Alteogen Gets FDA OK on Orphan Drug Tag for Gastric Cancer Antibody-Drug

Alteogen Inc. (KOSDAQ: 196170) announced that it has successfully got an approval for orphan drug designation from the US Food and Drug Administration (FDA) with one of its assets (ALT-P7) for gastric cancer (designation letter 18-6439) last week. ALT-P7 is an antibody-drug conjugate (ADC) using a Trastuzumab variant form of antibody, and this approval would guarantee Alteogen the market exclusivity rights for seven years after FDA’s approval of ALT-P7 for gastric cancer treatment.

The FDA designation of orphan drug is designed to support the development and approval of drugs for the treatment of rare diseases or life-threatening illnesses. Products designated as orphan drugs would be recognized for not only market exclusivity after FDA approval, but also get additional benefits, such as tax benefit of the total costs for clinical trial studies, scientific advice meetings with FDA during the development process, and waiver of marketing application user fees.

ALT-P7, a candidate ADC treatment drug for gastric and breast cancers, is an anti-cancer ADC utilizing the company’s unique “NexMab^TM” platform technology, a proprietary next-generation site-specific conjugation methodology developed by the company. The related patents are registered in seven countries so far.

ALT-P7 is currently undergoing a first-in-human phase 1 clinical trial for breast cancer patients in Korea, after the investigational new drug (IND) approval last year from the Ministry of Food and Drug Safety (MFDS) of Korea (NCT03281824). Alteogen is planning to start phase 2 clinical trial for breast cancer patients in 2019. Following the current breast cancer trial, Alteogen will extend the clinical development of ALT-P7 for gastric cancer as well, which already has proven efficacy in pre-clinical in vitro and in vivo studies.

“The orphan drug designation of ALT-P7 by the US FDA will accelerate the advancement of gastric cancer treatment in the US,” said Dr. Soon Jae Park, Ph.D., CEO of Alteogen. “We believe that ALT-P7 can provide a breakthrough in the treatment of Her-2 overexpressing gastric cancer, for which there is no effective target treatment yet”.

https://bit.ly/2AN0s0f

Aridis Pharmaceuticals Launches Proposed Initial Public Offering

Aridis Pharmaceuticals, Inc. a biopharmaceutical company focused on the discovery and development of targeted immunotherapy using fully human monoclonal antibodies, or mAbs, to treat life-threatening infections, today announced that it has launched an initial public offering of 2,000,000 shares of its common stock. In addition, Aridis has granted the underwriters a 30-day option to purchase up to 300,000 additional shares of common stock at the public offering price, less the underwriting discounts and commissions. All of the shares to be sold in the proposed offering will be offered by Aridis. The initial public offering price is expected to be between $13.00 and $15.00 per share. Aridis has applied to list the shares on the Nasdaq Capital Market under the symbol “ARDS.” Cantor Fitzgerald & Co. is acting as sole book-running manager for the offering. Maxim Group LLC is acting as lead manager and Laidlaw & Company (UK) Ltd., Northland Securities, Inc. and Seaport Global Securities LLC are acting as co-managers for the offering. https://bit.ly/2vJ1XXH

Electroacupuncture Shows Benefits in Diabetic Peripheral Neuropathy

Electroacupuncture is effective and safe in the treatment of painful diabetic peripheral neuropathy (PDN), offering a nonpharmacologic option for the persistent pain, according to results of the first multicenter randomized controlled trial on the issue.

“The results of this study demonstrate that electroacupuncture treatment is effective

for reducing pain and improving sleep disturbance and quality of life in PDN,” the authors report.

The study was published recently in Diabetes Care and conducted by Kyung-Min Shin and colleagues from the Clinical Medicine Division, Korea Institute of Oriental Medicine, in Daejeon, South Korea. It involved 126 patients recruited from June 2014 to March 2015 with type 2 diabetes, a 6-month or longer history of PDN, and a mean weekly pain score of 4 or higher on the Pain Intensity Numerical Rating Scale (PI-NRS).

Electroacupuncture Was Well Tolerated and Safe

The patients were randomly assigned to a group receiving twice-weekly treatments of electroacupuncture or a control group for 8 weeks. Both groups also received an educational brochure on diet and lifestyle modification for diabetes.

The acupuncture treatments involved a mixed current of 2 Hz/120 Hz, delivered at 12 acupuncture points and 1 optional additional acupuncture point, established by the World Health Organization.

At the 8-week follow-up assessment, 9 participants in the electroacupuncture group and 19 in the control group had dropped out.

In terms of the primary outcome of pain, measured by the PI-NRS score at the ninth week of follow-up, patients receiving electroacupuncture showed significantly greater improvement compared with the control group (P = .01).

Of those in the treatment group, nine (15.52%) were responders, defined as achieving a reduction of 50% or greater on the PI-NRS, compared with just three (6.25%) in the control group (P = .21).

Those receiving electroacupuncture also had significantly greater improvements in pain, as measured by the short-form McGill Pain Questionnaire; their sleep interference, which is a common problem with PDN, also improved, as did pain scores assessed by EuroQol-5 Dimensions, after 9 weeks (P < .05).

And as many as 82.5% in the electroacupuncture treatment group reported improvements in Patient Global Impressions of Change compared with 34.1% in the control group, and the improvement was maintained through 17 weeks.

The specific acupuncture treatment points in the study included bilateral Zusanli (ST36), Xuanzhong (GB39), Yinlingquan (SP9), Sanyinjiao (SP6), Taichong (LR3), and Zulinqi (GB41); the additional acupuncture point of Bafeng (EX-LE10) was also available as an option.

There were no significant differences between the groups in terms of age, sex, duration of diabetes (12.53 years in the electroacupuncture group and 11.32 years in the control group), pain duration (electroacupuncture group, 3.81 years; control group, 3.23 years), and use of antidiabetes medication.

Patients in both groups were permitted to take rescue medication of acetaminophen 500 mg, with a maximum dosage of 3000 mg per day, but no other analgesic medication was allowed. The consumption of the medications did not differ throughout the study.

The groups also remained on stable doses of their antidiabetes medications.

No safety issues were reported with electroacupuncture, and the two groups had an equal incidence of adverse events (n = 12) and serious adverse events (n = 3 each).

“Electroacupuncture treatment was well tolerated and safe during this study,” the authors say.

They noted that the study is the first randomized trial of its kind: “To our knowledge, this is the first multicenter randomized controlled trial to evaluate the effectiveness and safety of electroacupuncture treatment for the management in PDN.”

“These findings suggest that  [the] treatment may be recommended as a non-pharmacological treatment for pain reduction in PDN.”

Lack of Effective Comparator Remains a Limitation for Acupuncture Research

With electroacupuncture, a small electric current is passed between two acupuncture needles to deliver stimulation. As previously reported by Medscape Medical News, a pilot study showed that traditional acupuncture improved chemotherapy-induced peripheral neuropathy related to breast cancer treatment — a serious problem shown to occur in nearly 50% of women, sometimes for years after treatment.

The authors of that study and the current study, however, each acknowledge the important limitation of a lack of a sufficient placebo or sham group to serve as an active control, and they note that the nature of an effective comparator remains a challenge in acupuncture research.

The study received support from the Korea Institute of Oriental Medicine. The authors have disclosed no relevant financial relationships.

Diabetes Care. Published online July 30, 2018.  Abstract

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Obese kids: Not all hope is lost

For many young children who are obese, the future might not be as grim as previously thought, a University of Michigan study suggests.

According to U-M researchers, one-third of U.S. children with obesity in kindergarten achieve a lower weight status at least once through childhood, and 22 percent of these kids experience persistent remission of obesity—achieving and maintaining a lower weight status—by 8th grade.

“Hope is not lost. A meaningful number of young children with obesity are able to experience remission overtime,” said senior researcher Katherine Bauer, assistant professor in the Department of Nutritional Sciences at the U-M School of Public Health.

Bauer said she wanted to understand the remission of childhood obesity after reading a 2014 study in the New England Journal of Medicine that showed the majority of children with obesity by kindergarten continued to experience obesity throughout childhood.

Understanding how some kids achieved a nonobese weight status over time may shed light on how we can help all children with obesity, she said.

Bauer and colleagues Danny Luan, a recent U-M graduate, and Briana Mezuk, associate professor of epidemiology at the School of Public Health, used the same dataset as the 2014 NEJM study but looked at it differently.

Using this nationally representative sample of more than 21,000 kindergartners, the U-M researchers did the opposite of what nearly all other studies tracking children’s growth have done. Instead of starting with all children and seeing who develops obesity, they started with the kids who had obesity in kindergarten and looked at what happened to them over time.

There were some distinct patterns among the children who experienced obesity remission, Bauer said. At first glance, girls and children from higher socioeconomic status families appeared more likely to be able to overcome early childhood obesity.

But after accounting for the fact that these children, while still experiencing obesity, had lower BMIs in kindergarten than their peers, these differences disappeared.

One thing that is clear was that kids who experienced remission gained much less weight over time than the children who remained obese, often gaining half or one-third as many pounds than their peers every two years, the study showed.

“We need to help limit children’s weight gain. Obesity is not something kids just grow out of by spurting up in height,” Bauer said. “These findings suggest that hope is not lost.

“Some children are able to experience remission even if they don’t participate in clinic-based weight management programs, which may be hard for some families to access. By continuing to understand children who experience obesity remission, we can identify creative ways to give children and families the support they need.”

Bauer said she hopes the findings provide hope for children and parents, and help mobilize communities to help all children become healthier.

The study is published in Pediatric Obesity.

 Explore further: Odds for weight loss are stacked against children who are obese early on 

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Surgical Price Transparency Tied to Improved Volume, Revenue

Ambulatory surgery centers experience increases in patient volume, patient satisfaction, and revenue after adopting price transparency, according to a study published recently in The American Surgeon.

Ambar Mehta, M.D., from Johns Hopkins University in Baltimore, and colleagues used data from six ambulatory surgery centers to characterize the impact of price transparency on a surgery center’s patient volume, revenue, and patient satisfaction.

The researchers found that five centers reported an increase in patient volume and revenue after adopting price transparency, with a median increase of 50 percent in patient volume at one year (range, 10 to 200 percent). An increase in revenue (median 30 percent) was reported by four centers (range, 4 to 75 percent). Three centers reported an increase of new third-party administrator contracts (average; seven contracts; range, two to 12 contracts). Three centers reported a reduction in their administrative burden. Five of the six centers reported an increase in patient satisfaction and patient engagement after the initiation of price transparency. Discouragement from other practices, hospitals, or insurance companies was the leading barrier to making prices transparent.

“The findings of this study provide important insights to medical providers in designing and implementing price transparency initiatives,” the authors write.

Abstract/Full Text (subscription or payment may be required)

https://bit.ly/2LYOXrS

New system allows rapid response to heart attacks, limits cardiac damage

Researchers from North Carolina State University and the University of North Carolina at Chapel Hill have developed a drug-delivery system that allows rapid response to heart attacks without surgical intervention. In laboratory and animal testing, the system proved to be effective at dissolving clots, limiting long-term scarring to heart tissue and preserving more of the heart’s normal function.

“Our approach would allow health-care providers to begin treating heart attacks before a patient reaches a surgical suite, hopefully improving patient outcomes,” says Ashley Brown, corresponding author of a paper on the work and an assistant professor in the Joint Biomedical Engineering Program (BME) at NC State and UNC. “And because we are able to target the blockage, we are able to use powerful drugs that may pose threats to other parts of the body; the targeting reduces the risk of unintended harms.”

Heart attacks, or myocardial infarctions, occur when a thrombus — or clot — blocks a blood vessel in the heart. In order to treat heart attacks, doctors often perform surgery to introduce a catheter to the blood vessel, allowing them to physically break up or remove the thrombus. But not all patients have quick access to surgical care.

And more damage can occur even after the blockage has been removed. That’s because the return of fresh blood to tissues that had been blocked off can cause damage of its own, called reperfusion injury. Reperfusion injury can cause scarring, stiffening cardiac tissue and limiting the heart’s normal functionality.

To address these problems, researchers have developed a solution that relies on porous nanogel spheres, about 250 nanometers in diameter, which target a thrombus and deliver a cocktail of two drugs: tPA and Y-27632.

A thrombus can be made of various substances, such as platelets or arterial plaques, but they all contain a substance called fibrin. So, to target blockages, each nanogel is coated with proteins that bind specifically to fibrin. In other words, when the nanogels reach a thrombus, they stick.

The tPA and Y-27632 are layered inside the nanosphere, with the tPA forming a shell that surrounds the Y-27632. As a result, the tPA leaks out first at the thrombus site, allowing it to do its job — which is to break down fibrin and dissolve the clot.

As the tPA is released, the Y-27632 escapes the nanogel. While the tPA targets the clot itself, the Y-27632 aims to limit the damage caused by reperfusion injury. It does this by limiting the rigidity of the cells in the area that contribute to scarring. This allows these cells to retain more of their plasticity, improving their ability to function normally and preserving more cardiac function.

In in vitro testing, the researchers found that the targeted tPA/Y-27632 cocktail dissolved clots in a matter of minutes. While this has yet to be tested in trials, it may work more quickly than surgical interventions, which require time to prep the patient and get the catheter in place.

In tests using laboratory rats, the researchers also found that their technique limited scarring and preserved heart function after heart attack better than targeted tPA or Y-27632 by themselves — and far better than a control group in which animals received neither drug.

Specifically, animals that received the targeted cocktail had a left ventricular ejection fraction, which measures a heart’s functionality, of around 67 percent four weeks after the heart attack — which is healthy. The tPA by itself was around 57 percent, which is at the low end of the normal range, while both the control group and Y-27632 by itself dipped into the 40s. Similarly, the targeted cocktail resulted in scar tissue across less than 5 percent of the affected area. The tPA and Y-27632 had scar tissue across approximately 7 percent of the area, with the control group seeing scarring across more than 10 percent.

What’s more, the researchers found that the targeted nanogels resulted in little or none of the nanogels being found in other tissues — such as the lungs and liver — particularly when compared to the use of the non-targeted nanogels.

“This is an important part of our findings, because tPA and Y-27632 can both pose risks if they begin acting on parts of the body outside of the targeted area,” Brown says. “For example, tPA can cause bleeding and Y-27632 can affect many tissues where cell contraction is needed for normal function.”

One other benefit of the targeted nanogels is that, due to their small size, they can target even those blood vessels that are too small to reach using catheters.

The researchers also note that this is a preclinical study. Next steps for the work include further evaluating the safety of the nanogels and testing in larger animal models.

“While we are still in the early stages of developing this technology, we know that it’s important to acknowledge issues related to cost,” Brown says. “Given the complexity of the drug delivery system, it should be comparable to or slightly more expensive than recombinant protein therapeutics currently in clinical use — such as tPA by itself. However, because the drugs are targeted, the doses are likely to be smaller. That should help to keep the costs comparable to existing drugs on the market.”

The paper, “Targeted Treatment of Ischemic and Fibrotic Complications of Myocardial Infarction Using a Dual-Delivery Microgel Therapeutic,” is published in the journal ACS Nano. Co-lead authors are Emily Mihalko, a Ph.D. student in the joint BME program, and Ke Huang, a Ph.D. student at NC State. The paper was co-authored by Ke Cheng, a professor of biomolecular sciences at NC State and a professor in the joint BME program, and by Erin Sproul, a former postdoctoral researcher in the joint BME program. All of the study authors are members of the Functional Tissue Engineering group of the Comparative Medicine Institute (CMI) at NC State, which facilitated this interdisciplinary collaboration.

The work was done with support from the NC State CMI; the National Institutes of Health, under grants HL123920 and HL137093; and the National Science Foundation under grant ECCS-1542015.

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Story Source:

Materials provided by North Carolina State University. Note: Content may be edited for style and length.

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Journal Reference:

1. Emily Mihalko, Ke Huang, Erin Sproul, Ke Cheng, Ashley C. Brown. Targeted Treatment of Ischemic and Fibrotic Complications of Myocardial Infarction Using a Dual-Delivery Microgel Therapeutic. ACS Nano, 2018; DOI: 10.1021/acsnano.8b01977

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Bayer OKd for new treatment regimen for Eylea in the EU

Bayer announced today that the European Commission has approved a new treatment approach for Eylea to enable clinicians to combine proactive treatment with early extension of the injection interval for patients with neovascular age-related macular degeneration (nAMD).

The new regimen allows clinicians already in the first year of treatment to extend patients’ individual injection intervals based on visual and/ or anatomic outcomes.

The new approach is based on results from the ALTAIR study, in which after 52 weeks 57% of patients had their next regularly scheduled Eylea injection at an interval of 12 weeks or more. Treatment intervals up to 16 weeks between injections have been studied. Patients participating in the study gained an average of up to 9.0 letters, including 50% of participants who gained 10 or more letters of vision at week 52, as measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) eye chart. These results were largely maintained during the second year, demonstrating the sustainability of this proactive approach.

‘Neovascular age-related macular degeneration can have a devastating impact on a patient’s life beyond the vision loss it causes,’ said Dr. Michael Devoy, Head of Medical Affairs & Pharmacovigilance of Bayer AG’s Pharmaceuticals Division and Bayer Chief Medical Officer. ‘This new treatment regimen for Eylea has the potential to reduce the number of injections and clinic visits to less than four in the second year for certain neovascular AMD patients, while still maintaining strong visual outcomes and the ability to see, this means that patients can spend more time doing what matters to them.’

The updated product information brings forward a proactive ‘Treat and Extend’ (T&E) dosing regimen. This offers physicians the option already in the first year of EYLEA treatment to extend their patients’ injection intervals by two- or four-weekly increments following initial dosing. If visual and/or anatomic outcomes deteriorate during the T&E dosing regimen, the treatment interval should be shortened accordingly. The initial doses are three consecutive monthly doses, followed by one injection after two months.

Worldwide, AMD is estimated to cause blindness in three million people, accounting for 8.7% of all blindness and 50% of blindness in the developed world, with neovascular AMD alone accounting for over 80% of legal blindness in all AMD patients. The risk of AMD increases with age, and with the number of people over 65 years of age expected to more than double from 390 million to 800 million by 2025, the number of individuals affected by neovascular AMD is also predicted to rise accordingly.

Eylea has been approved in the majority of countries for five indications to treat patients with: neovascular AMD (wet AMD), visual impairment due to diabetic macular edema (DME), retinal vein occlusion (RVO; branch RVO or central RVO) and myopic choroidal neovascularization. Eylea is the global market leader of anti-VEGF treatment, with estimated around 20 million doses administered worldwide since launch.

Bayer and Regeneron Pharmaceuticals Inc. are collaborating on the global development of Eylea. Regeneron maintains exclusive rights to Eylea in the United States. Bayer has licensed the exclusive marketing rights outside the United States, where the companies share equally the profits from sales of Eylea, except for Japan where Regeneron receives a percentage of net sales.

https://bit.ly/2vkHM2I