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Wednesday, June 2, 2021

Novartis Kisqali: longest median overall survival in postmenopausal HR+/HER2- metastatic breast cancer

 -- MONALEESA-3 median overall survival (OS) results of 53.7 months

      underscore that Kisqali offers more life to postmenopausal women with 
      HR+/HER2- metastatic breast cancer (MBC) in addition to the OS benefit 
      demonstrated for premenopausal women as shown in MONALEESA-71,2 
 
   -- The relative risk reduction of death by 36% in the MONALEESA-3 first-line 
      (1L) postmenopausal population highlights that Kisqali is the only 
      CDK4/6i with proven OS for 1L in combination with fulvestrant1 
 
   -- Time to chemotherapy was delayed to 4 years (48.1 months) in 
      postmenopausal women taking Kisqali in combination with fulvestrant 
      compared to 2.4 years (28.8 months) for women receiving fulvestrant only1 
 
   -- MBC takes a life in the US approximately every 12 minutes, creating an 
      urgent need for treatment proven to extend life while preserving quality 
      of life3-6 
https://www.marketscreener.com/quote/stock/NOVARTIS-AG-9364983/news/Press-Release-nbsp-Novartis-Kisqali-R-reports-longest-median-overall-survival-in-postmenopausal-H-35500199/

Novartis Kymriah trial: strong response rates, safety profile in relapsed or refractory follicular lymphoma

  -- Primary analysis of ELARA trial demonstrated a 66% complete response rate

      and 86% overall response rate with one-time Kymriah infusion1 
 
   -- Robust response observed in heavily pretreated patients in critical need 
      of a potentially definitive treatment option1,2 
 
   -- No patients in ELARA trial experienced grade 3/4 cytokine release 
      syndrome, the most common side effect associated with CAR-T therapy1 
 
   -- Global regulatory submissions based on the ELARA trial on track for later 
      this year
https://www.marketscreener.com/quote/stock/NOVARTIS-AG-9364983/news/Press-Release-nbsp-Novartis-Kymriah-R-pivotal-trial-demonstrates-strong-response-rates-and-a-rema-35500399/

Developed Countries Lock Up Covid-19 Vaccines Through 2023

 The European Union, Canada and other developed countries have signed deals to get hundreds of millions of doses of Covid-19 vaccines and boosters over the next two years, furthering a divide between rich and poor countries.

Under the recent deals, Pfizer Inc. and BioNTech SE agreed to supply the European Union up to 1.8 billion doses of their vaccine through 2023, while agreeing to supply Canada up to 125 million doses.

Australia, Switzerland and Israel, meanwhile, are set to get Moderna Inc.'s shot through next year, and Switzerland has options for doses in 2023.

The agreements will ensure the countries, including some that failed to lock up sufficient supplies of the mRNA vaccines earlier this year, have enough supplies to inoculate residents and protect them against potentially elusive variants, while providing a sales windfall to the manufacturers.

Yet the deals once again leave out developing countries, many of which have fallen behind in vaccinating residents and struggled to contain the spread of the virus.

Moderna sees Covax, the global-health initiative intended to get doses to low-income countries, as its primary means to supply lower- and middle-income countries, a spokesman said. The company said last month it would deliver 34 million doses in the fourth quarter of 2021 to Covax, which has an option to purchase another 466 million doses next year.

Pfizer has pledged to provide 2 billion doses to low- and middle-income countries over the next 18 months, a company spokeswoman said. It also has agreed to provide 40 million doses to Covax this year for distribution, which have begun to reach more than a dozen countries, she said. Pfizer's commitment to ensure access to the vaccine "has never wavered," and it is talking with countries and stakeholders about improving access, she added.

About 6 billion doses have been purchased by more than two dozen rich nations and the European Union, according to the latest figures from the Duke University's Global Health Innovation Center, which tracks vaccine purchases. By comparison, the rest of the world has combined to purchase more than 3 billion doses.

Neither the countries nor the companies disclosed the terms of the recent deals.

Covid-19 vaccine sales are forecast to total $70 billion through next year for Pfizer and more than $27 billion for Moderna, according to Bernstein Research.

Bernstein estimates Pfizer and BioNTech charge between $18 and $19.50 a dose in developed markets, compared with $7.50 in developing markets. Moderna charges between $17 and $20 a dose, compared with $8 in developing markets, according to Bernstein.

The Pfizer-BioNTech vaccine's sales would make it among the top-selling pharmaceuticals of all time. AbbVie Inc.'s anti-inflammatory drug Humira has been the recent top seller, notching nearly $20 billion in 2018 sales.

The U.S. hasn't signed new supply deals, but its agreements with Pfizer and Moderna provide the option for future purchases. In the U.S., each company is slated to deliver 300 million doses by the end of July.

The EU deal would help the bloc resolve the vaccine procurement problems that hurt its vaccination efforts earlier this year.

EU residents and public-health experts criticized the bloc as ordering vaccines too slowly, partly because they didn't want to pay as much as Pfizer and Moderna sought, and favoring older vaccine technologies over new ones.

Limited supplies of the mRNA vaccines hit especially hard after some countries restricted use of shots from AstraZeneca PLC and Johnson & Johnson over safety concerns.

The recent deals suggest the two-dose vaccines from Pfizer and Moderna have become the vaccines of choice in developed nations. They also mean most of the developed world should have enough Covid-19 vaccine supplies for the next couple of years to protect all their residents.

The new EU deal builds on 600 million doses Pfizer agreed to deliver this year. Under the deal, Pfizer agreed to send an initial 900 million doses starting in December, and the EU has the option to buy another 900 million doses.

The new supply will be enough for the bloc's 450 million citizens to get four Pfizer-BioNTech doses, according to Bernstein.

Australia, which has about 25 million residents and recently stopped administering AstraZeneca's shot to people under age 50, said last month that Moderna would provide 10 million doses this year and 15 million booster shot doses next year. Earlier, the country had placed orders for 40 million doses for delivery this year.

Pfizer has said it expects to produce 3 billion doses this year, and at least 4 billion next year. Moderna said it is targeting manufacturing up to 3 billion doses next year.

Some developing nations have reached deals with mRNA vaccine makers for doses, though supplies probably aren't enough to vaccinate all their populations.

Paraguay, which counts more than 7 million residents, said last month it signed a supply deal for 1 million doses of the Pfizer-BioNTech vaccine. Botswana said in April that Moderna is providing the African country, which has more than two million people, 500,000 doses of its shot.

Of the approximate 50 supply deals that Pfizer and BioNTech have with countries and groups like Covax, about half are with low- and middle-income countries, according to Duke's Global Health Innovation Center.

Pfizer has said it would discount its vaccine to middle-income countries, while providing it at cost to poorer countries.

Six of the 19 Moderna deals are for low- and middle-income countries, according to the Duke center. Moderna has said it would price its vaccine in low-income countries at its lowest-tier price.

Many developing nations are still negotiating with Pfizer and Moderna, according to the companies. They also are waiting on doses from Covax and appealing to the U.S. government to provide excess doses.

Covax has been beset by manufacturing and delivery delays.

To access more doses, some developing countries have asked the World Trade Organization to waive patent protection for Covid-19 vaccines. The U.S. said it supports the move, though Germany and some other developed countries have opposed it. The drug industry is lobbying against the proposal, saying waiving patent protection wouldn't provide relief any time soon while straining raw material supplies.

Public-health and vaccine experts say developing countries need more supplies to vaccinate residents to contain the spread of the virus and protect against dangerous new variants that emerge.

Developed countries won't be able to fully reopen, the specialists added, unless developing nations are able to immunize a sufficient number of residents.

With developed countries securing more doses for the next few years, low- and middle-income countries will probably find themselves dependent on rich countries to share or reallocate doses, said Prashant Yadav, a senior fellow at the Center for Global Development who studies supply chains.

He said that, if the divergence persists, more countries will likely sign supply deals with China and Russia, which have been eagerly providing doses made by their manufacturers.

https://www.marketscreener.com/quote/stock/MODERNA-INC-47437573/news/Developed-Countries-Lock-Up-Covid-19-Vaccines-Through-2023-35503918/

AstraZeneca in talks to shift COVID-19 vaccine production to Catalent factory

 AstraZeneca Plc is in talks with the U.S. government to shift production of its COVID-19 vaccine from a troubled Baltimore plant to a factory owned by Catalent Inc, the New York Times reported, citing people familiar with the matter.

The British drugmaker has been on the lookout for an alternative production site since the U.S. government stopped it from using Emergent BioSolutions Inc's Baltimore plant after workers accidentally contaminated a batch of Johnson & Johnson's vaccine with ingredients from AstraZeneca's that was also being produced at the time.

AstraZeneca's vaccine, approved in dozens of countries except United States, has been under increased scrutiny over reports of extremely rare but serious blood clots in the brain in some people who received the vaccine.

New Jersey-based Catalent will make use of its factory in Maryland where it already produces drug substance used in AstraZeneca's vaccine, the NYT report said on Wednesday.

AstraZeneca did not immediately respond to Reuters request for comment, and Catalent declined to comment.

https://www.marketscreener.com/quote/stock/ASTRAZENECA-PLC-4000930/news/AstraZeneca-nbsp-in-talks-to-shift-COVID-19-vaccine-production-to-Catalent-factory-NYT-35503394/

Morphosys mortgages its future

 It is worrying when a company once known for in-house development apparently has to resort to buying in late-stage development candidates – and perhaps more so when it raises the cash to do so by pawning the family silver. 

Certainly this is how Morphosys shareholders have reacted to the group's $1.7bn buyout of Constellation Pharmaceuticals, funded via a royalty-sharing deal with Royalty Pharma; Morphosys shares fell 16% at the open. But an analysis of Evaluate Pharma data suggests that this deal might not be all that unwise.

The purchase

Morphosys is paying $34 per share in cash for Constellation, a cancer-focused group whose lead candidate is pelabresib (CPI-0610), a BET inhibitor in a phase 3 trial in myelofibrosis. Constellation also has CPI-0209, an EZH2 inhibitor, in phase 2 in solid tumours and lymphoma, plus a couple of preclinical programmes. 

Though the price per share came in at a 68% premium to Constellation’s close yesterday it is worth noting that Morphosys waited until its target was off the boil. In mid-February Constellation’s stock was trading at nearly $37. 

Upon the Constellation acquisition closing, Morphosys’s other deal kicks in. Royalty Pharma will hand over $1.4bn up front and give Morphosys access to up to $350m in development funding bonds, which can be drawn over the course of a year, plus potential milestones. 

The price

In return, Royalty Pharma gets a generous share of Morphosys’s income: all of its royalties on Tremfya, the psoriasis blockbuster licensed to Johnson & Johnson, for a start. It will also receive shares of any future royalties on three of Morphosys’s clinical projects as well as two of Constellation’s.

But a look at the net present value of these assets, as calculated by Evaluate Omnium, suggests that Royalty has either paid over the odds or has major faith in what these projects can achieve. 

Crunching the numbers on Morphosys's Constellation deal
ProjectPhase and indicationNPV attributable to Morphosys% to go to Royalty PharmaTotal
TremfyaMarketed, plaque psoriasis and psoriatic arthritis $731m100% royalties$731m
OtilimabPh3 in rheumatoid arthritis; Ph2 in Covid-19 $82m90%*$74m
GantenerumabPh3, Alzheimer's$4m60% royalties$2m
Pelabresib/CPI-0610 (Constellation)Ph3, myelofibrosis$1,548m3% of sales$46m
CPI-0209 (Constellation)Ph1/2, solid tumours and diffuse large B-cell lymphomaN/A3% of sales$0m
NPV attributable to Royalty Pharma$854m
Total paid by Royalty Pharma$1,425m
*80% royalties & 100% of milestones to go to Royalty. Source: Evaluate Omnium, clinicaltrials.gov & company release.

If the sellside’s forecasts for these compounds are accurate Royalty’s up-front fee alone is worth $571m more than its share of their royalties is likely to bring in. 

Does Royalty know something equity analysts do not? It must reckon that the assets still in R&D can succeed beyond what the sellside models – a brave bet indeed considering that one of them, gantenerumab, is in development for Alzheimer’s. 

https://www.evaluate.com/vantage/articles/news/deals/morphosys-mortgages-its-future

FDA approval tracker: May

 Last month ended with a flurry of US FDA decisions and one, the green light for Amgen’s Lumakras, came over two months early. The accelerated approval in NSCLC patients with a Kras G12C mutation was given to the 960mg dose; a 240mg dose is the subject of a postmarketing study to see whether it has a similar clinical effect. Two other oncology drugs gained first-time accelerated approvals: J&J’s Rybrevant and Bridgebio’s Truseltiq. Both have confirmatory trials under way. After two previous complete response letters it was finally good news for Heron’s pain therapy Zynrelef, an extended-release bupivacaine combined with the anti-inflammatory meloxicam. To try and gain market share Heron is pricing Zynrelef at a 22-28% discount to Pacira’s Exparel; Evercore ISI analysts note that this price will also allow Heron’s drug to compete with generic bupivacaine. With May now over all eyes rest on aducanumab’s June 7 Pdufa, the biggest regulatory event of the year (Go or no go? Aducanumab’s day of reckoning, May 27, 2021).

Notable first-time US approval decisions in May
ProjectCompanyIndication2026e sales by indication ($m)Outcome
Lumakras
(sotorasib)
AmgenNSCLC with Kras G12C mutation after at least one systemic therapy1,756Approved (~2.5mth early, accelerated)
Myfembree (relugolix)MyovantUterine fibroids490Approved
Zynrelef
(HTX-011)
Heron TherapeuticsPost-op pain relief471Approved
Lybalvi
(ALKS 3831)
AlkermesSchizophrenia and bipolar 1 disorder380Approved
Empaveli (pegcetacoplan)ApellisPNH (including treatment naive)309Approved
Truseltiq
(infigratinib)
Bridgebio Pharma2L cholangiocarcinoma253Approved (accelerated)
Rybrevant
(amivantamab)
J&JNSCLC with EGFR exon 20 insertion mutations250Approved (~2mth early, accelerated)
Pylarify (PyL)Lantheus HoldingsProstate cancer diagnostic imaging agent233Approved
Zonisamide oral suspensionEton/Azurity PharmaceuticalsPartial seizures in epilepsy-No decision yet
Dehydrated alcohol injection (DS-100)EtonMethanol poisoning-CRL (CMC)
CamceviForesee PharmaceuticalsAdvanced prostate cancer-Approved
Source: Evaluate Pharma & company releases.

 

Advisory committee meetings in May
ProjectCompany2026e sales by indication ($m)OutcomeNote
Vynpenta
(avacopan)
Chemocentryx639Efficacy vote split (9-9), safety profile and benefit-risk votes slightly in favour (10-8)ANCA-associated vasculitis, Pdufa in July (Chemocentryx’s future in doubt as avacopan foundation crumbles)
Teplizumab
(PRV-031)
Provention Bio-Voted 10-7 that benefits outweigh risks in support of approval Delay of clinical type 1 diabetes in at-risk individuals (Provention’s diabetes project takes a tentative step forward)
Source: Evaluate Pharma & FDA adcom calendar

 

Supplementary and other notable approval decisions in May
ProductCompanyIndication (clinical trial)Outcome
OpdivoBristol Myers SquibbAdjuvant oesophageal/gastroesophageal junction cancer (Checkmate-577)Approved
ZeposiaBristol Myers SquibbUlcerative colitis (True North)Approved
Nurtec ODTBiohavenPrevention of migraine (Study 305201)Approved
FerriproxChiesiTransfusional iron overload due to sickle cell disease or other anaemias in adults and paediatrics aged 3 and olderApproved
Keytruda + Herceptin + chemoMerck & Co1L Her2+ gastric or gastroesophageal junction adenocarcinoma (Keynote-811)Approved (accelerated)
CosentyxNovartisModerate-severe plaque psoriasis in children and adolescents (NCT03668613NCT02471144)Approved
NuzyraParatekOral only dosing regimen for the treatment of community-acquired bacterial pneumoniaApproved
MSB11455 (Neulasta biosimilar)FreseniusReduce the incidence of infection associated with febrile neutropeniaNo decision yet
EsbrietRocheUnclassifiable interstitial lung disease (NCT03099187)No decision yet
AubagioSanofiPaediatric relapsing MS (Terikids)No decision yet
AlecensaRocheFirst-line Alk-positive NSCLC (Bfast)No decision yet
Source: Evaluate Pharma & company releases.

 

FDA Covid-19 EUAs
ProductCompany2026e sales by indication ($m)Note
ComirnatyPfizer1,784Expanded to include 12 to 15-year-olds
Sotrovimab
(VIR-7831)
Vir/GSK1,212Treatment of mild-moderate Covid-19 in adults and paediatrics (US appetite for Covid-19 treatments remains undiminished)
Source: Evaluate Pharma & company releases.

https://www.evaluate.com/vantage/articles/news/snippets/us-fda-approval-tracker-may-0

Biggest Challenge Biogen Will Face if Its Alzheimer's Drug Is Approved

 A crucial decision is days -- or maybe even hours -- away for Biogen (NASDAQ:BIIB). By June 7, the Food and Drug Administration will decide whether to approve the biotech company's controversial Alzheimer's drug candidate. A positive decision seems crucial for Biogen because the company predicts declining sales of its big multiple sclerosis blockbuster and is in need of a new growth driver.

If the FDA gives the nod to the Alzheimer's candidate, aducanumab, it's very likely Biogen shares will soar. More than 6 million Americans suffer from the disease, and treatment options are extremely limited. But Biogen might not get the major revenue boost it's hoping for even if aducanumab wins approval. Let's look at the biggest challenge the company could face.


Patient groups and families eagerly await the aducanumab regulatory decision. If approved, it would be the only treatment known to reduce declines in daily function and cognition. But Biogen's challenge may be convincing doctors to prescribe aducanumab to their patients.

Why would doctors refuse to prescribe such a treatment? Many are hesitant due to the drug candidate's clinical trial path. I'll explain:

Biogen halted clinical trials of aducanumab in early 2019. This came after a futility study saying the treatment was unlikely to work. The company surprised investors later in the year when it revived the program -- and said it soon would file for regulatory approval.

The reason for such a turnaround? Biogen conducted a post-study analysis of its two phase 3 trials. Initially, the trial named Emerge met its primary endpoint. It showed a reduction in clinical decline. Researchers measure that by looking at cognition and daily function. The trial named Engage didn't meet this endpoint. But in the post-study analysis, Biogen looked at a group of some Engage participants who received higher doses of the drug candidate. And those participants showed a reduction in clinical decline, the company said.

Are the data enough?

Since Biogen reinstated the aducanumab program, analysts and doctors have argued about whether data from a post-study analysis are strong enough to support regulatory approval. In fact, an FDA advisory committee that was convened late last year even voted against approving the drug candidate. The FDA considers the opinion of this panel of experts but isn't obliged to follow it.

If we look at market potential without the idea of whether doctors will or won't prescribe the drug, it's big. Aducanumab could generate about $4.9 billion in annual sales by 2026, according to the news site EvaluatePharma. And some news reports cite analyst estimates of at least $10 billion in annual sales.

Now, let's get back to the subject of what doctors will decide to do. Right now, it's fair to say that aducanumab is controversial and some healthcare professionals aren't convinced of its efficacy; the FDA advisory committee vote is an example of that. A report co-authored by Dr. David S. Knopman, a site investigator in the aducanumab trials, calls for another phase 3 trial of aducanumab to support the idea of a higher dose.

So, what does this mean for Biogen?

If the FDA approves aducanumab, Biogen investors surely will cheer. It does offer the company another revenue opportunity. But I would have preferred that Biogen took its time with this one and conducted another phase 3 trial, as Dr. Knopman and his fellow authors recommend. Right now, if aducanumab is approved, Biogen may face an uphill battle winning over the majority of doctors. Another phase 3 trial with strong results would have made it much easier to convince doctors of the drug's merit.

This doesn't mean a potential aducanumab approval would be bad news. But it does mean the drug's success isn't guaranteed. And if success does happen, it will take time. Meanwhile, if revenue disappoints in the first couple of quarters, shares of this biotech giant might suffer.

So if you're a Biogen shareholder (or want to become one), it's important to keep an eye on these first quarters. They would offer us clues about whether doctors are willing to give the product a chance -- and whether Biogen may indeed have a major new revenue driver.

https://www.fool.com/investing/2021/06/02/heres-the-biggest-challenge-biogen-will-face-if-it/