ICER Suggests Benefits Of Lilly's Tirzepatide Not Better Than Other Diabetes Drugs

 nstitute for Clinical and Economic Review (ICER) casts doubts on Eli Lilly And Co’s 

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 (Get Free Alerts for LLY) tirzepatide, a type II diabetes candidate, about its usefulness to patients compared to the rivals.

• The ICER released its report, giving evidence for the drug a “B+” rating and saying, “the evidence provides high certainty that tirzepatide delivers at least a small net health benefit when added to background therapy, with the possibility of a substantial net health benefit.”
• However, ICER’s Jon Campbell, SVP for health economics, said that some uncertainty still exists.
• “When compared to injectable semaglutide in one head-to-head trial, tirzepatide showed a greater decrease in HbA1c levels, weight, triglycerides, and blood pressure,” Campbell said in a statement. “However, studies of cardiovascular outcomes with tirzepatide have not been concluded, and therefore there is still uncertainty on its true comparative clinical effectiveness about other available treatment options.”
• When ICER took a vote on clinical effectiveness, here’s what ended up happening:
• A unanimous majority (13-0) found the evidence for tirzepatide is enough to demonstrate a net health benefit when tirzepatide added to background therapy is compared to background therapy alone.
• A slight majority (7-6) found that the evidence is inadequate to demonstrate a net health benefit when tirzepatide added to background therapy is compared to injectable Novo Nordisk’s Ozempic (semaglutide). 
• A majority (10-2 with 1 abstention) found that the evidence is insufficient to demonstrate a net health benefit when tirzepatide added to background therapy is compared to Boehringer Ingelheim’s Jardiance (empagliflozin).
• The estimated annualized health benefit price benchmark range for tirzepatide is $5,500-$5,700 a year as per ICER. The Company predicted the drug price of around $4,643.50, based on injectable semaglutide.

https://www.benzinga.com/general/biotech/22/02/25667083/icers-report-suggests-benefits-of-eli-lillys-tirzepatide-not-better-than-other-diabetes-drugs

Merck Inks Oncology, Neurology Drug Pact With British Biotech, Curve Therapeutics

 Privately-held Curve Therapeutics has inked a contract with Merck & Co Inc 

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 (Get Free Alerts for MRK) to discover and validate modulators of up to five therapeutic targets using its Microcycle technology, initially for oncology and neurology indications.

• Under the agreement terms, Curve will receive an upfront payment and be eligible to receive research, development, and commercial milestones totaling up to $1.7 billion should all five therapeutic programs succeed. 
• Curve will also receive a royalty on net sales of any approved products resulting from the alliance.
• Curve will perform high throughput mammalian cell-based functional screening, hit characterization, data-mining and analysis, and Microcycle optimization. 
• Merck will be responsible for lead optimization, clinical development, manufacturing, and commercialization of compounds identified through the collaboration.
• Curve’s pipeline is led by drug candidates against hypoxia-inducible factor (HIF) and KRAS G12D. 

https://www.benzinga.com/general/biotech/22/02/25668417/merck-inks-oncology-neurology-drug-discovery-pact-with-british-biotech-curve-therapeutics

Wisconsin Senate Approves Protections for Unvaccinated

 The Republican-controlled Wisconsin Senate passed a package of bills Tuesday that push back against COVID-19 vaccine requirements and aim to shield workers who do not want to protect themselves from the virus by being inoculated.

Senators approved the bills in the wake of protests in Canada over vaccine requirements. Those protests blocked the busiest U.S.-Canada border crossing. Wisconsin has no statewide vaccine or mask mandates.

There have been moves in other states and cities to require vaccinations for workers.

All four of the Wisconsin bills are almost certain to be vetoed by Democratic Gov. Tony Evers, who is a strong supporter of vaccinations as one of the best ways to curb the spread of the virus that has killed more than 11,000 people in Wisconsin over the past two years.

An Evers spokeswoman did not immediately return a message seeking comment.

Republicans who introduced the proposals say they are responding to voters who have contacted them, fearful of losing their jobs if they don't get the vaccine.

One measure would require employers to count a prior coronavirus infection as an alternative to vaccination and testing. Another would ban so-called vaccine passports and prohibit businesses, colleges and universities, governments and anyone else in the state from requiring proof of COVID-19 vaccination.

Supporters of banning vaccine passports have likened requiring people to show proof of vaccination to Cold War-era Russia and Nazi Germany.

Opponents, including leaders of the state's medical community, say vaccine requirements at hospitals and other health care facilities help ensure that patients and workers in health care settings do not get sick.

Medical groups opposed to the natural immunity bill say that vaccination is the best way to protect against COVID-19 and that it's not clear how long immunity lasts after an infection. Similar bills passed in Florida and Arkansas last year.

According to data from the Wisconsin health department, unvaccinated people are hospitalized at a rate nearly 10 times higher than fully vaccinated people and are 14-times more likely to die.

Democratic Sen. Chris Larson, of Milwaukee, said it may be good politics to fight COVID-19 restrictions, but it's putting people's lives at risk and slowing recovery from the pandemic. He accused Republicans of "coddling the extremists who are refusing to do their part."

"The rest of us, the majority of Wisconsinites who have gotten vaccinated, the majority of the country who wants to get on with our lives would like you guys to move on so we can open up again," Larson said.

Republican Sen. Mary Felzkowski, sponsor of the natural immunity bill, said she had COVID-19 twice and both she and her husband took the anti-work drug ivermectin. She said it was prescribed to her, though health officials have warned that it shouldn't be used to treat COVID-19.

She said forcing people to be vaccinated was un-American.

"This is a vote very much based on science and recognizing the God-given ability to fight off infections that our creator gave us," she said.

The Republican-controlled Assembly previously passed both of those bills. Senate approval sends them to Evers. Last year, Evers vetoed a GOP bill that would have barred public health officials from requiring people get vaccinated.

The Senate also passed a pair or other Republican-introduced measures that have yet to get a vote in the Legislature.

One says that people who quit or fired from a job after refusing to get vaccinated can still qualify for state unemployment benefits. Under current law, employees who quit generally aren't eligible for unemployment payments. The bill also says that refusing to be vaccinated does not constitute misconduct or substantial fault, which are both reasons that a person could be refused unemployment benefits.

The other bill says that anyone who is injured due to receiving a COVID-19 vaccine his employer required would be eligible for workers' compensation.

Vaccine Choice Wisconsin, a group opposed to vaccine mandates, was the only organization that registered in support of all four bills. Opponents of one or more of them include the Wisconsin Medical Society, the Wisconsin Public Health Association and the Medical College of Wisconsin.

All four of the bills passed on party line votes, with Republicans in support and Democrats opposed.

https://www.medscape.com/viewarticle/968630

37% of COVID Patients Lose Sense of Taste: Study

 About four in 10 COVID patients have some sort of taste loss, according to a new study.

Many COVID-19 patients report losing their sense of taste as well as their sense of smell, but scientists have been skeptical because the two senses are closely related and it was relatively rare for people to lose their taste sense before the COVID pandemic, says the Monell Chemical Senses Center, a nonprofit research institute in Philadelphia.

But a new Monell Center analysis found that 37% -- or about four in every 10 -- of COVID-19 patients actually did lose their sense of taste and that "reports of taste loss are in fact genuine and distinguishable from smell loss."

Taste dysfunction can be total taste loss, partial taste loss, and taste distortion. It's an "underrated" symptom that could help doctors better treat COVID patients, the Monell Center said in a news release.

"It is time to turn to the tongue" to learn why taste is affected and to start on how to reverse or repair the loss, said Mackenzie Hannum, PhD, an author of the report and a postdoctoral fellow in the lab of Danielle Reed, PhD.

Researchers looked at data about 138,785 COVID patients from 241 studies that assessed taste loss and were published between May 15, 2020, and June 1, 2021. Of those patients, 32,918 said they had some form of taste loss. Further, female patients were more likely than males to lose their sense of taste, and people 36-50 years old had the highest rate of taste loss.

The information came from self-reports and direct reports.

"Self-reports are more subjective and can be in the form of questionnaires, interviews, health records, for example," Hannum said. "On the other hand, direct measures of taste are more objective. They are conducted using testing kits that contain various sweet, salty, and sometimes bitter and sour solutions given to participants via drops, strips, or sprays."

Though self-reports were subjective, they proved just as good as direct reports at detecting taste loss, the study said.

"Here self-reports are backed up by direct measures, proving that loss of taste is a real, distinct symptom of COVID-19 that is not to be confused with smell loss," said study co-author Vicente Ramirez, a visiting scientist at Monell and a doctoral student at the University of California, Merced.

Source

Monell Center: "Monell Center Researchers Estimate the True Prevalence of COVID-19 Taste Loss."

https://www.medscape.com/viewarticle/968641

Pfizer waits for paediatric Comirnaty data to mature

 Pfizer’s golden touch when it comes to vaccines and treatments for Covid unexpectedly failed this week. The company and its partner Biontech are to hand the FDA more data on their vaccine Comirnaty in young children, likely setting back authorisation for this use by at least two months.

Better regulatory news came for Lilly, whose therapy bebtelovimab was authorised by the FDA for certain patients with mild-to-moderate Covid. And, on the clinical side, mixed data on Glaxosmithkline’s authorised antibody Xevudy raise questions about its effectiveness against the new subvariant of Omicron.

Vaccines

The phase 1/2/3 paediatric study of Comirnaty has enrolled three age groups: six months to one year; two to four years; and five to 12 years. In December Pfizer and Biontech decided to administer a third 3μg shot to the first two cohorts after the two-jab regimen yielded disappointing efficacy. They are now waiting for the third-dose data to come in before adding it to their rolling submission in this age group, which was begun on February 1.

This has prompted the FDA to delay the adcom assessing the vaccine in patients aged six months to four years. Originally scheduled for yesterday, the panel, had it been positive, could have permitted launch in the 18 million or so US children in this bracket. No new panel date has been set, though Pfizer and Biontech reckon they can get the three-dose data to the agency by early April. 

Novavax, meanwhile, trumpeted positive data on its vaccine, Nuvaxovid, in a slightly older population. In the paediatric expansion of its pivotal Prevent-19 trial, the jab showed 79.5% efficacy among patients aged 12 to 17, at a time when the Delta variant was predominant. Vaccine efficacy in cases confirmed to be Delta was 82.0%.

Though Nuvaxovid is not yet authorised even for adults in the US, Novavax plans to file for authorisation in 12 to 17-year-olds this quarter, and to begin studies in younger patients during the second quarter.

In the future, protection against Covid might not be a matter of jabs at all. Covigen, a DNA-based vaccine administered using a needle-free device, has been given a clean bill on safety in a phase 1 trial. The study will go on to report immunogenicity data on Covigen, which was developed by the Australian biotech Technovalia and drug delivery group Pharmajet. 

Pharmajet’s delivery technology is also used with ZyCoV-D, the world’s first DNA-based Covid vaccine, which last year gained emergency authorisation in India. But DNA vaccines for the coronavirus are far from proven, and the history of needle-free vaccine development has been beset by failure. Covigen will have to post outrageously good results in much bigger trials to be regarded as a real contender. 

Antibodies

Not all the Covid action is related to vaccines. Several developers of therapies have seen intriguing developments over the past week or so. 

Chief among these is Lilly and Abcellera, whose bebtelovimab has gained US authorisation, albeit in a smallish niche. The MAb may be given to patients aged 12 and up with mild-to-moderate Covid who are at high risk for progression to severe disease, including hospitalisation or death, and for whom other authorised treatments are inaccessible or inappropriate. It is not authorised for patients already in hospital. 

The move ought to make up for the fact that the partners’ antibody combo bamlanivimab plus etesevimab is ineffective against Omicron. Crucially, lab testing has shown that bebtelovimab retains activity against both Omicron and the BA.2 subvariant.

It is exactly this question that is exercising followers of Glaxosmithkline and its partner Vir Biotechnology. Xevudy (sotrovimab) also has activity against Omicron, but contradictory data have emerged on whether it is active against BA.2. According to Vir the MAb is effective, and a preprint showing this is imminent. 

But a preprint that has already appeared seems to show the opposite. Compared with a wild-type pseudovirus, Xevudy neutralising activity against Omicron dropped sevenfold, which according to the authors means that it retained appreciable activity against the variant. When it came to the BA.2 subvariant, however, Xevudy lost 27-fold neutralising activity versus wild-type. 

The same preprint included data on bebtelovimab, confirming its efficacy against both Omicron and BA.2. 

Fold change in IC50 relative to wild-type
Variant	Sotrovimab (Xevudy, Glaxo/Vir)	Bebtelovimab (Lilly/Abcellera)
Omicron	-6.9	1.4
Omicron subvariant BA.2	-27.0	1.1
Source: adapted from preprint.

All this is based on in vitro testing, however, and has yet to undergo peer review, so it would be unwise to draw sweeping conclusions at this stage. 

Lack of efficacy might also come to be the Achilles heel of Merck & Co and Ridgeback’s antiviral molnupiravir – though not against Omicron or its subvariants so much as the virus in general. According to the Financial Times the pill might be denied EU authorisation owing to lacklustre performance in its pivotal trial. 

Though molnu remains on the market in the US and the UK, it is generally the third choice following Pfizer’s Paxlovid, whose efficacy sits at 89%, and Xevudy. 

https://www.evaluate.com/vantage/articles/news/policy-and-regulation/pfizer-waits-paediatric-comirnaty-data-mature

Mirati and the elephant in the room

 The sellside’s support for Mirati in the wake of the group’s latest delay for adagrasib is admirable, but it ignores one very large problem. To wit: after a standard 10-month review, Mirati will be seeking accelerated approval for adagrasib – on the surrogate endpoint of remission rates – at a time when Amgen’s rival Lumakras will have yielded confirmatory survival data. At worst Lumakras might already have secured full approval by this point, destroying the basis for an accelerated adagrasib approval. After already losing 12 months to Amgen Mirati had been hoping for a priority six-month review, and investors can ignore the new risk at their peril. Yesterday Stifel said drugs could still be greenlit before their Pdufa dates; Leerink called the FDA’s decision to hold Mirati to standard review “perplexing”, and even suggested the agency’s Covid-related backlog as a reason. This overlooks the fact that in the middle of the pandemic Lumakras’s filing had been turned around in just three months, and that last year Agenus had to pull an accelerated filing once Merck & Co secured full approval for a similar drug in a similar indication. With Lumakras already available the FDA might simply not consider adagrasib a priority.

Timeline of the duelling Kras G12C inhibitors in lung cancer
	Lumakras (Amgen)	Adagrasib (Mirati)
Accelerated filing for 2L Kras G12C+ve NSCLC accepted	16 Feb 2021	15 Feb 2022
Goal action date	16 Aug 2021 (priority review)	14 Dec 2022 (standard review)
Accelerated US approval	28 May 2021	Late 2022*
Confirmatory study readout	H2 2022 (Codebreak-200)	H2 2023 (Krystal-12)
Full US approval	Possible in H2 2022	2023/24
Note: *assumes that this option remains open; if not the FDA will likely wait until confirmatory survival data from Krystal-12. Source: company statements. https://www.evaluate.com/vantage/articles/news/policy-and-regulation-snippets/mirati-and-elephant-room

New Data Back Efficacy of Gilead HIV-1 Capsid Inhibitor

 One-Year Data From the CAPELLA and CALIBRATE Trials Show Lenacapavir Leads to High Rates of Virologic Suppression in Heavily Treatment-Experienced People Living with Multi-Drug Resistant HIV and Treatment-Naïve People Living with HIV –

Gilead Sciences, Inc. (Nasdaq: GILD) today announced new one-year results from the ongoing Phase 2/3 CAPELLA trial evaluating lenacapavir, the company’s investigational, long-acting HIV-1 capsid inhibitor, in heavily treatment-experienced people living with multi-drug resistant HIV. The findings demonstrated that lenacapavir, administered subcutaneously every six months in combination with other antiretrovirals, achieved high rates of virologic suppression and clinically meaningful increases in CD4 counts in people living with HIV whose virus was no longer effectively responding to their current therapy. In this patient population with high unmet medical need, 83% (n=30/36) of participants receiving lenacapavir in combination with an optimized background regimen achieved an undetectable viral load (<50 copies/mL) at Week 52. The data were presented at the 29th Conference on Retroviruses and Opportunistic Infections (virtual CROI 2022).

https://finance.yahoo.com/news/clinical-data-support-sustained-efficacy-185500212.html