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Wednesday, December 1, 2021

Amgen: FDA Approves Kyprolis Combination to Treat Multiple Myeloma

 Amgen Inc. said Wednesday the U.S. Food and Drug Administration approved Kyprolis in a combination regime to treat certain adult patients with relapsed or refractory multiple myeloma.

The company said the FDA expanded Kyprolis' prescribing information to include its use with Darzalex Faspro, or daratumumab and hyaluronidase-fihj, and dexamethasone to treat adults with relapsed or refractory multiple myeloma who have received one to three lines of therapy.

Amgen said the expansion was supported by an ongoing Phase 2 trial evaluating Darzalex Faspro in combination with four standard-of-care treatment regimens in patients with multiple myeloma.

https://www.marketscreener.com/quote/stock/AMGEN-INC-4847/news/Amgen-Says-FDA-Approves-Kyprolis-Combination-to-Treat-Multiple-Myeloma-37184855/

CVS started at Buy by Seaport

 Target $110

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

AstraZeneca to Scrap Plan for U.S. Covid Booster Study

 

AstraZeneca Plc is dropping plans to test its Covid-19 vaccine as a booster in the U.S., according to a letter sent to participants in the clinical trial that urged volunteers to seek a third dose elsewhere.

After discussions with the U.S. government, it became clear that the U.K. drugmaker was unlikely to pursue plans to assess a third dose of its vaccine, New York’s Montefiore Medical Center told trial participants on Tuesday.

“We learned this not long ago, and were hoping that there would be a formal announcement from AstraZeneca,” the letter said. “In the absence of a formal announcement, we are sending this information in the interest of your health.”

Astra, one of the first vaccine developers out of the gate, has yet to win clearance to sell the shot in the U.S. after facing questions about its clinical trial results and side effects. As a result, the product has taken a back seat to messenger RNA rivals made by Moderna Inc. as well as Pfizer Inc. and its German partner, BioNTech SE

Barry Zingman, the doctor overseeing the trial at Montefiore, advised participants in Astra’s vaccine trial who haven’t gotten a third shot to seek one outside the study, mentioning immunizations from Pfizer, Moderna and Johnson & Johnson. Volunteers who take one of these shots can still remain in the study, he said.

The performance of Astra’s vaccine, which was developed with the University of Oxford, as a booster will become clearer in coming days when the U.K. releases a study comparing the performance of seven different Covid shots administered as a third dose. 

A spokesperson for Astra declined to comment. It was unclear whether there would be an Astra booster, Montefiore said, and the hospital therefore encouraged patients to get a booster off-site in light of immunization recommendations from health authorities. 

https://www.bloomberg.com/news/articles/2021-12-01/astra-to-scrap-plan-for-u-s-booster-study-participants-told

    Moderna could have Omicron booster ready in March

     Moderna Inc could have a COVID-19 booster shot targeting the Omicron variant tested and ready to file for US authorization as soon as March, the company's president said on Wednesday.

    Moderna President Stephen Hoge said he believes booster shots carrying genes specifically targeting mutations in the newly-discovered Omicron variant would be the quickest way to address any anticipated reductions in vaccine efficacy it may cause.

    The company is also working on a multi-valent vaccine that would include up to four different coronavirus variants including Omicron.
    That could take several more months, he said.
    The United States identified its first COVID-19 case caused by the Omicron variant in California, the US Centers for Disease Control and Prevention said on Wednesday.
    Omicron, dubbed a "variant of concern" by the World Health Organization, is being studied to see if it is more contagious or causes more severe illness than other variants, and if it can evade current vaccines.
    Given prior guidance from the US Food and Drug Administration, which has required mid-stage clinical testing, Hoge said the process could take three or four months.
    "The Omicron-specific boosters, just realistically, are not before March and maybe more in the second quarter," Hoge said, unless the FDA changes its guidance for what data would be needed for authorization.
    Moderna would be able to manufacture the vaccine as it was conducting the testing, Hoge said, to have it ready to roll out as soon as possible.
    He said the FDA is currently assessing the threat to vaccine protection posed by the Omicron variant. The agency could provide a faster timeline, akin to the way it approves vaccines for influenza, by approving changes in the flu strains, which would shorten the three- to four-month timeline.
    In the United States, licensed flu vaccines can be updated each season by substituting in new strains of the virus that are believed to be most likely to cause illness in the upcoming flu season, without the need for large, randomized clinical trials.
    Based on the pattern of mutations seen in the Omicron variant, which include mutations that have already been shown to reduce the efficacy of its vaccine in lab studies, Hoge said, "we expect there will be an impact."
    It is not clear yet how big of a drop in efficacy the Omicron variant will cause for current vaccines, but it could be significant, Hoge surmised.
    "The mutations that had previously led to the biggest drops in efficacy were seen in Delta and Beta. And all of those mutations have shown up in Omicron," Hoge said.
    "And so the question here is, are we going to see a Delta-like performance? Are we going to see a Beta-like performance? Or are we going to see some cross multiple of the two? I think it's that last scenario that has people most concerned," he said.
    Hoge said the company is testing to see whether fully vaccinated recipients of Moderna's vaccine are protected against the variant, as well as those who received the 50-microgram and 100-microgram booster doses of the shot.
    "I still believe that the existing vaccines will be able to at least slow down, if not completely stop, the Omicron variant," he said.

    NYC private schools now mandating COVID-19 vaccines for all students

     Some of the city’s most exclusive private schools are leading the charge in mandating COVID-19 vaccines for all students, The Post has learned.

    Elite bastions including Spence, Chapin, and Horace Mann have all sent out letters in recent weeks informing parents of the requirement and issuing deadlines for students to get the jab.

    “The expectation is now for all Spence students ages 5-11 to have received their first dose of COVID vaccine before January 7, 2022, and to be fully vaccinated by February 11, 2022,” Spence’s Principal Bodie Brizentine wrote to parents last month.

    The school said it would field medical and religious exemption requests that were formally sought before this upcoming Monday.

    “No consideration of exemptions will be accepted after this date,” Brizentine cautioned.

    Horace Mann Head of School Thomas Kelly issued a similar letter mandating the vaccine for all students.

    Horace Mann Head of School Thomas Kelly told parents that they shouldn't be surprised by the school's new vaccine mandate.
    Horace Mann Head of School Thomas Kelly told parents that they shouldn’t be surprised by the school’s new vaccine mandate.
    James Messerschmidt

    “No one with children ages five through eleven should be surprised by the school’s decision to mandate the new Pfizer vaccine,” Kelly wrote in a November 5 email to parents.

    The Chapin School has also elected to require students to get the jab in order to maintain enrollment with a deadline of January 14.

    Most city private schools are expected to follow suit if they have not already established the mandate.

    “There is a lot of support for this and some dissenters as well,” a Chapin parent said. “There are definitely parents here who are hesitant. It will be interesting to see how it plays out.”

    The Chapin School will require all students to be vaccinate for COVID-19 by January 14.
    The Chapin School will require all students to be vaccinated for COVID-19 by January 14.
    J.C. Rice

    Mayor Bill de Blasio declined to require doses for students this academic year, arguing that his focus was on getting Department of Education employees vaccinated.

    Mayor-elect Eric Adams said in October that he would back mandatory student vaccinations shortly before they received FDA approvals.

    “We already have a system in place that states before you start school, you receive your vaccination. It is to protect the child and the student population,” Adams told WCBS Newsradio 880.

    City Catholic schools have encouraged parents to get their kids vaccinated against the coronavirus but have stopped short of requiring them.

    California Gov. Gavin Newsom was the first official to require the vaccine for public school students, with the mandate expected to take effect later this year.

    https://nypost.com/2021/12/01/some-nyc-private-schools-now-mandating-covid-vaccines-for-students/

    Why Top Virologist Is Concerned About Omicron

     For virologist Trevor Bedford, PhD, the past week has felt like January 2020 all over again.

    In those earliest days of the pandemic, as early modeling data on the transmissibility of the novel coronavirus started to roll in, "it was pretty clear what would happen," he said.

    "It was fairly easy to realize with those numbers that we were actually now on planet B, though so much of the world still thought we were on planet A," added Bedford, who was one of the first experts to raise alarms about community spread in the U.S. "When we got to March 2020, it became very obvious that we were on planet B now."

    Bedford spoke during a virtual panel hosted by his employer, Fred Hutch, a cancer research center in Seattle. He and other researchers were interviewed by Fred Hutch president and director Thomas Lynch Jr., MD, as well as comedian Trevor Noah, host of "The Daily Show." Bedford made those previous remarks to Noah.

    Bedford also told Noah that researchers back in January 2020 weren't willing to make calls despite the evidence mounting before them.

    "This phrase that I hate is, 'There is no evidence that...'" Bedford said. "'There's no evidence that the Alpha variant is more severe,' or 'There's no evidence that masks work.' When, really, it's that you don't have firm, hard evidence where you can say, 'Yes, this is definitely the case.'"

    "But you should, with the mix of evidence that you have, be able to say, 'Yes, we suspect that masks do work,' or 'We suspect that the Alpha variant is more severe,'" he noted.

    "People aren't willing to walk out on a limb enough [when it comes to] what they actually think," he added.

    Bedford also described to Noah what it was like to be at the forefront of getting coronavirus testing up and running in the U.S., noting that in February 2020, his lab had samples that indicated community spread but "we were being told not to test them."

    "We did anyway and discovered community transmission," he continued. "By genome sequencing of the virus, we were able to tell there were about 1,000 infections at that point rather than just one."

    So why is Bedford concerned about Omicron? He told Lynch that the number of mutations in the spike protein is "kind of wild."

    Other variants including Alpha, Beta, Gamma, and Delta have had "maybe eight or 10 mutations in the spike protein, and that's largely what's given them their advantageous phenotype. Omicron comes ... perhaps from an immunocompromised individual, with 30 mutations in the spike protein."

    "As soon as people were able to see that genome, it looked striking, it looked worrisome," he noted.

    The rapid spread in South Africa's Gauteng province is also a red flag, as it's rapidly replacing Delta, he said.

    "If you look at case counts over time, you get maybe three times the current rate of spread of Delta," he explained. "Delta [spread] was two times compared to previous variants."

    Taken together, the changes in the genome and the rapid rise in cases "had people very concerned for good reason."

    It will take about 2 weeks to get clearer information on Omicron's immune evasion via neutralization assays, though it "already seems like it will be different," he said.

    Bedford explained that the Beta and Mu variants, for instance, brought an eight- to 10-fold drop in antibody titers in neutralizing assays testing vaccinated immunity -- but fortunately, that hasn't had a large impact on vaccine efficacy.

    "What we're waiting for is to see what Omicron comes in at," he said. "Is it 20-fold? Is it 30-fold? We know 20-fold is very different from 50-fold. There's a very wide range of numbers that you could imagine for this drop."

    There's also the possibility that booster or third doses of the mRNA vaccines offer decent protection against Omicron, he noted.

    "We know from three doses you get a nice broadening of immune response, so it might be less of a drop with the three doses, but we don't know yet," he said. "We could get lucky and three doses will still protect against infection quite well. Or we might need to try to very quickly have an Omicron-specific booster and move that through the regulatory process."

    It's also possible, he added, that three doses won't confer protection against infection, but will prevent severe disease.

    Monoclonal antibody therapies, on the other hand, are likely to be affected, said Rachel Bender Ignacio, MD, MPH, a Fred Hutch expert who was also on the panel. That's because they target regions where Omicron has known mutations, she explained, and previous variants have caused similar problems for these therapies.

    But direct-acting antivirals like Merck's molnupiravir or Pfizer's ritonavir likely won't be affected, Bender Ignacio continued. Both of these target viral replication.

    "Omicron has a lot of mutations in the spike protein, but we really don't think that those mutations will have an effect on the way that the virus reproduces itself once it's inside the cell," she said.

    That's a sign of hope, as Bedford made a strong call that there will never be a "post-COVID" world.

    "People need to realize that it's going to be around forever," he said. "Every year, just like we have flu season, there will be COVID season. It's going to be a thing that we have to deal with every year."

    "We'll be working on better vaccines, on better ventilation, and on antivirals," he promised.

    https://www.medpagetoday.com/special-reports/exclusives/95948

    FDA approval tracker: November

     The FDA dished out three Pdufa extensions and four knockbacks in November, including a CRL for Beyondspring’s plinabulin in chemotherapy-induced neutropenia. Beyondspring said today that the FDA had requested a second clinical study of plinabulin; this news sent the company's shares down 55% in early trading and follows disappointing NSCLC data at Esmo. On the flip side, Biomarin’s Voxzogo gained accelerated approval in patients aged five and older with achondroplasia. Assessing final adult height is part of the post-marketing requirement and Biomarin has said it will use the ongoing open-label extension studies versus natural history for confirmatory data. Merck’s Keytruda also gained another string to its bow last month with an adjuvant approval in renal cell cancer. The decision came three weeks early and puts Keytruda further ahead of rivals, which will start reporting phase 3 data next year.

    Notable first-time US approval decisions in November
    ProjectCompanyIndication(s)2026e SBI ($m)Outcome
    Ciltacabtagene autoleucel
    (cilta-cel)

    Johnson & Johnson/
    Legend Biotech
    3L+ multiple myeloma1,692Extended to Feb 28 (updated analytical method)
    Voxzogo
    (vosoritide)
    BiomarinAchondroplasia720Approved (accelerated)
    Doria
    (risperidone ISM)
    Laboratorios Farmacéuticos ROVISchizophrenia375CRL (manufacturing inspection)
    Enpaxiq
    (pacritinib)
    CTI BiopharmaMyelofibrosis patients with severe thrombocytopenia368Extended to Feb 28
    (data submission)
    Livtencity
    (maribavir)
    TakedaPost-transplant cytomegalovirus infection in those that are refractory, with or without resistance355Approved
    Oleogel-S10
    (Filsuvez)
    AmrytEpidermolysis bullosa269Extended to Feb 28 (review of additional data analyses)
    ErwinazeClinigen/
    Porton Biopharma
    ALL patients who have developed hypersensitivity to E. coli-derived asparaginase211CRL
    Eohilia
    (TAK-721)
    TakedaEosinophilic oesophagitis188No decision yet
    PedmarkFennecCisplatin-induced ototoxicity for paediatric patients165CRL
    (manufacturing deficiencies)
    PreHevbrio
    (Sci-B-Vac)
    Opko Health/
    VBI Vaccines
    Hepatitis B164Approved
    Plinabulin + G-CSFBeyondspringPrevention of chemotherapy-induced neutropenia 138CRL
    (more data requested)
    Yutrepia (LIQ861
    /treprostinil inhalation powder)
    LiquidiaPulmonary arterial hypertension126Tentative approval*
    Cytalux
    (OTL38/
    pafolacianine sodium injection)
    On Target LaboratoriesAdjunct for identifying ovarian cancer during surgery-Approved
    Eprontia (topiramate oral solution
    /ET-101)
    Azurity Pharmaceuticals/
    Eton Pharmaceuticals
    Tonic-clonic seizures, partial-onset seizures, and as preventative treatment of migraine-Approved
    Besremi (ropeginterferon alfa-2b)PharmaessentiaPolycythemia vera-Approved
    Fyarro
    (ABI-009)
    Aadi BioscienceAdvanced malignant PEComa-Approved
    EpsolaySol-GelPapulopustular rosacea-No decision yet
    *Final FDA approval may occur in Oct 2022 or earlier upon resolution of ongoing litigation with United Therapeutics. SBI=sales by indication, CMC=chemistry, manufacturing and controls.
    Source: Evaluate Pharma & company releases.

     

    Advisory committee meetings in November
    ProjectCompanyIndicationOutcome
    LV-101
    (intranasal carbetocin)
    LevoHyperphagia, anxiety, and distress behaviours associated with Prader-Willi syndrome12-1 against approval
    MolnupiravirMerck/
    Ridgeback
    EUA for the treatment of mild to moderate Covid-19 in adults who are at risk for progressing to severe Covid-19 and/or hospitalisation13-10 for EUA
    Source: FDA adcom calendar, Evaluate Pharma.

     

    Supplementary and other notable approval decisions in November
    ProductCompanyIndication (clinical trial)Outcome
    Dyanavel XR tabletsTris PharmaADHDApproved
    Keytruda MerckAdjuvant treatment of RCC at intermediate-high or high risk of recurrence (Keynote-564Approved
    (3 weeks early)
    Pobevcy
    (BAT1706)
    (Avastin biosimmilar)
    Bio-Thera SolutionsMetastatic colorectal cancer (+ chemo), 1L non-squamous NSCLC, recurrent glioblastoma, met renal cell carcinoma (+ interferon alfa), persistent, recurrent or met cervical cancerNo decision yet
    Source: Evaluate Pharma & company releases. 

    https://www.evaluate.com/vantage/articles/events/company-events-snippets/us-fda-approval-tracker-november