Key Nov FDA Decisions

 Food and Drug Administration decisions and advisory committee verdicts slated for November were mostly positive. New molecular entity approvals so far this year trail 2021’s tally by about 35%.

The two NMEs that were okayed in November include Provention Bio, Inc.’s 

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 Tzield, approved for delaying the onset of stage-3, type-1 diabetes, and ImmunoGen Inc.’s 

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 mirvetuximab soravtansine monotherapy – a treatment for recurrent ovarian cancer resistant to platinum therapy.

On the flip side, Spectrum Pharmaceuticals, Inc. 

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 received a complete response letter for its lung cancer drug application, prompting the company to pull the plug on the program.

Benzinga has previewed December’s Prescription Drug User Fee Act dates — deadlines fixed by the FDA to communicate its decision about the approval or non-approval of a drug.

It is a binary catalyst that can trigger big swings in stocks.

Can Mirati Get The Nod To Play Catch-Up To Amgen?

Company:  Mirati Therapeutics Inc. 

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Type of Application:  New drug application

Candidate:  adagrasib

Indication:  lung cancer

Date:  Dec. 14

Mirati’s adagrasib NDA was accepted for review in mid-February as a treatment option for patients with non-small cell lung cancer harboring KRAS G12C mutation, who have received at least one prior systemic therapy. If approved, adagrasib will be pitched against Amgen Inc.’s 

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 Lumakras – also a KRAS G12C inhibitor that was approved by the FDA in May 2021.

Lumakras fetched Amgen $214 million in revenue for the first three quarters of 2022.

Adagrasib’s uptake will largely hinge on the differences in its labeling vis-à-vis Amgen’s. Mirati currently has an out-licensing partnership with Chinese biotech Zai Labs Limited 

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 for marketing the investigational drug in Greater China. FDA's decision on the drug, therefore, will likely have an impact on Zai Lab’s stock too.

Can 2nd Time Be Charm For Coherus?

Company:  Coherus Biosciences, Inc. 

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Type of Application:  biologic license application

Candidate:  toripalimab

Indication:  nasopharyngeal carcinoma

Date:  Dec. 23

Coherus and Chinese partner Shanghai Junshi Biosciences faced a rejection in May when the FDA issued a complete response letter for its toripalimab BLA. Toripalimab has been evaluated in combination with chemotherapy medications gemcitabine and cisplatin for the first-line treatment of patients with advanced recurrent or metastatic nasopharyngeal carcinoma.

It is also being studied as a monotherapy in second-line or later treatment of recurrent nasopharyngeal carcinoma after platinum-containing chemotherapy.

As the complete response letter sought only a quality process change, the companies resubmitted the BLA shortly after. The FDA accepted the resubmitted application in early July.

”Go” or No-Go” For Gilead’s Long-Acting AIDS Drug On Second Try?

Company:  Gilead Sciences, Inc. (NASDAQ: GILD_

Type of Application:  NDA

Candidate:  lenacapavir

Indication:  HIV-1 infection

Date:  Dec. 27

Gilead’s lenacapavir is a long-acting HIV-1 capsid inhibitor for the treatment of HIV-1 infection in heavily treated people with multi-drug resistant HIV-1 infection. The original regulatory application was shot down with a complete response letter in March due to concerns over chemistry, manufacturing and controls issues.

The company’s resubmission was accepted for review in late July.

In late August, the European Commission approved the drug with the brand name Sunlenca. The company touts lenacapavir as a new, every-six-month treatment option that can be apt for HIV patients whose virus no longer effectively responds to their current therapy.

TG Therapeutics MS Therapy Awaits FDA Nod

Company:  TG Therapeutics, Inc. 

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Type of Application:  BLA

Candidate:  ublituximab

Indication:  relapsing multiple sclerosis

Date:  Dec. 28

TG Therapeutics’ublituximab review period was extended by three months in May, with the new PDUFA date set for Dec. 28. Ublituximab is an investigational monoclonal antibody that targets a unique epitope on CD20-expressing B-cells. It is being evaluated for relapsing multiple sclerosis, a chronic disease of the central nervous system.

If approved, ublituximab will be up against Roche Holding AG’s 

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 Ocrevus and Novartis AG’s 

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 Kesimpta.

Adcom Meetings 

FDA’s Cardiovascular and Renal Drugs Advisory Committee is scheduled to meet on Dec. 13 to discuss Cytokinetics, Inc.’s 

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 NDA for omecamtiv mecarbil tablets. This investigational drug is being evaluated for reducing the risk of cardiovascular death and heart failure events in patients with symptomatic chronic heart failure with reduced ejection fraction.

https://www.benzinga.com/general/biotech/22/12/29930148/mirati-plays-catch-up-with-amgen-gileads-2nd-try-with-aids-drug-cytokinetics-adcom-test-and-more-

Three Arrows Capital Liquidators Seek $30 M From Sale Of "Much Wow" Superyacht

 The crypto industry continues to "pick up the pieces" after its epic collapse over the last 6 months, culminating in the implosion of FTX last month.

Three Arrows Capital, another firm that went under due to the plunging price of bitcoin, is in the process of being liquidated. Those in charge of dispersing of its assets are now looking to raise $30 million from the sale of a superyacht called "Much Wow".

We first wrote that the yacht was being considered for sale in the bankruptcy this summer.

On Friday, a filing in the U.S. Bankruptcy Court in the Southern District of New York by the company's liquidator, Teneo, confirmed that it had recovered $35.6 million in cash, $2.8 million from forced redemptions and "over 60" different crypto tokens and NFTs, Coingape reported.

Teneo is also seeking $30 million from the sale of the yacht, which is said to be worth $50 million. According to the report, founders of 3AC used company funds to purchase the yacht, but never made its final payment. 

The yacht is currently "in insolvency proceedings in the Cayman Islands", the report says. 

Company founder Kyle Davies recently "criticized liquidators for refusing to engage with them constructively," the report continues. Teneo has spoken out and said that they Davies and founder Zhu Su are delaying the return of funds to creditors. 

The founders are in Bali and Dubai, respectively, and their U.S. citizenship is "unclear", making it difficult to subpoena them. 

https://www.zerohedge.com/markets/three-arrows-capital-liquidators-seek-30-million-sale-much-wow-superyacht

Pentagon chief calls on Congress to pass spending bill on time

 Like Captain Renault in the gambling casino in “Casablanca,” congressmen are “shocked, shocked” by all the fraud spawned by the trillions of dollars in COVID handouts they approved.

The House Select Subcommittee on the Coronavirus Crisis issued a report Thursday blaming fintech firms for the pilfering of Paycheck Protection Program loans that began in 2020. But the real fraud is the illusion that members of Congress give a damn about plundering American taxpayers.

PPP was enacted in March 2020 and eventually provided $800 billion in loans to more than 11 million businesses. Congress designed the program to carpet-bomb the nation with federal tax dollars.

The Small Business Administration, which administered the plan, effectively told people, “Apply and sign and tell us that you’re really entitled to the money,” said Justice Department Inspector General Michael Horowitz. He testified PPP was an invitation to fraudsters because there weren’t “even minimal checks to make sure that the money was getting to the right people at the right time.”

Government investigators estimate up to $100 billion in PPP loans was fraudulent. The feds gave 342 people who said their name was “N/A” PPP loans. Dozens of New York City and New York state employees were arrested this week for their role in a multimillion-dollar PPP fraud scheme.

After 15 Illinois jailbirds used PPP loans to pay their bail, cynics scoffed that the program should be named the Prisoner Paycheck Program. In Florida, a PPP loan was used to bankroll a murder-for-hire plot that left a Transportation Security Administration agent dead.

Happily, a scapegoat has been found. According to the new congressional report, the problem was that the financial-technology companies (fintechs) that handled PPP-claims applications failed to show due diligence. Rep. Jim Clyburn (D-SC), the select subcommittee’s chairman, declared that “many fintechs … refused to take adequate steps to detect and prevent fraud despite their clear responsibility to safeguard taxpayer funds.”

PPPs were a typical legislative monstrosity where the profits were privatized while taxpayers suffered the losses. Some fintechs shamelessly exploited a reckless program and received hefty fees based on the loans they approved.

• Kabbage, Inc.’s policy chief scoffed in a September 2020 email: “At the end of the day, it’s the SBA’s s—ty rules that created fraud, not” us.

• “Womply’s CEO — who was convicted of insider trading in 2014 and has been permanently barred from participating in the securities industry — led Womply’s fraud prevention efforts and instructed his company to not cooperate with federal PPP fraud investigators,” the report charged.

Rep. Clyburn declared, “We must learn from this inexcusable misconduct to erect guardrails that will help ensure that federal programs” are better administered in the future. But it was Congress that inexcusably failed to include any PPP guardrails when it catapulted hundreds of billions at the program.

Almost all the PPP loans have been “forgiven” because employers claimed to have kept employees on their payroll — often despite indicators of fraud that the feds are too busy to pursue.

Rep. James Clyburn said the tech firms “refused to take adequate steps to detect and prevent fraud.”

AP Photo/J. Scott Applewhite

Though Clyburn now claims to be aghast at the wasteful spending, he championed the political exploitation of the COVID pandemic when Congress created PPP. “This is a tremendous opportunity to restructure things to fit our vision,” he proclaimed in a March 2020 closed phone call with other House Democrats.

Democrats milked the COVID bill to seek changes for the 2020 election (including “no-excuse absentee voting and vote-by-mail,” as Clyburn bragged), medical subsidies and college funding. Citizens Against Government Waste designated Clyburn the Porker of the Month for “trying to take advantage of the coronavirus crisis to promote a radical agenda.”

The select subcommittee sifted through 83,000 pages of internal documents from private companies to compile its 120-page report. But it would be far more interesting to see a report excerpted from tens of thousands of PPP-related emails, texts and letters from members of Congress, their staff and their campaign operations.

When did our “best and brightest” recognize PPP would be the biggest boondoggle of the century? Did they take any steps to fix the problem or curb the looting? (Did hell freeze over?) How many members of Congress sought campaign contributions as a result of the geyser of COVID spending they unleashed?

Don’t expect to see any such report ever come from Capitol Hill. Squandering a hundred billion tax dollars is simply another congressional office perk. Politicians don’t give a damn about any government waste that buys them applause, votes or campaign contributions.

James Bovard is the author of 10 books and a member of the USA Today Board of Contributors.

https://nypost.com/2022/12/01/congress-is-shocked-shocked-by-the-covid-fraud-it-created/

Pentagon chief calls on Congress to pass spending bill on time

 

U.S. Defense Secretary Lloyd Austin on Saturday called on Congress not to delay in passing the full-year Pentagon spending bill, known as an omnibus, saying it was key to helping keep America secure.

"Let me urge Congress to pass an on-time appropriation so that we can get the capabilities to further strengthen our deterrence," Austin told the Reagan National Defense Forum in Simi Valley, California, which was attended by Republican and Democratic lawmakers.

A commonly floated alternative to an omnibus, known as a continuing resolution, or CR, would effectively freeze spending at current levels. Such a bill would require the armed forces to rely on legacy equipment, while development of new military technologies would largely cease, U.S. lawmakers have warned.

https://www.marketscreener.com/news/latest/Pentagon-chief-calls-on-Congress-to-pass-spending-bill-on-time--42472997/

'Putin not sincere about peace talks now': Nuland in Ukraine

 

Russian President Vladimir Putin is not sincere about peace talks with Ukraine at this time, a top U.S. diplomat said on Saturday after meeting President Volodymyr Zelenskiy and other senior Ukrainian officials in Kyiv.

U.S. Under Secretary for Political Affairs Victoria Nuland visited Ukraine to show support at a time when Russia is trying to destroy the country's energy infrastructure.

"Diplomacy is obviously everyone's objective but you have to have a willing partner," she told reporters.

"And it's very clear, whether it's the energy attacks, whether it's the rhetoric out of the Kremlin and the general attitude, that Putin is not sincere or ready for that."

U.S. President Joe Biden said on Thursday he was prepared to speak to Putin if the Russian leader was interested in ending the war. But the idea died quickly when the Kremlin said the West must recognize Moscow's declared annexation of four Ukrainian regions.

This reaction from Russia, Nuland said, showed "how not serious they are".

Nuland also met Andriy Yermak, the head of Zelenskiy's office, who expressed thanks for the billions of dollars worth of aid Washington has committed to Ukraine.

"Ukraine's victory, which we are sure of, will be our joint victory," Zelenskiy's office quoted him as telling Nuland.

https://www.marketscreener.com/quote/currency/US-DOLLAR-RUSSIAN-ROUBL-2370597/news/Putin-not-sincere-about-peace-talks-now-says-top-U-S-diplomat-42472986/

High Drug Costs Exclude Most Neurology Patients From Cutting-Edge Treatment

 Because of high out-of-pocket costs of new-to-market neurologic drugs that are of similar benefit as older agents, only a small percentage of patients with neurologic disorders have access to these cutting-edge medications, new research shows.

"Our study of people with neurologic conditions found fewer than 20% were being treated with new medications," study author Brian C. Callaghan, MD, with University of Michigan Health in Ann Arbor, said in a statement.

"For new, high-cost medications that have similar effectiveness to older drugs, limited use is likely appropriate. However, future studies are needed to look into whether the high costs are barriers to those new medications that can really make a difference for people living with neurologic disease," Callaghan said.

The study was published online November 30 in Neurology.

Most Expensive Drugs

Using insurance claims data, the investigators compared the utilization and costs of new-to-market drugs from 2014 to 2018 to those for existing guideline-supported medications for treating 11 neurologic conditions.

The new drugs included erenumab, fremanezumab, and galcanezumab for migraine; ocrelizumab and peginterferon beta-1a for multiple sclerosis (MS); pimavanserin and safinamide for Parkinson's disease; droxidopa for orthostatic hypertension; eculizumab for myasthenia gravis (MG); edaravone for amyotrophic lateral sclerosis (ALS), deutetrabenazine and valbenazine for Huntington disease and tardive dyskinesia; patisiran and inotersen for transthyretin amyloidosis (ATTR), eteplirsen and deflazacort for Duchenne disease, and nusinersen for spinal muscular atrophy (SMA).

Utilization of new drugs was modest ― they accounted for 1 in 5 prescriptions for every condition except tardive dyskinesia (32% for valbenazine), the researchers note.

Mean out-of-pocket costs were significantly higher for the new medications, although there was large variability among individual drugs.

The two most expensive drugs were edaravone, for ALS, with a mean out-of-pocket cost of $713 for a 30-day supply, and eculizumab, for MG, which costs $91 per month.

"For new-to-market medications, the distribution of out-of-pocket costs were highly variable and the trends over time were unpredictable compared to existing guideline-supported medications," the authors report.

They note that potential reasons for low utilization of newer agents include delay in provider uptake and prescriber and/or patient avoidance because of high cost.

Given that most of the new neurologic agents offer little advantage compared to existing treatments ― exceptions being new drugs for SMA and ATTR ― drug costs should be a key consideration in prescribing decisions, Callaghan and colleagues conclude.

One limitation of the study is that follow-up time was short for some of the recently approved medications. Another limitation is that the number of people in the study who had rare diseases was small.

Revolution in Neurotherapeutics

"We are living in a time when new treatments bring hope to people with neurologic diseases and disorders," Orly Avitzur, MD, president of the American Academy of Neurology, said in a statement.

"However, even existing prescription medication can be expensive and drug prices continue to rise. In order for neurologists to provide people with the highest quality care, it is imperative that new drugs are accessible and affordable to the people who need them," Avitzur added.

Writing in a linked editorial, A. Gordon Smith, MD, professor and chair, Department of Neurology, Virginia Commonwealth University, Richmond, said there is a revolution in neurotherapeutics, with particularly robust growth in new drug approvals for orphan diseases (those affecting <200,000 Americans).

"This study adds to a growing literature indicating rising drug prices are a threat to the health care system. No matter how effective a disease modifying therapy may be, if a patient cannot afford the cost, it doesnt work," Smith writes.

He added that neurologists must be "diligent in assessing for financial toxicity and appropriately tailor individual treatment recommendations. We must insist on development of point of care tools to accurately estimate each patients potential financial toxicity including RTBT [real-time benefit tools].

"Neurologists' primary obligation is to the individual patient, but we are also compelled to support access to high quality care for all people, which requires advocacy for appropriate policy reforms to ensure value based and fair drug pricing and treatment success," Smith adds.

The study was funded by the American Academy of Neurology Health Services Research Subcommittee. Callaghan consults for a PCORI grant, DynaMed, receives research support from the American Academy of Neurology, and performs medical/legal consultations, including consultations for the Vaccine Injury Compensation Program. Smith has disclosed no relevant financial relationships.

Neurology. Published online November 30, 2022. Abstract, Editorial

https://www.medscape.com/viewarticle/984953

TikTok Trend That Triggered a Diabetes Drug Shortage

 Weight loss advice is everywhere you look on social media, but one trend sweeping TikTok has led to shortages of an important diabetes drug. 

Ozempic, a weekly injection that helps boost insulin sensitivity in people with type 2 diabetes, also suppresses appetite, which leads to weight loss. Stories of celebrities using the drug off-label to lose a few pounds have led to an explosion of interest. And now people with diabetes – people whose lives could be saved by the drug – are having trouble finding it.

Kim Kardashian and Elon Musk

In the spring, Kim Kardashian pulled off a dramatic weight loss to fit into Marilyn Monroe’s dress for the Met Gala. Soon rumors began to circulate that she’d used Ozempic to do it. Just this week, new Twitter owner Elon Musk tweeted about his own use of Ozempic and its sibling drug, Wegovy.

Variety dubbed Ozempic “the worst kept secret in Hollywood – especially given that its most enthusiastic users are not pre-diabetic and do not require the drug.” The rich and famous are spending $1,200 to $1,500 a month to get access.

As so often happens, high-profile use sparked a trend. Videos on TikTok hashtagged #ozempic have amassed more than 275 million views, and #ozempicweightloss has more than 110 million.

This raises concerns about who, exactly, is watching these videos, and what message they’re receiving.

“Forty-two percent of Americans have obesity, and even more have overweight. That’s affecting our younger people and our adolescents,” says Caroline Apovian, MD, co-director of the Center for Weight Management and Wellness at the Brigham and Women's Hospital in Boston. “They’re looking at TikTok and other social media outlets for help.”

A new study shows how damaging this can be: Researchers analyzed 1,000 videos with nutrition, food, and weight-related hashtags, with over 1 billion views combined. They found that nearly all included messages glorifying weight loss and thinness.

At Last, an Effective Weight Loss Drug

Ozempic is Danish drug company Novo Nordisk’s brand name for semaglutide, which works by mimicking a naturally occurring hormone known as GLP-1. It travels to your brain and helps you feel full on less food. That leads to weight loss. In one 68-week study, semaglutide helped people lose an average of 15% of their body weight. But it’s not a miracle drug: You still have to change your eating habits and stay physically active.

The FDA approved Ozempic to treat people with type 2 diabetes in 2017. Four years later, Novo Nordisk received the green light for a higher-dose version meant specifically for people with obesity. Wegovy is approved for use only if you have a BMI of at least 27 with one or more weight-related ailments, or a BMI of 30 or more with none.

“These drugs are dominating my practice, because they’re so effective,” says Amanda Velazquez, MD, director of obesity medicine at Cedars-Sinai Medical Center in Los Angeles. The drug is considered safe, “so the majority of patients are good candidates.”

More Demand Than Supply

As word spread about how well Ozempic and Wegovy worked, social media posts helped drive even more people to seek out the drugs. Now demand is outpacing the supply – according to the FDA, starter doses of Ozempic will have limited availability through January. 

“In Hollywood, people are losing 10 pounds, getting it for $1,500 a month, and depleting stores for people who have such severe obesity that they have congestive heart failure and diabetes,” Apovian says. “These are people who are going to die, and you're taking it away just for cosmetic weight loss. That is deplorable.”

In addition to huge demand, Wegovy also had a disruption in its supply chain. Right now, it isn’t available at all in lower doses, which is helping to spike off-label demand for Ozempic. Novo Nordisk expects to have these problems sorted out by the end of the year, with distribution following soon after.

The Price of Access

With a list price of $1,350 a month, Wegovy costs as much as many mortgages. And Medicaid, Medicare, and many insurance companies don’t cover it. Although obesity is a disease, the insurance industry treats weight loss as more of a vanity issue – so even if you could find the drug, you might not be able to afford it. 

“We’re seeing that roughly half the prescriptions we write aren’t being covered,” Apovian says. “And for the half that are covered, we have to do prior authorization, which takes days, and it’s laborious.” In some instances, she says, insurance companies withdraw authorization after 3 months if they don’t see enough weight coming off.

It’s not like you can take Wegovy for 3 months, lose some weight, and expect it to stay off, either. The medication requires a real commitment, potentially for life. That’s because once the semaglutide leaves your system, your appetite returns. In one study, people regained two-thirds of the weight they’d lost within a year of stopping.

Many see a double standard in the insurance companies’ refusal to cover a drug that could prevent serious illness or death. 

“They’re saying it’s not cost-effective to give the 42% of Americans who have a BMI over 30 Wegovy. Did they say this when statins came out?” Apovian says. “Why are they doing this with antiobesity agents? It’s the culture. The culture isn’t ready to adopt obesity as the disease that it is.”

Unpleasant Side Effects

Let’s assume you’re one of the lucky ones – your insurance covers Wegovy, and you can actually find some. You might discover that using it is no walk in the park. Common side effects include gastrointestinal issues like nausea, vomiting, and diarrhea. 

“The way we counteract that is to start very slowly at a low dose of these medications,” Apovian says. “We only go up when the patient doesn’t have nausea or it gets better.”

Elise Davenport was excited to try Wegovy. “I did my online research. I’m the type who’s interested in early adoption, tech gadgets and stuff,” says the 40-year-old technical writer. “I wanted to try it because I’d tried so many other things that failed, or hadn’t worked long-term.”

With a BMI over 30, Davenport qualified for the drug. She signed up for an online program that guaranteed insurance coverage and started taking it in October 2021. At first, the side effects were mild, just a touch of nausea and diarrhea. And the results were impressive. She found it easy to feel satisfied with smaller portions and lost her cravings for sugar and highly processed foods. The weight fell off, roughly 5 pounds a week. 

It turns out, that’s too much, too fast. Apovian and Velazquez say their patients lose more like 2 pounds each week, with careful monitoring. 

By early December, Davenport’s side effects were ramping up. Because of shortages in lower dosages, the online program wasn’t able to adjust hers right away. She felt nauseated all the time, bad enough that brushing her teeth made her vomit and she had to force herself to eat. Some weeks, she managed less than 500 calories a day. Her sleep patterns became erratic. And then her depression, which medication had kept under control for years, spiraled.

“I remember sitting on the floor of my bathroom crying, thinking I’d rather carry the extra weight,” she says. “I used to take a lot of enjoyment from food, and I had none of that anymore. It was such a joyless experience at that point.” 

Eventually, her dosage was reduced and the symptoms let up, but her primary care doctor encouraged her to stop. By the time she did, in March, she’d lost 55 pounds. So far, she’s gained back about 10.

More Than Just Weight Loss

Even though Davenport’s experience wasn’t a good one, with better monitoring, she’d be willing to try again. For one thing, seeing how easy it was to eat less with medical help helped to undo years of shame.

“Our culture treats obesity like a moral failing. I realized I’d been made to feel that way by doctors and programs – that I wasn’t doing enough,” she says. “This drug made me realize there are legit physiological things going on in my body, things that are often excluded from the conversation.”

Apovian and Velazquez say their patients regularly discover similar things.

“Obesity is not a disease of willpower. Medications are not the easy way out,” Velazquez says. “This is a chronic, relapsing medical condition, and because of that, we should treat it how we treat diabetes, high blood pressure, all these other conditions. We’d never hold back medication for individuals coming in with high blood pressure, tell them to work on willpower and withhold drugs they’d qualify for.”

https://www.medscape.com/viewarticle/984758