Pakistan probes distributors of Roche cancer drug after patients go blind

 Pakistan said on Monday it was investigating two local distributors of Swiss pharmaceutical company Roche's Avastin cancer drug after 12 diabetic patients injected with the drug went blind.

The Drug Regulatory Authority of Pakistan (DRAP) said the health authorities in Punjab, the most populous province, had launched the investigation into local use of the drug Avastin, which is licensed for use in Pakistan.

"Incidents of loss of vision in diabetic patients have been reported following treatment with Altered/Dispensed/Diluted Avastin injection," the regulator said in a statement.

Javed Akram, the province's Minister for Specialised Health, said police were questioning two men they believe to be the drug's distributors in the state.

"A high level committee has been constituted to probe the issue. A case has been registered against the distributor and his aide," Akram said.

Following the incidents, the DRAP instructed the importer to recall the suspected batches of Avastin 100mg injection, which it said had been created illegally.

"The sale/distribution of registered Avastin injection has been put on halt till verification of its quality through sampling and laboratory testing to safeguard public health," it said in a statement on its website.

On its website, Roche said Avastin was approved in more than 130 countries, including the United States, to treat several types of cancer.

"Roche strongly condemns this criminal act of counterfeiting and is doing everything in its power to cooperate with the authorities to protect patients from counterfeits," said Roche in a statement to Reuters.

"In Pakistan, the vision loss from Avastin has been identified by the authorities as a case of contamination by a third party supplier," it added.

The regulator said in its statement that in the cases concerned Avastin had been used off-label, meaning outside its approved use, to treat diabetes-related eye conditions.

Cancer drug Avastin, when used at much lower doses, is similar to eye drug Lucentis and is used in many countries as a low-cost option to treat certain blindness-causing conditions.

In its statement, Roche said: "Avastin is not approved for any use in the eye. Counterfeit medicines pose a health risk to patients because their content may be ineffective and contain harmful ingredients."

Alam Sher, Punjab's deputy drug controller who filed the police complaint against the distributors, told Reuters that some companies buy Avastin and repackage it in smaller doses to make it more affordable for patients.

A sharp drop in the value of the local currency against the U.S. dollar has inflated the price of drugs in Pakistan, many of which are either imported or based on imported ingredients. Record high inflation has also diminished the purchasing power of many people.

https://news.yahoo.com/pakistan-bans-roche-cancer-drug-092010146.html

Ascletis to start phase 3 for Recurrent Glioblastoma

  Ascletis Pharma Inc. (HKEX: 1672, "Ascletis") today announces the completion of enrollment of 120 patients in the Phase III registration clinical trial of ASC40 combined with bevacizumab for treatment of recurrent glioblastoma (rGBM). ASC40 is an oral, selective small molecule inhibitor of fatty acid synthase (FASN), a key enzyme which regulates de novo lipogenesis (DNL). ASC40 inhibits energy supply and disturbs membrane phospholipid composition of tumor cells by blocking de novo lipogenesis ^[1].

The Phase III registration clinical trial (ClinicalTrials.gov Identifier: NCT05118776) is a randomized, double-blind, placebo-controlled, multi-center clinical trial in China to evaluate progression-free survival (PFS), overall survival (OS) and safety of patients with rGBM. Approximately 180 patients will be randomized at the ratio of 1:1 to Cohort 1 (oral ASC40 tablet, once daily + Bevacizumab) and Cohort 2 (matching placebo tablet, once daily + Bevacizumab). Based on prespecified interim analysis condition, 120 patients are likely to lead sufficient events for interim analysis of PFS. The interim analysis will be conducted after 93 PFS events are observed.

Glioblastoma (GBM) is the most aggressive diffuse glioma of astrocytic lineage and is considered a grade IV glioma based on the World Health Organization (WHO) classification ^[2]. Research shows that glioblastoma (GBM) accounts for 57% of gliomas and has an incidence rate of approximately 2.85 to 4.56 per 100,000 population in China per year, suggesting approximately 40,000 to 64,000 new cases of GBM per year ^[3]. In the U.S., GBM represents 56.6% of gliomas and has an incidence rate of approximately 3.21 per 100,000 population per year ^[4]. Over 90% GBM patients will relapse after surgery, radiation and chemotherapies. Effective treatments are extremely limited for patients with rGBM.

https://www.biospace.com/article/releases/ascletis-announces-completion-of-enrollment-of-120-patients-in-the-phase-iii-clinical-trial-of-fasn-inhibitor-asc40-combined-with-bevacizumab-for-treatment-of-recurrent-glioblastoma/

Generic Drugmakers Fall Short for Poorest Patients

• Analysis examined 50 medicines from five large manufacturers
• Some essential drugs still inaccessible despite price declines

 Efforts by major generic drugmakers to expand access to essential medicines have fallen short for many of the world’s poorest patients, a new study found.

Only one of out 50 products made by five large generic drug makers — Cipla Ltd., Hikma Pharmaceuticals Plc, Sun Pharmaceutical Industries Ltd., Teva Pharmaceutical Industries Ltd. and Viatris Inc. — had a pricing strategy that took into account a patient’s ability to pay in low-to-middle income nations, according the report from the Access to Medicine Foundation.

https://www.bloomberg.com/news/articles/2023-09-26/generic-drugmakers-fall-short-for-poorest-patients-report-says

US Dollar Emerges as Best Haven From American Government Shutdown Fears

 

• Yen, Swiss franc and gold are all dropping this month
• The bond rout is helping spur demand for the greenback

The greenback is once more proving it’s the only haven that matters.

Treasuries are cratering — and sending other bond markets down — as a looming shutdown underscores the potential that US fiscal profligacy will spur issuance. With the Federal Reserve determined to keep interest rates higher for longer, investors are finding few places to hide apart from the world’s reserve currency.

https://www.bloomberg.com/news/articles/2023-09-26/best-haven-from-us-shutdown-fears-looks-to-be-us-s-own-currency

Vaccination Offers 'No Meaningful Protection' Against Long COVID: Study

 by Marina Zhang via The Epoch Times (emphasis ours),

Findings in a new study challenge the mainstream narrative that COVID-19 vaccinations prevent long COVID. The study found that while previous infections reduce the risk of long COVID by 86 percent, vaccination status prior to COVID infection is irrelevant to a person's risk of developing long COVID.

“The notion had been that both previous infection as well as vaccination reduce the chances of subsequent long COVID should you become infected,” Dr. William Schaffner, professor of preventive medicine and health policy at Vanderbilt University Medical Center, told The Epoch Times.

These investigators have poured "cool water" on that concept, he continued.

Researchers from Martin Luther University Halle-Wittenberg, an over-500-year-old research university in Germany, found that people with the highest risk of long COVID or post-COVID condition, as the authors wrote, were unvaccinated people infected with the Wuhan variant, followed by unvaccinated and vaccinated participants infected with the alpha variant.

While not explicitly discussed in the study, the study’s diagram and supplementary tables showed that with the exception of infection with the Wuhan variant, unvaccinated people tend to have a slightly lower risk of long COVID than their vaccinated counterparts.

Furthermore, unvaccinated people infected with the omicron variant had the lowest risk of long COVID.

“Vaccination offered no meaningful protection against developing PCC [post-COVID condition] in case of an infection. In contrast, there was … strong evidence that a previous infection reduced the risk of PCC,” the authors wrote.

Based on Online Questionnaire

Nearly 49,000 people in the German population responded to the survey. Participants were recruited through postal mail. They were then asked to fill out an online questionnaire that included a list of symptoms.

Participants self-reported if they tested positive for COVID-19 and the symptoms they experienced afterward.

The study authors asked for symptoms present from the four- to 12-week post-infection window and for symptoms that persisted after the 12th week. Symptoms that did not persist beyond that were not deemed as long COVID.

Depending on the date of infection, the authors categorized the participant as being infected by the dominant variant at the time.

“We categorized infections before January 1, 2021 as caused by the Wildtype (Wuhan) variant, infections between January 1, 2021 and June 30, 2021 as caused by the Alpha variant, infections between July 1, 2021 and December 20, 2021 as caused by the Delta variant, and infections from December 21, 2021 as caused by the Omicron variant,” the authors wrote.

Of all the surveyed people, around 17,000 had at least one COVID-19 infection, with around 2,800 reporting long-COVID symptoms.

None of the participants in the study was physically examined nor did they present lab tests on their health.

Doctors are engaged in a debate over the study's findings and its methodology.

Many were concerned that the questionnaire was too subjective. Like many large population-based studies, the findings are provocative, "but they're often not definitive. You have to do other follow-up studies, many of which are much smaller but much more precise, and they eliminate a lot of the uncertainty," Dr. Schaffner said.

Dr. Cody Meissner, a professor of pediatrics at the Dartmouth Geisel School of Medicine, argued that the study's participant is "so heterogeneous" and that he is not sure what to conclude from the study.

As the study authors admit, none of the participants was given an actual diagnosis of long COVID nor tested for comorbidities. It is possible that any of the patients could have been suffering from another disease that may have been unrelated to COVID-19.

Long COVID Is Hard to Define

Another major problem plaguing long-COVID research is that everyone has a different definition of long COVID.

"There is a post-COVID symptomatology ... But I don't think we understand the biological basis; we can't define it very clearly. So to make a statement that it was more or less common after certain variants or vaccines is pretty difficult," Dr. Meissner said.

Retired associate professor of Brown University Dr. Andrew Bostom agreed that the long-COVID condition is poorly defined in the literature, so it is hard to conclude if the symptoms are long COVID or if it is something else entirely.

Apart from the loss of smell and taste, all other symptoms that characterize the long-COVID condition can manifest through psychosomatic triggers, Dr. Bostom said.

The study's findings "look interesting, particularly to people like me that have been disappointed in how such short shrift was given to natural immunity," Dr. Bostom, who has extensive experience working on pharmaceutical clinical trials, told The Epoch Times. But it's hard to conclude prior infection is protective against long COVID "if you're not really sure what the post-COVID condition is."

Study Findings Validate What Some Doctors See

Dr. Joseph Varon, chief of the Critical Care and COVID-19 Department at the United Memorial Medical Center, told The Epoch Times that he can look past the flaws in the methodology since the study findings validate what he sees in his clinic.

The study did not discuss if vaccinations put people at risk of long COVID. Its graph showed that the vaccinated cohort tended to have a slightly higher risk of long COVID than the unvaccinated, when they were infected by the same variant.

Dr. Varon interpreted this to suggest that vaccinations may put people at a greater risk of long COVID, which is what he has been seeing in his clinic.

"What I'm seeing is that the higher the number of boosters that you have, the more chances ... you're going to have long haul syndrome," he said, adding that the majority of his long-haul patients are those who took four or more doses of the vaccine rather than those who took up to three doses or were unvaccinated.

Dr. Varon also found that the study's findings on the most prevalent symptoms very accurately mirror what he sees in his clinic, with fatigue and cognitive impairment being the most common symptoms among his patients.

Psychiatrist Dr. Adonis Sfera at Patton State Hospital agreed that the study's symptoms are mostly representative of what he sees in his clinic, though the primary symptoms are fatigue and shortness of breath.

He also agreed with the notion that more vaccinations may put people at risk of long-haul symptoms since the vaccinations would induce the production of more spike proteins, which can cause organ damage and symptoms.

"The vaccines make our cells express the spike antigen. So the more vaccinated you are, the more likely you are to express the antigen," he said.

Hide Vaccine Injuries From Scrutiny?

Nurse practitioner Scott Marsland, who shares the Leading Edge Clinic, a long-COVID and vaccine-injury practice, with pulmonary critical care physician Dr. Pierre Kory, expressed concern that the study findings may hide vaccine injuries from scrutiny.

"[The paper] helps perpetuate the narrative that ... it doesn't make a difference whether or not [someone] got the vaccine; it's all about whether or not they got infected and which variant they got," Mr. Marsland said.

Long COVID and vaccine injury can share very similar symptoms, but detailed patient records would show that the symptoms appeared after different exposures.

Mr. Marsland was concerned that the study dismisses the cumulative effects the vaccines may have on patients, which contradicts what he sees in his clinic.

Some of his patients developed mild symptoms after their first or second shot, but they did not link it temporally to the vaccines until "they got the booster or a second booster" and their symptoms became severe, he said.

https://www.zerohedge.com/covid-19/vaccination-offers-no-meaningful-protection-against-long-cov dy id-study

Pliant to Discuss Interim Results of Phase 2a Trial in Primary Sclerosing Cholangitis

 Pliant Therapeutics, Inc. (Nasdaq: PLRX) today announced it will host a conference call and webcast on Tuesday, September 26, 2023 at 8:00 a.m. ET | 5:00 a.m. PT to discuss the interim results from the INTEGRIS-PSC Phase 2a trial. Members of Pliant’s management will be joined by Gideon Hirschfield, FRCP, Ph.D., Lily and Terry Horner Chair in Autoimmune Liver Disease at the University of Toronto and a principal investigator in the INTEGRIS-PSC trial.

The conference call will be simultaneously webcast online and will be accessible from the Events & Presentation section of Pliant’s website. The live audio of the conference call can be accessed by telephone by registering in advance at the following link: Pliant Therapeutics INTEGRIS-PSC Conference Call. Upon registration, all telephone participants will receive the dial-in number along and a unique passcode to access the call. An archived replay of the webcast will be available on Pliant’s website for 60 days following completion of the event.

https://finance.yahoo.com/news/pliant-therapeutics-host-investor-call-200500884.html

Merck Covid drug linked to virus mutations that can spread between people

 A new study released Monday said Merck

’s widely used antiviral Covid pill can cause mutations in the virus that occasionally spread to other people, raising questions about whether the drug has the potential to accelerate Covid’s evolution. 

The findings may increase scrutiny about the usefulness of the treatment, molnupiravir, which was one of the first Covid drugs available to doctors worldwide during the pandemic.

Molnupiravir works by causing mutations in Covid’s genetic information, which weakens or destroys the virus and reduces the amount of Covid in the body. However, the study published Monday in the scientific journal Nature found that Covid can sometimes survive treatment with molnupiravir, leading to mutated versions of the virus that have been found to spread to other patients. 

Researchers in the U.S. and U.K. specifically analyzed 15 million Covid genomes to see which mutations had occurred and when. They found that mutations increased in 2022 after molnupiravir was introduced in many countries. 

There is no evidence that molnupiravir, sold under the brand name Lagevrio, has produced more transmissible or severe variants of Covid, according to the study. 

But the findings are important for regulators who continue to assess the risks and benefits of molnupiravir, wrote Theo Sanderson, the lead author of the study and a researcher at the Francis Crick Institute in London, in a post on X, formerly Twitter.

A spokesperson for Merck pushed back on the new study, claiming the researchers assumed that the mutations they analyzed were associated with molnupiravir-treated patients “without documented evidence of that transmission.”

“Instead, the authors rely on circumstantial associations between the region from which the sequence was identified and timeframe of sequence collection in countries where molnupiravir is available to draw their conclusion,” the spokesperson said.

The spokesperson added that genomes with the mutations were “uncommon and were associated with sporadic cases.” 

The company in February also disputed an earlier study by the same team of researchers, which suggested that molnupiravir is giving rise to new mutations of the virus in some patients. Based on data at the time, a spokesperson for Merck said it didn’t believe molnupiravir was likely to contribute to Covid mutations.

The new study comes as Covid once again gains a stronger foothold in the U.S., primarily driven by newer strains of the virus.

But the U.S. and other countries appear to be relying less on molnupiravir to fend off Covid this year: Sales of the drug dropped to around $200 million during Merck’s third quarter, down 83% from the more than $1 billion reported during the same period a year ago. 

Merck’s molnupiravir has long been controversial because of its ability to cause genetic mutations. 

The U.S. Food and Drug Administration first approved the drug for emergency use in late 2021. But the FDA recommends against using Lagevrio during pregnancy because non-clinical studies suggest that it may cause fetal harm.

Molnupiravir also isn’t authorized for use in patients under 18 because it may affect bone and cartilage growth.

https://www.cnbc.com/2023/09/25/merck-covid-drug-linked-to-virus-mutations-study-says-.html