FDA lifts hold on Astellas’ Pompe gene therapy

 The FDA has delivered some good news to Astellas’ troubled gene therapy unit, lifting a clinical hold on its Pompe disease candidate AT845 and clearing the way for dosing of patients to resume.

The US regulator placed a hold on clinical testing of the gene therapy last June, shortly after a serious case of peripheral sensory neuropathy was reported in the phase 1/2 FORTIS trial in late-onset Pompe disease (LOPD).

That came amid a string of setbacks in Astellas’ gene therapy programmes, including a clinical hold imposed after cases of liver toxicity and deaths were in a trial of its AT132 gene therapy candidate for rare disease X-linked myotubular myopathy (XLMTM), and the halt of three candidates for Duchenne muscular dystrophy (DMD).

The company said it is “working on completing the clinical and regulatory activities necessary to resume dosing in the FORTIS clinical trial” and is looking forward to “the continued development of AT845 as an important potential new treatment for adults living with LOPD.”

AT845 uses an adeno-associated virus (AAV) vector to deliver a functional copy of the GAA gene coding for the enzyme acid alpha-glucosidase that doesn’t work properly in LOPD.

The hope is that a once-shot, intravenous treatment with AT845 can lead to expression of a functional form of the enzyme in tissues affected by the disease, including skeletal and cardiac muscle, and do away with the need for patients to receive regular injections with recombinant enzyme replacement therapies (ERTs) like Sanofi’s Lumizyme (alglucosidase alfa).

Signs that Astellas remained confident in the programme came earlier this month when the pharma group licensed a drug developed by Selecta Biosciences that will be used in combination with AT845 in a $350 million deal.

Selecta’s IgG protease drug IdeXork (Xork) will be used as a pre-treatment to overcome one of the key limitations to AAV-based gene therapies like AT845, namely that some patients have existing antibodies against the AAV vector that interfere with the treatment.

Meanwhile, Astellas has continued to invest in its gene therapy business with a series of investments, including the payment last October of $50 million for a 15% stake in US biotech Taysha, securing an option on clinical-stage, single-gene therapies for rare genetic diseases Rett syndrome and giant axonal neuropathy (GAN).

That came just a few months after the company entered into a $1.6 billion alliance with Dyno Therapeutics (back-ended with just $18 million upfront), as well as the $3 billion acquisition of Audentes Therapeutics in 2019, which was the foundation for its push into gene therapy.

https://pharmaphorum.com/news/fda-lifts-hold-on-astellas-pompe-gene-therapy/

Asco-GI 2023 – Keytruda looms over zanidatamab's second shot

 Zanidatamab looked good enough in Her2-amplified biliary tract cancers to persuade Jazz to part with $375m up front for the asset, but developing data in gastroesophageal adenocarcinoma must have helped seal the deal. The latest phase 2 update shows improvement on a prior cut presented at Esmo 2021, with the dual Her2 bispecific plus chemo generating an impressive 79% objective response rate. The data, which are still early, are tracking ahead of standard-of-care Herceptin plus chemo, and look at least as good as Keytruda/Herceptin/chemo in Keynote-811, a trial that won the triplet accelerated approval in 2021. This Keytruda combo generated results considered surprising, because the addition of PD-(L)1 blockade to Her2-targeting had not previously yielded much success. Could zanidatamab responses be improved by adding checkpoint inhibition? That question is being asked in the pivotal Herizon-GEA-01 trial, which reads out in 2024. Keytruda remains a threat, however, with full results from Keynote-811 expected any time. That result will provide the bar for Jazz and Zymeworks to beat, and given its burdensome diarrhoea side effect zanidatamab needs to impress to have a real chance to compete against the Merck machine.

Filling in the blanks in 1st-line Her2+ GEA
	Zanidatamab + chemo (ph2, n=42)	Keytruda + Herceptin + chemo (Keynote-811)**	Herceptin + chemo (Toga trial)
mOS	not reached*	?	13.8 months
mPFS	12.5 months	?	6.7 months
ORR	79% (CR~8%)	74% (CR=11%)	47%
mDOR	20.4 months	10.6 months	6.9 months
18-mth OS	84%	-	-
12-mth OS	88%	-	-
Notes: *median duration of study follow-up 26.5 months; **first interim analysis when the first 260 pts enrolled had ≥8.5 mo of follow-up, tested ORR. Source: Asco publications, company communications & clinicaltrials.gov. https://www.evaluate.com/vantage/articles/events/conferences-snippets/asco-gi-2023-keytruda-looms-over-zanidatamabs-second

Cosmos Health Extends and Updates Agreement to Acquire ZipDoctor

  Cosmos Health, Inc. ("the Company") (Nasdaq:COSM), a global healthcare group with proprietary lines of nutraceuticals and distributor of pharmaceuticals, branded generics, OTC medications and medical devices, announced today that it has extended and updated its previously issued non-binding letter of intent to acquire ZipDoctor Inc. from American International Holdings Corp (AMIH). Cosmos Health has successfully renegotiated the acquisition price of ZipDoctor to achieve much improved payment terms. The updated letter of intent will remain effective until February 15, 2023.

ZipDoctor Inc., a wholly owned subsidiary of American International Holdings Corp. (OTC: AMIH), is a direct-to-consumer subscription-based telemedicine platform, that expects to provide its customers affordable, unlimited, 24/7 access to board certified physicians and licensed mental and behavioral health counselors and therapists. ZipDoctor's online telemedicine platform will be available to customers across the United States and offers English and Spanish coverage with virtual visits taking place either via the phone or through a secured video chat platform. ZipDoctor customers will be able to subscribe through their website at www.ZipDoctor.co and are only required to pay a monthly fee, which is determined based on whether they are an individual, a couple, or a family.

Update on the ongoing review of COSM trading patterns: Cosmos would like to inform investors that it has recently received trading activity data from Shareholder Intelligence Services, LLC. Management is carefully reviewing the data in order to develop its next course of action.

https://finance.yahoo.com/news/cosmos-health-extends-updates-agreement-184000971.html

"What About The Sudden Deaths?": Pfizer CEO Confronted At Davos Over COVID-19 Vaccine

 While attention is now firmly shifting towards the scandalous Covid-19 vaccine rollout (and top-down censorship campaign), Pfizer CEO Albert Bourla has been largely insulated from criticism by legacy media outlets. Until now.

Canadian outlet Rebel News caught up with Bourla this week on the streets of Davos, where they peppered him with a list of uncomfortable questions.

As Rebel CEO Ezra Lavant writes:

You know, there are hundreds of “accredited” journalists here at the World Economic Forum — the biggest names in news, from CNN to the New York Times. But you have to understand: they’re all here as WEF members, not to hold the WEF to account. They’re on Pfizer’s team. They would never ask Pfizer a tough question.

I really don’t think their CEO knew what hit him today.

Watch: 

Here's a full list of questions asked via Rebel News:

• When did you know that the vaccines didn't stop transmission?

• How long did you know that without saying it publicly?

• Why did you keep it a secret that your vaccine did not stop transmission? 

• You said it was 100% effective then 90% and 80%, then 70% — but now we know that vaccines do not stop transmission. Why did you keep that a secret?

• Is it time to apologize to the world? To give refunds back to the countries that poured all their money into a vaccine that doesn't work?

• Are you ashamed of what you've done in the last couple of years?

• Are you proud of what you've done the past few years?

• You've made millions off the backs of people's livelihoods, how does it feel to walk the streets as a millionaire on the backs of the regular person at home in Australia, in England and Canada?

• What do you think about on your yacht? What do you think about on your private jet?

• Are you worried about product liability?

• Are you worried about myocarditis?

• What about the sudden deaths?

• What do you ahve to say about young men dropping dead from heart attacks every day?

• Why won't you answer these basic questions? No apology?

• Do you think you should be charged criminally for some of the behaviour you've been a part of?

• How much money have you personally made off the vaccine?

• How many boosters do you think it'll take for you to be happy enough with your earnings?

• Who did you meet with here in secret?

• Will you disclose who you met with?

• Who did you pay commissions to?

• In the past, Pfizer has paid $2.3 billion in fines for deceptive marketing. Have you engaged in that same conduct again?

• Are you under investigation, like you were before, for deceptive marketing?

• If any other product in the world doesn't work as promised, you get a refund. Should you not refund countries that pay billions for your ineffective vaccine?

• Are you only used to speaking to sympathetic media, is that why you don't know how to answer questions?

And of course, Bourla answered none of them.

https://www.zerohedge.com/covid-19/what-about-sudden-deaths-pfizer-ceo-confronted-davos-over-covid-19-vaccine

Zelensky secretly met with CIA Director Burns in Kyiv

 Ukrainian President Volodymyr Zelensky secretly met with CIA Director William Burns in Kyiv last week, several outlets reported on Thursday.

The two reportedly discussed the level of support that Ukraine can continue to expect from the U.S. with Republicans now in control of the House, according to The Washington Post, who first reported on the meeting.

House Republicans have suggested that they intend to rein in aid to Ukraine, but Burns assured Zelensky and his aides that President Biden remains steadfast in his support of the country.

The omnibus spending package that Congress passed in December also included about $45 billion in emergency funds for Ukraine, which they reportedly expect will last at least through July or August, the Post reported.

Burns has repeatedly briefed Zelensky throughout Ukraine’s nearly 11-month long war against Russia, according to The Associated Press.

Russia is largely expected to launch another major offensive in Ukraine this winter or early spring, following a series of losses on the battlefield last year.

https://thehill.com/policy/international/3820914-zelensky-secretly-met-with-cia-director-burns-in-kyiv/

Schiff introduce constitutional amendment to reverse Citizens United campaign finance ruling

 A group of House Democrats introduced a constitutional amendment on Thursday to overturn a Supreme Court ruling that eliminated restrictions on corporate campaign spending.

The Supreme Court’s 2010 ruling in the Citizens United v. FEC case prohibited the government from restricting political campaign spending by companies, nonprofit organizations and unions. This amendment, if passed, would allow Congress and state governments to enact “reasonable, viewpoint-neutral” limitations on campaign funding, including restricting corporations from spending “unlimited amounts of money to influence elections.”

Rep. Adam Schiff (D-Calif.), who introduced the amendment, said in a press release that it would “close legal loopholes” that corporations and other wealthy groups have “exploited for far too long.” Schiff has introduced an amendment to overturn the Citizens United ruling every year since 2013, according to the release.

“The flow of unrestricted corporate and dark money into our elections has dangerously eroded the American people’s faith in our democracy, and in our government’s ability to deliver for them and their families,” Schiff said in the statement. 

“Citizens United was one of the most egregious enablers of special interest money, but it was only the latest in a long line of Supreme Court cases that opened the floodgates. To truly rein in dark money, we must amend our Constitution,” he added.

The amendment, which was also introduced by Reps. Dean Phillips (D-Minn.), Pramila Jayapal (D-Wash.) and Jim McGovern (D-Mass.), would also allow states to set up public campaign financing systems that could restrict the influence of private wealth.

“We’ve introduced a constitutional amendment to overturn Citizens United and the irresponsible SCOTUS decisions that came before it,” Schiff said in a tweet announcing the amendment Thursday. “Unrestricted dark money has no place in our elections or democracy. We need to return power to people. Once and for all.”

The 2022 midterm election cycle was the most expensive in history, with outside donors spending more than $2 billion on federal midterm candidates, according to Open Secrets, a nonprofit organization that tracks money in politics.

https://thehill.com/homenews/house/3819814-democrats-introduce-constitutional-amendment-to-reverse-citizens-united-campaign-finance-ruling/

‘Concerning’ strain of gonorrhea detected in Massachusetts

 A novel strain of antibiotic-resistant gonorrhea has been identified in Massachusetts, health officials announced Thursday.

The strain was found to resist five classes of antibiotics, a first in the U.S., according to the Massachusetts Dept. of Public Health (DPH).

The two cases were ultimately cured with ceftriaxone, the lone remaining treatment recommended for gonorrhea. As of Thursday, officials said there was no known connection between the cases and that contact tracing was underway to see if there were any other infections.

Gonorrhea, a sexually transmitted disease (STD), can result in pelvic inflammatory disease, infertility, and other health problems if left untreated.

The novel strain has been seen in Asia-Pacific countries as well as the United Kingdom, but not in the U.S., according to the DPH. One case in Nevada had an infection that shared a genetic marker with the novel strain, but the disease proved sensitive to at least one class of antibiotics.

For years, experts have warned of the waning number of treatments for the sexually transmitted disease, which is one of the most common in the U.S. with an estimated 1.14 million infections annually, according to the Centers for Disease Control and Prevention (CDC).

Overall, these cases are an important reminder that strains of gonorrhea in the US are becoming less responsive to a limited arsenal of antibiotics,” the DPH said in a news release.

Healthcare providers were issued an alert to raise awareness of the new strain.

“The discovery of this strain of gonorrhea is a serious public health concern which DPH, the CDC, and other health departments have been vigilant about detecting in the US,” said Public Health Commissioner Margret Cooke. “We urge all sexually active people to be regularly tested for sexually transmitted infections and to consider reducing the number of their sexual partners and increasing their use of condoms when having sex. Clinicians are advised to review the clinical alert and assist with our expanded surveillance efforts.”

STD Surveillance Data (CDC)

Nationally, cases rose by 131% between 2009 and 2021, with 696,764 cases reported in the U.S. in 2021 according to preliminary data released by the CDC.

https://thehill.com/changing-america/well-being/prevention-cures/3820378-concerning-strain-of-gonorrhea-detected-in-massachusetts-officials-say/