A baseball player, tennis player or golfer constantly works one side of the body more than the other, depending on whether the athlete is right-handed or left-handed,” Plafcan said.

“Yes, these athletes need great strength on their dominant sides to excel in their sport, but weakness on the other side of the body can lead to overcompensation and injury,” he explained. “By targeting exercise to increase symmetry in strength and flexibility, the athlete can improve overall performance.”

More information

The American Academy of Orthopaedic Surgeons offers sports injury prevention tips.

SOURCE: Penn State Health, news release, November 2018

https://consumer.healthday.com/physical-therapy-information-28/physical-therapy-news-532/physical-therapy-can-keep-sports-injuries-at-bay-739429.html

NanoString Sees FY18 Revenue $83.5M, Exceeding High End of Guidanc

NanoString Technologies, Inc. (NASDAQ:NSTG), a provider of life science tools for translational research and molecular diagnostic products, today provided preliminary operational and financial results for the fourth quarter and fiscal year ended December 31, 2018.

“With 16% growth in our product and service revenue, 2018 was a year of renewed commercial momentum and strong execution as the investments we’ve made in our people and commercial processes began to pay off,” said NanoString president and chief executive officer, Brad Gray. “Customer demand for our GeoMx Digital Spatial Profiler (DSP) is exceeding internal expectations, resulting in a strong pipeline of pre-orders ahead of the planned launch. 2019 promises to be an exciting year, with the GeoMx DSP launch expected to accelerate our top-line growth in the second half of the year.”

Financial Highlights:

For the fourth quarter of 2018, product and service revenue is expected to be approximately $23.5 million, exceeding the upper end of the company’s guidance range of $22 to $23 million.

Product and service revenue for fiscal year 2018 is expected to be approximately $83.5 million, exceeding the upper end of the company’s guidance range of $82 to $83 million.

Total revenue for the fourth quarter of 2018 is expected to be approximately $30 million, including approximately $6 million of collaboration revenue, versus prior guidance of $28 to $29 million. Total revenue for fiscal year 2018 is expected to be in the range of $106 to $107 million, including approximately $23 million of collaboration revenue, versus prior guidance of $104 to $106 million.

Cash, cash equivalents and short-term investments totaled more than $90 million as of December 31, 2018.

Operational Highlights:

• Approximately 135 nCounter® Analysis Systems were sold in 2018.
• Installed base of approximately 730 nCounter Analysis Systems at December 31, 2018, an increase of approximately 20% since year-end 2017.
• Shipped first beta GeoMx Digital Spatial Profilers during the fourth quarter.
• Announced that the GeoMx Priority Site program was over-subscribed, yielding pre-orders for more than 30 instruments.

Brad Gray will give a corporate update at the JP Morgan Healthcare conference at 3:30 p.m. PST on Wednesday January 9th, 2019. A live webcast of the presentation will be available online from the investor relations page of the company’s corporate website at www.nanostring.com. After the live webcast, the presentation will remain available on the website for approximately 30 days.

These preliminary results are based on management’s initial analysis of operations for the quarter and year ended December 31, 2018 and are subject to further internal review and audit by the company’s external auditors.

https://www.nasdaq.com/press-release/nanostring-technologies-provides-preliminary-operational-and-financial-results-for-fourth-quarter-20190106-00049