Lilly Delivers Q1 Financial Results, Adjusts 2021 Guidance

  Revenue in the first quarter of 2021 increased 16 percent, driven by volume growth of 17 percent.

- First-quarter 2021 revenue grew 7 percent excluding revenue of $810.1 million from COVID-19 antibodies and also excluding first-quarter 2020 revenue of approximately $250 million from increased customer buying patterns and patient prescription trends.

- Key growth products, consisting of Trulicity, Verzenio, Olumiant, Tyvyt, Emgality, Jardiance, Retevmo, Cyramza and Taltz, contributed 8 percentage points of revenue growth and represented approximately 46 percent of total revenue in the first quarter of 2021, or 52 percent of total revenue excluding revenue from COVID-19 antibodies.

- First-quarter 2021 operating expenses increased 11 percent, driven primarily by higher research and development investments, including expenses of $220 million to develop COVID-19 therapies. Excluding investment in COVID-19 therapies, total operating expense growth was less than 3 percent.

- Notable pipeline events included Emergency Use Authorization from the FDA for bamlanivimab and etesevimab together for the treatment of COVID-19, as well as positive data readouts for tirzepatide for type 2 diabetes, donanemab for Alzheimer's disease, mirikizumab for ulcerative colitis and baricitinib for alopecia areata.

- First-quarter 2021 earnings per share (EPS) decreased to $1.49 on a reported basis and increased to $1.87 on a non-GAAP basis.

- 2021 EPS guidance lowered to be in the range of $7.03 to $7.23 on a reported basis and adjusted to be in the range of $7.80 to $8.00 on a non-GAAP basis.

 Investors and the general public can access a live webcast of the first-quarter 2021 financial results conference call through a link on Lilly's website at www.lilly.com. The conference call will begin at 9:00 a.m. Eastern time (ET) today and will be available for replay via the website.

https://www.prnewswire.com/news-releases/lilly-delivers-first-quarter-2021-financial-results-adjusts-2021-financial-guidance-301277287.html

Top U.S. trade negotiator meets Pfizer, AstraZeneca execs on COVID-19 IP waiver

 U.S. Trade Representative Katherine Tai on Monday met virtually with top executives of drugmakers Pfizer and AstraZeneca PLC to discuss a proposed waiver of certain intellectual property rights in response to the COVID-19 pandemic.

Members of the World Trade Organization are due to discuss a proposal by India and South Africa to waive certain provisions of the WTO's Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) on April 30, but the United States and a few other big countries have blocked such a move.

Democratic lawmakers, civil society groups, and 60 former heads of state and 100 Nobel Prize winners have urged President Joe Biden to back the waiver. White House Press Secretary Jen Psaki on Monday said she had no updates on the issue.

Tai's meetings with the Pfizer and AstraZeneca executives reflect her intense engagement on the issue, and follow similar meetings with advocacy groups, industry executives and others.

Earlier this month, Tai told a WTO meeting the gaping divide between developed and developing countries' access to medicines was "completely unacceptable" and industry needed to make sacrifices in times of crisis.

In her discussion with Pfizer Chief Executive Dr. Albert Bourla, Tai emphasized her commitment to working with other members of the WTO on a global response to the crisis, her office said in a statement.

That included "the role of developing countries in any solution that addresses critical gaps in global production and distribution of vaccines," USTR said.

Tai also discussed the issue with Dr. Ruud Dobber, head of U.S. business at AstraZeneca, as well as the White House's decision to share up to 60 million doses of AstraZeneca's COVID-19 vaccine with countries in need.

USTR said Tai and Dobber discussed "increasing vaccine production, global health issues and the proposed waiver."

https://news.yahoo.com/top-u-trade-negotiator-meets-012920214.html

Do pharma buyouts hurt innovation and lead to higher prices? Analyst counters FTC stand

 In recent years, Democratic commissioners at the U.S. Federal Trade Commission (FTC) have clashed with their Republican counterparts over the agency's standards for large biopharma transactions. Now that they’ve come into power under the Biden administration, the Democrats have launched a sweeping review that threatens to clamp down on industry deal-making.

One influential biopharma analyst disagrees with the FTC's stated reasoning for implementing tougher reviews. In fact, the new stance could be counterproductive, he argued.

Large pharma consolidation can hurt R&D and lead to higher drug prices, Democratic commissioners have said. But those concerns are unfounded, SVB Leerink analyst Geoffrey Porges countered in a recent note to clients.

“[I]n fact, many of their arguments, if turned into industrial or FTC policy, would result in less innovation, less competition, and less choice for consumers,” Porges wrote.

There’s simply no evidence that larger companies raise drug prices faster than small companies do, Porges wrote. Instead, small companies often have few options in their toolbox and therefore tend to resort to price increases to invigorate performance. Large firms have more “skin in the game” in the overall healthcare system and have been more careful, he argued.

In her dissenting opinion opposing Bristol Myers Squibb’s $74 billion acquisition of Celgene, FTC acting chair Rebecca Kelly Slaughter noted that "branded drug prices have increased substantially in recent years, and pharmaceutical merger activity persists at a high pace.”

Still, the question is, does M&A lead to faster drug price increases? After digging into recent buyouts, Porges found a range of possible outcomes.

Drugs he examined include blood cancer drugs Revlimid and Pomalyst from Bristol’s acquisition of Celgene; Otezla, which Amgen bought from Celgene; PARP inhibitor Zejula, the centerpiece of GlaxoSmithKline’s purchase of Tesaro; cancer combo drugs Braftovi and Mektovi as part of Pfizer’s purchase of Array BioPharma; and pulmonary arterial hypertension drugs Opsumit and Tracleer, which Johnson & Johnson picked up with Actelion.

Among them, Amgen's Otezla’s 2021 price increase came in higher than the med's prior-year price hike. Pfizer's first list price increases for Braftovi and Tracleer ticked up, but the magnitudes have since trended down. For the other meds, new owners didn't raise prices as much as prior owners.

Ultimately, clamping down on drug prices does more to stifle innovation than M&A, Porges said. The analyst criticized the “shallowness” of the regulators’ view as serving a political objective—namely, lowering drug prices—rather than trying to protect competition.

“The recent flowering of innovation in the biopharmaceutical industry in the U.S. is mainly based on an assumption of free pricing and open market access, thus providing a (somewhat) predictable return for investing in innovation,” Porges said.

Larger companies can be more efficient on the R&D front because their efforts are spread across multiple products and candidates, Porges said. When a company's cost structure is based around just one product, prices either need to be higher or R&D investment lower to support commercialization, he said.

Overall, Porges believes Slaughter’s view of the negative effects from pharma M&As won’t prevail in the courts and therefore won’t likely become the FTC’s standard in the long run. In the short term? Companies will be more cautious about transactions “mainly because of the cost, time and ultimately reputational risk of dealing with extended review and litigation against the FTC,” he wrote.

https://www.fiercepharma.com/pharma/large-pharma-m-as-hurt-innovation-drug-price-analyst-counter-ftc-s-arguments-for-stricter

Gottlieb: US should ‘lean more aggressively forward’ to lift COVID restrictions

 The former head of the Food and Drug Administration said the US should “lean more aggressively forward” into lifting COVID-19 restrictions — adding that he believes the trend of declining cases is “locked in at this point” and he doesn’t anticipate another surge.

“I think oftentimes a mistake we make is that we’re quicker to implement these precautions than we are to lift them because we’re worried that once we lift them, we won’t be able to reimplement them,” Dr. Scott Gottlieb said Sunday on CBS’ “Face the Nation.”

“I think we need to lean more aggressively forward and look at ways to try to relax some of the provisions that don’t really make as much sense anymore.”

Gottlieb said officials should look the “hardest” at restrictions on outdoor activities.

“I think we should be thinking about lifting mask ordinances outside. I think we should be thinking about lifting limits on gatherings outside and trying to encourage people to go outside now that the weather is warming, take more activities outside in the face of declining risk overall,” he said.

Gottlieb said the US doesn’t need to be as concerned this time around that when “we take out foot off the brake, things are going to surge again.”

“I think that these declines we’re seeing are really locked in at this point,” Gottlieb said, noting that this comes despite contagious variants such as B117 becoming dominant.

“People, by and large, are engaging in a lot of activity. B117 is epidemic across the country and we’re still not seeing big surges. And that’s a good indication,” he continued.

Dr. Scott Gottlieb says one area that should be closely examined for looser restrictions is outdoor activities.

Getty Images

Though states have reopened before only to see surges, Gottlieb said the situation is different now due to more of the population having immunity from vaccines and prior infections.

“Right now, the declines that we’re seeing, we can take to the bank,” he said.

“I think we could feel more assured because they’re being driven by vaccinations and greater levels of population-wide immunity, not just from vaccination, but also from prior infection. There’s been a lot of Americans who’ve had this infection and have a level of immunity from their prior disease.”

https://nypost.com/2021/04/26/ex-fda-head-us-should-aggressively-lift-covid-restrictions/

Gilead to Donate a Minimum of 450,000 Vials of Remdesivir to India

 Gilead Sciences Inc. intends to donate to India at least 450,000 vials of an antiviral drug that is used as a Covid-19 treatment in response to the surge of coronavirus cases in that country.

Late last year, the World Health Organization recommended against the use of remdesivir, the antiviral drug for Covid-19 made by Gilead, after concluding that there wasn't evidence that the drug reduced deaths or recovery times.

In 2020, Gilead reported about $2.8 billion in sales from remdesivir, which sells under the brand name Veklury.

On Monday, Gilead said licensees based in India were already stepping up production and that it would continue to support the expansion of local production capacity, offering technical assistance to voluntary licensing partners and donating the active pharmaceutical ingredient, or API, to rapidly scale up production of remdesivir.

To safeguard against disruption of generic remdesivir supply to other low- and middle-income countries, Gilead said it would offer similar support, including donating the active pharmaceutical ingredient, to those voluntary licensees.

https://www.marketscreener.com/quote/stock/GILEAD-SCIENCES-INC-4876/news/Gilead-to-Donate-a-Minimum-of-450-000-Vials-of-Remdesivir-to-India-33073719/

Common IBS/IBD treatment blunts COVID-19 vaccine response

 People who take a commonly prescribed drug for inflammatory bowel disease (IBD) should not assume they are protected after a first dose of COVID-19 vaccine, after a large-scale study found many had poor antibody responses.

The research measured antibody responses after vaccination with the Pfizer/BioNTech or the Oxford/AstraZeneca COVID-19 vaccine in 865 people treated with infliximab, an anti-tumor necrosis factor (anti-TNF) biologic drug, prescribed to around two million people worldwide. Anti-TNF drugs are effective treatments for immune-mediated inflammatory diseases, but by suppressing the immune system, they can reduce vaccine effectiveness and increase risk of serious infection.

Led by the University of Exeter and the Royal Devon and Exeter NHS Foundation Trust, and published in GUT, the paper is an output from the CLARITY Study is funded by the NIHR and Crohn's and Colitis UK. The research found that people treated with infliximab had significantly lower concentrations of antibodies, when compared to 428 people on an alternative treatment, vedolizumab.

Vaccines work by stimulating the immune system to produce antibodies that protect individuals from any future infection. For a vaccine to be effective, it needs to trigger a sufficient number of virus-targeting antibodies to prevent any subsequent infection.

After a single dose of vaccine, only about one third of participants (103 of 328) treated exclusively with infliximab generated adequate levels of antibodies to the virus for the vaccine to be considered effective. In participants simultaneously taking infliximab and immunomodulator drugs, such as azathioprine or methotrexate, the levels of antibodies were even lower after a single vaccine dose; only 125 of 537 met the threshold of a positive antibody test.

However, in a sub-group of people who had previously been infected with COVID-19, and also in the few patients studied who had already had a second dose of vaccine, the vaccine-triggered antibody responses rose significantly, indicating an effective response after two exposures. Based on these observations, the researchers conclude that people taking anti-TNF drugs should be considered a priority for a second vaccination.

The CLARITY study recruited 6,935 patients with Crohn's disease and ulcerative colitis from 92 UK hospitals between September and December 2020, to investigate the impact of these drugs on COVID-19 susceptibility and protective immunity that follows infection or vaccination. Previously, the study found that infliximab blunts the immune system to COVID-19 infection, potentially increasing the risk of reinfection.

CLARITY study lead Dr. Tariq Ahmad said the current findings had important implications for people treated with anti-TNF therapy, particularly for those also treated with an immunomodulator. He said "Poor antibody responses to a single dose of vaccine exposes these patients to a potential increased risk of COVID-19. However, we found much higher antibody levels in people vaccinated after a previous COVID-19 infection and in the small number of patients who had received two vaccine doses suggesting that all patients receiving these drugs should be prioritized for optimally timed second doses."

500,000 people across the UK live with Inflammatory bowel disease (IBD) of which ulcerative colitis and Crohn's disease, are the two main forms. Symptoms include urgent and frequent bloody diarrhoea, weight loss, pain, and extreme fatigue. At the start of the COVID-19 pandemic the UK Government advised that patients taking anti-TNF medicines could be at increased risk of complications from coronavirus. All were advised to follow strict social distancing measures, and some, depending on the severity of their condition, were advised to shield.

Co-author Dr. Nick Powell, of Imperial College London, said: "Although we know that this has been an incredibly difficult time for people with IBD, our research indicates that people treated with infliximab should consider that they are not protected from COVID-19 until they have had both doses of a vaccine and should continue to practice enhanced physical distancing and shielding if appropriate."

In the study, a small sub-set of patients showed no antibody response even after two exposures to COVID-19. Co-author Dr. James Goodhand, of the University of Exeter, said: "Our findings come as countries across Europe are opting to delay the second dose of vaccine. We recommend prioritizing second doses to patients taking anti-TNF drugs, who will remain at high risk after their first dose. Further data are needed to investigate whether we should be testing antibody concentrations after two doses to identify the small number of patients who have not responded well to vaccination."

The study also found evidence that antibody responses were lower in current smokers and participants aged 60 or older, but higher in non-white participants. These findings warrant further investigation in larger studies before firm conclusions can be drawn.

Sarah Sleet, Chief Executive of Crohn's & Colitis UK, said: "This is the first robust evidence that people with Crohn's and Colitis—who may need to take specific drugs to suppress their immune system—do not develop the expected antibodies after their first vaccination dose, although a second dose does improve antibody levels. With 1 in 5 not developing antibodies even after two doses, these people will be desperately worried that they remain at risk of catching COVID–19 and may develop a more serious illness at a time when shielding has ended. We need urgent research on the optimal time between the first and second jabs, and the need to be prioritized for any booster jab this Autumn."

The paper is entitled "Infliximab is associated with attenuated immunogenicity to BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines in patients with IBD' .

Infliximab helped Rachel into IBD remission—yet now affects her COVID-19 protection

For Rachel Sawyer, infliximab brought welcome relief from a decade of hugely restrictive inflammatory bowel disease symptoms.

Rachel, 52, was diagnosed with Crohn's disease in 2000. As her conditioned worsened, she had to adapt her lifestyle and her social life diminished as she became increasingly housebound and too tired to go out.

"You just feel exhausted, and also very low a lot of the time" said Rachel, a communications manager who lives in Farnborough, Hampshire. "If you go out, you have to plan a circuitous route to make sure you're never too far from a toilet—a lot of the time it's just not worth it so you stay home, which has a further impact in lowering your mood.

"Infliximab was a real game-changer. I'd been so scared about taking medication, but I had to do something and my consultant persuaded me. Within six months, it made a real benefit. I had a colonoscopy and it showed real improvement. I've been in remission for nine years now, although I'm still taking infliximab."

During COVID-19, Rachel has taken particular precautions around distancing, mask wearing, hand washing and going out, although stopped short of shielding. She said: "The lack of interaction has a huge impact on people's mental health; ultimately you have to weigh up your own risk and circumstances. I've certainly been taking extra care, in line with the advice from the CLARITY study.

"It is worrying that people on infliximab aren't protected after one vaccine dose, but it's also reassuring that protection increases after a second dose. We don't have control over when we get our second dose, so we now need to push for a campaign to ensure governments recognize that people on infliximab should be prioritized for a second dose in good time.

"While the findings from the research may be daunting for some IBD patients, particularly those on infliximab, they will not essentially change my behavior. That said, I will continue to be diligent in my efforts to protect myself and others by practicing social distancing, mask wearing and handwashing. Above all, I will be guided by the science that's provided by CLARITY and other world-leaders in IBD research and I hope other patients will follow suit."

More information: Nicholas A Kennedy et al. Infliximab is associated with attenuated immunogenicity to BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines, Gut (2021). DOI: 10.1101/2021.03.25.21254335

https://medicalxpress.com/news/2021-04-common-ibsibd-treatment-blunts-covid-.html

Certain antibiotics can prevent the entry of SARS-CoV-2 into cells

 The Drug Design and Molecular Topology Unit group of the University of Valencia has shown that certain macrolide antibiotics (used in respiratory tract infections), including clarithromycin and azithromycin, can prevent the entry of SARS-CoV -2 in cells. The study, led by Professor of Physical Chemistry Jorge Gálvez, has been published in the prestigious North American Journal of Chemical Information and Modeling.

The group already pioneered an article in March 2020, proposing such antibiotics as drugs that could be targeted to treat COVID-19. However, this prediction was only based on theoretical computational calculations. The method was based on molecular topology, a part of mathematical chemistry that deals with the algebraic description of chemical compounds, which allows them to be easily characterized.

Now, in collaboration with researchers from the National Center for Biotechnology (CSIC), they have shown with their study that these antibiotics are capable of preventing the entry of the virus in vitro by deactivating the well-known spike protein.

The group has had the collaboration of José María Benlloch Baviera (CSIC), coordinator of the treatment and vaccines area of the PTI Global Health platform for the development of treatments and vaccines of the CSIC.

Currently, of the antibiotics identified by the Drug Design and Molecular Topology Unit of the University of Valencia, one of them (azithromycin) is part of the list of drugs considered essential by the Ministry of Health in the management of the health crisis caused by COVID-19. Another, clarithromycin, is already scheduled to be used in a clinical trial led by the San Carlos Clinical Hospital of Madrid, which is expected to begin shortly with COVID patients from 20 primary care centers of the Social Security.

Methodology

To confirm the computational results of the initial phase, the best candidates were tested against two human coronaviruses (229E-GFP and SARS-CoV-2) in cell culture. Infection experiments demonstrated that azithromycin, clarithromycin, and lexithromycin reduce intracellular viral RNA accumulation and virus spread, as well as prevent virus-induced cell death, by inhibiting the entry of SARS-CoV-2 into cells.

More information: Jorge Galvez et al. Macrolides May Prevent Severe Acute Respiratory Syndrome Coronavirus 2 Entry into Cells: A Quantitative Structure Activity Relationship Study and Experimental Validation, Journal of Chemical Information and Modeling (2021). DOI: 10.1021/acs.jcim.0c01394

https://medicalxpress.com/news/2021-04-antibiotics-entry-sars-cov-cells.html