Molecule in the nervous system may hold key to treating chronic pain

 A newly published study by University of Calgary researchers reveals a potential new way to treat chronic pain using anti-cancer drugs rather than opioid-based pain medication.

By analysing a large number of genes important in the transmission of pain information to the brain, principal investigator Dr. Christophe Altier, PhD, who holds a Canada Research Chair in Inflammatory Pain, and his team have identified the existence of a molecule in the nervous system that enhances sensitivity to pain.

This molecule had previously been thought to play a role in cancer growth but had never been reported in the nervous system. It may now be possible to use already existing anti-cancer drugs to block pain.

"The most exciting part of this discovery is that we don't need to develop a new drug," says Dr. Christophe Altier, PhD, associate professor at the Cumming School of Medicine (CSM) and member of the Snyder Institute for Chronic Diseases at the CSM. "We've shown that an existing drug, approved in the treatment of cancer, can be repurposed to treat pain."

In the study on mice, Altier's team showed drugs commonly used for treating lung cancer and a type of brain cancer could be effective in controlling pain. The researchers specifically tested for pain resulting from nerve injury and inflammation and found the cancer drugs worked very well. The next step is to secure funding for clinical trials to see whether the same positive results will be experienced by people suffering from chronic conditions including abdominal pain and post surgery pain.

Because the drugs being used already exist and have been proven safe, the timeline for this treatment to become a reality will be shorter than if they had to develop new medications. Altier has already filed a patent application for this novel treatment with study co-author Dr. Gerald Zamponi, PhD, professor at the CSM and member of the Hotchkiss Brain Institute.

The discovery will be welcome news for chronic pain sufferers who in the future might have the option to stop taking potentially addictive opioids that require increases in doses over time to remain effective.

"With these anti-cancer drugs, there is no effect on tolerance," says Dr. Manon Defaye, PhD, first author on the paper. "We don't need to increase the dose of the drug to obtain pain relief."

Funding for this research came from the Canadian Institutes of Health Research and the Alberta Children's Hospital Research Institute.

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Story Source:

Materials provided by University of Calgary. Note: Content may be edited for style and length.

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Journal Reference:

1. Manon Defaye, Mircea C. Iftinca, Vinicius M. Gadotti, Lilian Basso, Nasser S. Abdullah, Melissa Cumenal, Francina Agosti, Ahmed Hassan, Robyn Flynn, Jeremy Martin, Vanessa Soubeyre, Gaëtan Poulen, Nicolas Lonjon, Florence Vachiery-Lahaye, Luc Bauchet, Pierre Francois Mery, Emmanuel Bourinet, Gerald W. Zamponi, Christophe Altier. The neuronal tyrosine kinase receptor ligand ALKAL2 mediates persistent pain. Journal of Clinical Investigation, 2022; DOI: 10.1172/JCI154317

https://www.sciencedaily.com/releases/2022/06/220613112123.htm

Beijing Halts Offline Sports Events From June 13 Due to COVID Outbreak

 Beijing will suspend all offline sports events starting from June 13 citing high transmission risks of a recent COVID-19 outbreak linked to a bar in the city, Beijing Municipal Bureau of Sports said in a statement on Monday.

As of June 12, some 166 cases have been linked so far to the outbreak at the Chaoyang Heaven Supermarket Bar, which emerged last week.

https://www.usnews.com/news/world/articles/2022-06-13/beijing-halts-offline-sports-events-from-june-13-due-to-covid-outbreak

Basaglar 'Copycat' Insulin for Diabetes Has Advantages Over Lantus

 The follow-on or copycat insulin glargine product Basaglar (Lilly) is similar to brand-name Lantus (Sanofi) in terms of efficacy and safety for the treatment of type 2 diabetes, but Basaglar cost less and had better adherence, new real-world data show.   

The findings, from a repository of US claims data for insured individuals from 14 commercial health plans and Medicare Advantage plans, were presented at the American Diabetes Association (ADA) 82nd Scientific Sessions by Xiaoxue Chen, MPH. The results were also published June 7 in Diabetes, Obesity and Metabolism.

Insulin expenditures more than tripled from 2001 to 2014 in the United States, according to data from the Medical Expenditure Panel Survey and Medicaid, due to lack of competition and difficulties developing generic versions. Basaglar was approved as a biosimilar insulin glargine by the European Medicines Agency in 2014 and as a follow-on insulin glargine to Lantus by the US Food and Drug Administration in 2015.

Although Basaglar offers an opportunity to reduce costs and improve adherence to insulin products, some clinicians and patients have expressed concern that biosimilar/follow-on products might differ from the branded version in terms of stability, efficacy, or immunogenicity.

"While clinical trials demonstrated noninferiority of Basaglar to Lantus, this does not necessarily replicate in the real world," noted Chen, a research scientist at Anthem in Wilmington, Delaware.

However, the results of this new real-world head-to-head study showed that Basaglar was similar to Lantus in terms of safety and effectiveness, but was associated with better adherence and drug cost savings.

"The findings highlight the potential that biosimilar/follow-on biologics offer in terms of expanding patient access and improving treatment affordability," she said.

Session moderator Rajesh Garg, MD, professor of medicine and director of clinical diabetes at the University of Miami, Florida, told Medscape Medical News: "It's reassuring and it's kind of nice that we're getting these biosimilars that are improving the availability of insulins."

Real-World Data Point to Basaglar Advantage

The study population included 1136 new Basaglar users and 6304 new Lantus users identified from paid pharmacy claims (91% commercial insurance and 9% Medicare Advantage) submitted between January 2017 and December 2018.

Those who took Basaglar tended to be younger than those who took Lantus (54.0 versus 56.3 years) and were slightly less likely to have comorbidities (52.2% vs 55.2%). Adjustments were made for age, sex, insurance type, region, comorbidities, baseline medical utilization and cost, baseline A1c, and baseline diabetes medications.

In the Basaglar group, A1c dropped from 9.6% at baseline to 8.5% 1 year after initiation, while in the Lantus group, A1c dropped from 9.2% to 8.2%. The adjusted difference of 0.17% was not significant and met the noninferiority criteria (0.4% margin).

"Both groups had similar and substantial reductions in A1c at 1 year," Chen said.

Adverse event rates were also similar. Hypoglycemic events occurred in 1.0% of patients with Basaglar versus 1.5% with Lantus, giving a nonsignificant adjusted odds ratio (OR) of 0.88 (P = .703). Vascular events also weren't significantly different, occurring in 7.6% of patients with Basaglar versus 9.4% with Lantus (OR, 1.13; P = .37).

Medication adherence, assessed using "proportion of days covered," with 80% or greater availability of a prescribed daily dose defined as adherent, was 42.4% for Basaglar versus 33.6% for Lantus, a significant difference (OR, 1.44; P < .001).

Medication persistence, defined as a refill gap of less than 45 days from the previous prescription fill, was higher at 1 year for Basaglar than Lantus (37.8% vs 30.9%; adjusted OR, 1.35; P < .001).

Total medical costs in the 1 year after initiation were $1056 higher with Lantus, although this wasn't significantly different from Basaglar after adjustment.

Total pharmacy costs were $2070 lower with Basaglar, a significant difference from Lantus, and imputed insulin costs were $462 lower with Basaglar, again a significant difference.

A limitation, Chen noted, was that net drug cost and patient out-of-pocket cost remained unknown because of drug rebates and consumer manufacturer coupons. 

Results were similar to the main findings in a sensitivity analysis of just the patients who used insulin pens. Basaglar is only available in pens whereas Lantus is also available in vials, and the increased convenience of pens might have affected adherence.

Is Competition Bringing Down the Cost Overall?

Chen pointed out that the availability of follow-on/biosimilar drugs is resulting in discounts in the price of the originator drugs as competition within the same indication intensifies.

Another factor was the introduction of the first "interchangeable" biosimilar insulin, Semglee (Mylan Pharmaceuticals), in July 2021, which means it can be substituted for Lantus at the pharmacy without the need for a separate prescription.

"As more biosimilars, such as Semglee, are introduced, increased price competition may result in lower costs. While costs are in part determined by contractual agreements among manufacturers, health insurers, and/or pharmacy benefit managers, savings introduced by these medications may be passed on to the consumer," Chen noted.

Indeed, Garg told Medscape Medical News that in his experience most insurance companies now cover Basaglar or Lantus because the price of Lantus has come down. "Basaglar can be more expensive. Many times I've had to switch from Basaglar to Lantus because that's what was preferred on the formulary," he said.

Chen is an employee of Anthem. Garg has reported no relevant financial relationships.

Diabetes Obes Metab. Published online June 7, 2022. Abstract

https://www.medscape.com/viewarticle/975440

WuXi AppTec Falls Sharply as Shareholders Plan to Sell Stake

 Shares of WuXi AppTec Co. declined sharply in Hong Kong Monday after its largest shareholder announced it planned to cut its stake.

Wuxi AppTec's Hong Kong-listed shares slumped up to 11% in early trade, and was last 10% lower at HK$94.35. The stock is on track for its worst one-day percentage loss since March.

Its A-shares were also 10% lower at CNY92.57.

The Chinese pharmaceutical company's controlling shareholder and others plan to sell up to 3% of the company, it said in a filing late Friday. The disposal, to be carried out between July 4 and Sept. 30, has been proposed due to the "capital needs" of selling shareholders, according to Wuxi AppTec. The shares will be sold by either bidding or block trading, it said.

Wuxi AppTec is mainly owned by a consortium which holds about 23% of the company.

The planned disposal is "the key reason for the selldown today for Wuxi AppTec," UOB Kay Hian analyst Carol Dou said. The fact that "the largest shareholder is reducing its shareholding" has hurt investor sentiment, Ms. Dou said. But the wider market is also weak, and the company's operations are solid, she added.

https://www.marketscreener.com/quote/stock/WUXI-APPTEC-CO-LTD-44403583/news/WuXi-AppTec-Falls-Sharply-as-Shareholders-Plan-to-Sell-Stake-40704951/

NRx Down After FDA Denies Breakthrough Therapy Designation

 NRx Pharmaceuticals Inc. shares were down 8%, to 53 cents, after the company said the U.S. Food and Drug Administration denied the Breakthrough Therapy designation request for Zyesami (aviptadil) for patients with Covid-19.

The stock declined 58% on May 26 after unfavorable results from a Zyesami study.

NRx has said it would evaluate options for Zyesami in protecting the lung in other respiratory disorders and in other therapeutic areas. NRx has focused on NRX-101 for treatment of severe bipolar depression in patients with acute suicidal ideation and behavior.

https://www.marketscreener.com/quote/stock/NRX-PHARMACEUTICALS-INC-38908842/news/NRx-Pharmaceuticals-Down-8-After-FDA-Denies-Breakthrough-Therapy-Designation-40711601/

CRISPR Tx Shares Fall as bluebird's Gene Therapy Soars

 Shares of CRISPR Therapeutics fell more than 11% on Monday as investors reacted negatively to the endorsement of a rival beta-thalassemia gene therapy developed by bluebird bio.

Last week, the U.S. Food and Drug Administration’s Cell, Tissue and Gene Therapies Advisory Committee unanimously supported bluebird’s beti-cel, a one-time gene therapy for patients with transfusion-dependent beta-thalassemia, a rare, inherited blood disorder caused by a genetic defect in hemoglobin.

Beti-cel, also known as betibeglogene autotemcel, is marketed in Europe as Zynteglo. Late-stage clinical data showed that 89% of patients who could be evaluated achieved transfusion independence following treatment with beti-cel, and safety data has been positive. The FDA is expected to give its final verdict on beti-cel by Aug. 19.

One day after the advisory committee endorsed beti-cel for beta-thalassemia, CRISPR Therapeutics and its partner Vertex Pharmaceuticals released positive data for their gene therapy candidate, exa-cel. Exa-cel is a CRISPR-Cas9-based gene editing therapy for both transfusion-dependent beta-thalassemia (TDT) and severe sickle cell disease (SCD).

Data shared by the companies showed that 42 of 44 patients with TDT who received exa-cel have remained transfusion free for up to 37.2 months. The two patients who were not transfusion free had 75% and 89% reductions in transfusion volume, the companies said.

In SCD, the data was also positive. All 31 patients with sickle cell disease that is characterized by recurrent vaso-occlusive crises (VOCs) were free of the events following treatment with exa-cel. Data showed the patients had a duration of up to 32.3 months, CRISPR and Vertex reported, which expanded their partnership in this space last year.

Carmen Bozie, head of global medicines development and medical affairs at Vertex, touted the data. Bozie noted that of the 75 patients treated with exa-cel, 33 have one year or more of follow-up after infusion with the gene therapy. The data demonstrate the potential of exa-cel as a one-time functional cure for patients with transfusion-dependent beta-thalassemia or severe sickle cell disease, she said in a statement.

While bluebird’s beti-cel was largely free of serious adverse events, Vertex and CRISPR reported that two of the 44 TDT patients experienced an SAE. One of the patients experienced three serious events that were connected to exa-cel, as well as busulfan, which was administered along with the gene therapy. That patient experienced hemophagocytic lymphohistiocytosis (HLH), a life-threatening condition related to excessive immune response, as well as acute respiratory distress syndrome and headache. The other patient experienced idiopathic pneumonia syndrome that was considered related to both exa-cel and busulfan, the companies said.

Among the 31 patients with SCD, there were no SAEs considered related to exa-cel.

CRISPR and Vertex are not alone in chasing bluebird bio to market with a gene therapy for beta-thalassemia. Editas Medicine is also developing its own gene therapy for the debilitating disease.

Earlier this year, Editas won Rare Pediatric Disease designation for its experimental beta-thalassemia gene therapy, EDIT-301. The therapeutic is designed to edit the HBG1/2 promoter to disrupt the binding site of BCL11a and ameliorate disease symptoms.

In May, EDIT-301 won Orphan Drug designation for the treatment of beta-thalassemia and SCD. Editas expects to initiate a Phase I/II study of EDIT-301 in patients with transfusion-dependent beta-thalassemia later this year.

https://www.biospace.com/article/shares-of-crispr-fall-as-bluebird-bio-s-gene-therapy-soars/

Sangamo resumed at Neutral by Wedbush

 Target $5

https://finviz.com/quote.ashx?t=SGMO