Merck Ebola Vaccination Begins in Democratic Republic of Congo

Health officials in the Democratic Republic of Congo began administering an experimental Ebola vaccine on Monday, as the country battles to contain its ninth outbreak of the hemorrhagic fever.

The first people to receive the vaccine were staff at a 20-bed Ebola treatment center set up by medical charity Doctors Without Borders in the northwestern city of Mbandaka, said Jessica Ilungu, a spokeswoman for Congo’s public-health ministry. People, including relatives, who have come into contact with patients suspected of having contracted the virus would be next, she added.

“Our target is to reach as many contacts as we can before the end of the week,” Ms. Ilunga said.

An initial shipment of 4,000 doses of the experimental vaccine, developed by Merck & Co., arrived in the inland port city of 1.2 million people on the Congo River on Saturday.

The vaccine is being administered for the first time since it showed promising results two years ago in Guinea, in the final stages of an Ebola epidemic that killed more than 11,300 people across West Africa. If it proves effective in Congo, the vaccine could permanently alter how the world responds to the virus, which is passed on through bodily fluids such as saliva or blood.

At least 30 health workers with experience in administering the vaccine traveled from Guinea to Mbandaka over the weekend. Teams from the World Health Organization, Doctors Without Borders and the International Rescue Committee were also in Mbandaka helping with the vaccination campaign.

The WHO is sending an additional 7,540 doses to Congo, but getting the vaccine to those at highest risk of contracting the virus has been complicated by the need to keep it at below-freezing temperatures in a tropical country with one of the most unreliable electricity grids in the world.

The public-health ministry on Sunday said it had confirmed four cases of Ebola in Mbandaka, one of them fatal, plus two further suspected cases.

The spread of the disease from the remote region of Bikoro to Mbandaka has raised concerns that it could move downstream to the capital Kinshasa and then across the river to Brazzaville, the capital of the neighboring Republic of Congo. The WHO on Friday said there was a “very high” risk to public health in Congo, but stopped short of declaring the outbreak a global health emergency, saying it could be contained.

The number of Ebola cases in Congo as a whole has risen to 49, including 27 deaths, Congo’s public-health ministry said Monday. The latest victims include a nurse who died in Bikoro, a remote town near the epicenter of the current outbreak along the northwestern border with the Republic of Congo.

Seth Berkley, chief executive of GAVI, the international vaccine alliance, said clinical trials have shown the Ebola vaccine to be safe and effective.

“This is an important step for a vaccine with huge potential,” he said.

The WHO said it had identified more than 600 people in Mbandaka and Bikoro who had come in contact with patients confirmed or suspected of having Ebola and would soon be vaccinated in an effort to ringfence the virus.

In Mbandaka, officials and health workers rushed to keep the virus from spreading. At the airport, passengers underwent obligatory temperature screenings, while Congo’s public-health ministry ran radio adverts telling people in Mbandaka to not shake hands, relief officials said. Schools were distributing fliers warning students against close body contact such as kissing.

“The longer we wait to mobilize a response, the more people will become infected and the more difficult it will become to contain this outbreak, ” said Michelle Gayer, director of emergency health at International Rescue Committee. “As we all can remember — the lives of millions are at stake”

The WHO said it was seeking $26 million to fund its response in Congo. Congo’s government over the weekend approved $4 million to facilitate emergency operations, while the U.S. provided $1 million to WHO to help combat the disease.

https://bit.ly/2KHNVLy

Dova med for chronic liver disease OKd by FDA

FDA approves Doptelet for chronic liver disease patients undergoing procedures

https://bit.ly/2kgX9TL

Nicotine linked with obesity-fighting ‘beige’ fat

Scientists engaged in the fight against obesity have long been aware that white fat cells are unhealthy because they store triglycerides and other harmful substances, while brown fat is desirable because it burns energy and protects against excessive weight gain. But efforts to understand how white fat becomes “beige” and takes on all the good characteristics of brown fat—and to translate that into antiobesity treatments—have largely failed.

Now researchers from the University of Michigan and American University believe they’ve uncovered a signaling pathway that prompts beige cells to burn energy. Surprisingly, they discovered that nicotine contributes to this process—a revelation that could explain why some smokers say the habit helps them lose weight.

The team zeroed in on a signaling pathway called CHRNA2. By monitoring the activity of more than 20 neurotransmitters in mice, they discovered that the pathway is active when the body is converting brown fat to energy to protect against cold—one of the key functions of this type of adipose tissue. When the researchers deactivated CHRNA2, the mice not only struggled to fend off the chills, they also gained weight, according to a statement.

When the researchers started measuring levels of the neurotransmitters in fat cells, they discovered that nicotinic acetylcholine was inducing CHRNA2 signaling. They believe therapies targeting the CHRNA2 signaling pathway could be effective in fighting obesity. Their research was published in the journal Nature Medicine.

“Until recently, we thought this pathway primarily existed in brain cells, the neuromuscular junction, and affected neuronal signaling, and we didn’t know it was prevalent in certain fat cells,” said co-author Alexander Zestos, a bioanalytical neurochemist at American University, in the statement. “It raises all sorts of new questions. Is it the density of the receptors that a person has, or is it the way the receptors are activated, that contributes to one’s ability to gain or lose weight? What is the connection between smoking and weight loss or weight gain?”

The researchers also investigated mice engineered to lack the CHRNA2 protein, and discovered that when they were fed a high-fat diet, they had more weight gain and higher levels of insulin and blood glucose. Those are signals of diabetes risk, said researchers at the University of Michigan in a statement.

The potential to turn white fat beige has inspired other obesity researchers, too. A team at the Perelman School of Medicine at the University of Pennsylvania has been investigating a different signaling pathway that involves the proteins FLCN and mTOR, which they discovered work in tandem to prevent the browning of white fat. When they deleted the gene that makes FLCN in mice, they were able to prompt the beiging of white fat. They had previously achieved the same result in mice when they activated mTORC1 and mTORC2.

The nicotine connection is intriguing to Zestos and his co-authors, and they are currently searching for a compound that can target CHRNA2 signaling for weight loss and to prevent obesity, sans cigarettes, of course. They are also investigating other neurological chemicals that may activate beige fat.

https://bit.ly/2IzBMaZ

XTant Medical gets clearance for spinal implant system

Xtant Medical Holdings, Inc. (NYSE American: XTNT), a leader in the development of regenerative medicine products and medical devices, announces U.S. Food and Drug Administration (FDA) 510(k) clearance for InTice™-C Porous Titanium Cervical Interbody System.

InTice-C is designed using OsteoSync Ti, a best-in-class, cost-effective, highly porous titanium scaffold material for improved implant fixation. The material more closely resembles the bioscaffold of cancellous bone, and further combines Xtant Medical’s hardware and biologic portfolios. In addition to InTice-C serving as a bioactive scaffold, it is also cleared for use with Xtant’s proprietary allograft lines, including OsteoSponge®, 3Demin® Cortical Fibers, and OsteoVive™ viable cell allograft.

“InTice-C represents Xtant’s latest addition to our spinal implant portfolio and is our first spinal implant to be engineered using a best-in-class porous titanium material,” stated Dr. Gregory Juda, Chief Scientific Officer and General Manager of Xtant Medical. “The porous architecture of the titanium was designed to improve implant fixation, both prior and post fusion. We expect a positive reception of this technology from our surgeon customers in the cervical spine market.”

The InTice-C Is designed to provide cervical intervertebral body fusion options for each patient’s varied anatomy. It is offered in multiple footprint, height and endplate options. The commercial pure titanium structure offers continuous pore interconnectivity from the top to the bottom as well as from the outer perimeter to the large central graft cavity of the implant. This optimizes vascularization to the fusion site allowing the implant to be a participant in the fusion process. The implant utilizes machined endplate structures in conjunction with the inherent texture of the porous titanium to provide migration resistance. The implant is offered in individual sterile packages. InTice-C was developed in collaboration with Sites Medical.

InTice-C will help the Company further penetrate the $285 million dollar cervical spine market. Xtant’s other cervical interbody options include Calix®-C, Calix-C PC, Atrix-C®, and Irix®-C, which offer PEEK, PEEK with a plasma-coated titanium, a structural biologic solution, and a standalone cervical option, respectively.

https://yhoo.it/2kemSwo

Avenue Therapeutics’ IV Tramadol Shows Stellar Data in Phase 3

Avenue Therapeutics, headquartered in New York City, announced its Phase III clinical trial of IV tramadol hit its primary endpoint of statistically significant improvement in Sum of Pain Intensity Difference over 48 hours (SPID48) in patients with moderate to moderately severe postoperative pain after bunionectomy surgery.

The trial compared the IV tramadol to a placebo, evaluating SPID48. The trial also met key secondary endpoints and showed a clear dose response. The company plans to initiate another Phase III trial of IV tramadol in patients after abdominoplasty surgery in this year’s third quarter.

Patients were randomized one-to-one-to-one (1:1:1) on a postoperative regimen of 50 mg of IV tramadol, 25 mg of IV tramadol or placebo administered over 15 minutes at hours 0, 2, 4 and once every 4 hours after that, up to 13 doses. The key secondary endpoints included SPID24, total consumption of rescue medicine and Patient Global Assessment.

“There is a clear need for new therapies in the postoperative pain setting, where patients are often treated with Schedule II narcotics due to a lack of other options,” said Harold Minkowitz,an investigator in the Phase III program, in a statement. “IV tramadol, which acts by a dual mechanism, is widely used outside the U.S. in the postoperative setting. These Phase III results demonstrate that IV tramadol is well tolerated and rapidly and effectively induces pain relief in patients following bunionectomy surgery, a generally painful procedure, and suggest that IV tramadol could be an important new therapy for managing postoperative pain in our patients.”

The company’s hope is that IV tramadol might be a bridge to the widely used oral tramadol, and that the combination of IV tramadol leading to oral tramadol might replace Schedule II narcotics.

If the Phase III trial in abdominoplasty surgery is successful, Avenue hopes to file a New Drug Application (NDA) with the U.S.Food and Drug Administration (FDA) in late 2019.

At Avenue’s first-quarter financial report on May 3, it reported cash, cash equivalent and short-term investments of $15 million. Research-and-development expenses for the three months ended March 31, 2018, were $9.4 million. G&A expenses for the quarter were $1 million. The net loss for the quarter was $10.4 million, or $1.03 per share.

“Coupled with recent additions to our patent portfolio, which was strengthened by the receipt of Notices of Allowance for three patent applications in the first quarter,” said Lucy Lu, the company’s president and chief executive officer, in a statement, “we are making progress toward our goal of introducing IV tramadol as a treatment option for use in the management of postoperative pain. Patients and physicians have an increasingly pressing need for medicines that can provide rapid and sustained relief without also introducing the risk of opioid dependence, and we are working hard to advance IV tramadol to address this gap in the acute pain space.”

In the trial, IV tramadol was well-tolerated with no indications of drug-related serious side effects. One patient in the 50 mg arm discontinued due to vomiting. The most common side effects in the 50 mg arm were nausea, vomiting, dizziness and somnolence. Usually, these were mild or moderate, with only 3 percent of patients experiencing vomiting, a Grade 3 event. There were no Grade 4 events in the tramadol 50 mg group.

https://bit.ly/2Ljbyvl

Genentech Med Significantly Cuts Bleeding in Late-Stage Hemophilia Study

Genentech’s hemophilia treatment Hemlibra continues to demonstrate its efficacy in treating patients. New late-stage data presented at World Federation of Hemophilia 2018 World Congress shows the drug significantly reduced treated bleeds in a broad patient population in two separate studies.

In the HAVEN 3 study people with hemophilia A without factor VIII inhibitors who received Hemlibra (emicizumab-kxwh) prophylaxis every week or every two weeks showed a 96 percent reduction and 97 percent reduction in treated bleeds, respectively. That testing was against no prophylaxis. In a subset of patients in the HAVEN 3 study who previously received factor VIII prophylaxis, the standard of care, HEMLIBRA reduced bleeds by 68 percent compared to their prior therapy. Additionally, data from the HAVEN 3 trial showed 55.6 percent of people treated with Hemlibra every week and 60 percent who were treated every two weeks experienced zero treated bleeds, compared to 0 percent of people treated with no prophylaxis.

In April the FDA granted Breakthrough Therapy Designation to Hemlibra for people with hemophilia A without factor VIII inhibitors, based on data from the HAVEN 3 study.

In Genentech’s HAVEN 4 study data showed that dosing with Hemlibra every four weeks provided clinically meaningful control of bleeding in people with or without factor VIII inhibitors. Genentech said the HAVEN 4 results show that administration of Hemlibra once per month can provide clinically meaningful control of bleeding in people with hemophilia A with or without factor VIII inhibitors.

Sandra Horning, Genentech’s chief medical officer and head of Global Product Development, said the data from the two trials show Hemlibra controls bleeds in hemophilia A patients and offers the “flexibility of less frequent subcutaneous dosing options.” That flexibility is a selling point that Genentech is touting. In a previous interview Dr. Gallia Levy, head of Hemlibra research at Genentech, told BioSpace that the less frequent dosing will help improve quality of life for patients. Before Hemlibra was approved, Levy said the hemophilia patients had to receive intravenous infusions every few days.

The data from the HAVEN 3 and HAVEN 4 trials, combined with data from two previous Phase III studies, reinforces the overall efficacy and safety of Hemlibra in the care for people with hemophilia A, Horning said.

Genentech is taking the data from the two latest trials and plans to submit them to regulatory agencies for expanded approval of its hemophilia drug. With expanded approval, analysts predict that Hemlibra could generate up to $5 billion annually for the Roche subsidiary.

Hemlibra was approved in November 2017 by the U.S. Food and Drug Administration. It was the first medication approved in 20 years for Hemophilia A with inhibitors. In December Genentech showed off long-term data from its HAVEN 1 and HAVEN 2 trials at the American Society of Hematology meeting. The longer-term data shows that more patients continued to experience zero bleeds with Hemlibra prophylaxis compared to their prior prophylaxis or on-demand BPA treatment. Updated data from HAVEN 2 showed 94.7 percent of children with hemophilia A with inhibitors who received Hemlibra prophylaxis had zero treated bleeds. Updated data from the HAVEN 1 study showed an 88 percent reduction in treated bleeds in adults and adolescents.

Hemlibra does come with a boxed warning due to potential blood clots in patients. Genentech has included guidelines in dosing protocols to address those concerns.

https://bit.ly/2kbdjhD

4 Companies with FDA Decisions This Week

There are several companies facing decisions by the U.S. Food and Drug Administration (FDA)this upcoming week. However, it should be noted that because the upcoming weekend is the Memorial Day holiday in the United States, some of these decisions may be made before their dates to avoid the holiday. Here’s a look.

Dova Pharmaceuticals.

On Monday, May 21, the FDA is expected to make a decision on Dova Pharmaceuticals‘ New Drug Application (NDA) for avatrombopag for thrombocytopenia in patients with chronic liver disease (CLD) who are scheduled to undergo a procedure. The submission was built on two identically-designed Phase III clinical trials, ADAPT 1 and 2. Avatrombopag met all primary and secondary endpoints with high statistical significance.

The application was accepted under a Priority Review status, which moved the review time from 10 months to a goal of six months. The drug is a second generation orally administered TPO-RA.

In a November 2017 statement, Alex Sapir, president and chief executive officer of Dova, said, “We are extremely pleased that FDA has accepted our NDA submission with Priority Review. We believe that avatrombopag represents a novel treatment option with robust efficacy as well as an improved safety profile when compared to platelet transfusions, today’s current standard of care. We look forward to working closely with FDA through the review process.”

BioMarin Pharmaceutical.

BioMarin, headquartered in San Rafael, California, is awaiting an FDA decision on its Biologics License Application (BLA) for pegvaliase, a PEGylated recombinant phenylalanine ammonia lyase enzyme product to treat adults with phenylketonuria (PKU) who have problems controlling their blood phenylalanine levels despite previous treatment with available therapeutics, including sapropterin. The PDUFA goal date is Friday, May 25.

The drug is also being evaluated by the European Medicines Agency (EMA). In a March 28 statement, Hank Fuchs, president of worldwide research and development for BioMarin, said, “The acceptance of the pegvaliase application for review by the EMA signifies a milestone in our journey to bring this important treatment to patients and families worldwide, offering a new option with the potential to alter the course of lifelong PKU management. For more than 10 years, we have been committed to advancing the development of therapies for the PKU community, and we look forward to working with European regulatory authorities on the pegvaliase application.”

Recro Pharma

Based in Malvern, Pennsylvania, Recro has a PDUFA date of Saturday, May 26 for its New Drug Application (NDA) for intravenous meloxicam 30mg to manage moderate to severe pain. The IV formulation was designed using the NanoCrystal platform, which allows for enhanced bioavailability of poorly water-soluble drugs. NanoCrystal is a registered trademark of AlkermesPharma Ireland Limited (APIL).

Amgen

The FDA has assigned Amgen a PDUFA action date of Monday, May 28, which happens to be Memorial Day in the U.S., for its supplemental BLA (sBLA) for Prolia (denosumab) to treat patients with glucocorticoid-induced osteoporosis (GIOP). The sBLA was submitted on July 28, 2017, and utilized data from a Phase III clinical trial comparing Prolia to risedronate in patients receiving glucocorticoid treatment. Glucocorticoid drugs that are often used to treat inflammatory conditions have numerous side effects, including bone loss.

“We believe that Prolia can address a critical treatment need for patients with glucocorticoid-induced osteoporosis, which is the most common drug-induced form of the disease,” said Sean Harper, Amgen’s executive vice president of research and development in an October 2017 statement. “We will continue to work closely with the FDA as they review our application and look forward to expanding Prolia’s benefits to patients with this serious condition that is often underestimated and untreated.”

https://bit.ly/2kbW3J2