Stocks started September on a positive note on Tuesday, with S&P futures flat after fading earlier gains alongside shares in Europe as global indexes close to all-time highs as data in China and Europe showed manufacturing demand rebounding from coronavirus-induced lows. The dollar tumbled to a two-year low and the Yuan jumped after Chinese manufacturing data indicated that exports are underpinning a recovery.
The MSCI world equity index, which tracks shares in 49 countries, was close to recent highs, while the pan-European Stoxx 600 rose 0.3% in early trading with technology and basic resources climbing the most among sectors. France’s Cac 40 was up 0.2% and Germany’s Dax was up 0.7%. Britain’s FTSE 100 lagged, down 1.4%, hurt by a rising pound. Euro zone manufacturing activity grew last month, though factory managers remained wary about investing and hiring more workers. The French Mfg PMI beat expectations coming at 49.8, above the 49.0 consensus if down from 52.4, while Germany output grew at its fastest pace since February 2018, while in France it contracted.
European stocks had opened even higher but pared gains after Germany cut its GDP forecast for 2021. Both shares and the euro, which rose to a two-year high of $1.19975 overnight in New York, were little changed after data showed annual euro zone inflation fell well below expectations in August, turning negative for the first time since May 2016, and a far cry from the European Central Bank’s inflation target of just under 2% (some have mused if the ECB will follow the Fed in announcing AIT as well).
“These numbers are clearly inconsistent with the ECB’s target,” said George Buckley, chief European economist at Nomura, who said the low reading will raise questions about whether the ECB should, like the Fed, adopt average inflation targeting. There were however credibility issues with such an approach, if the bank was unable to raise inflation to balance out the periods of lower inflation.
In Asia, China’s yuan touched the highest since 2019 and equities benchmarks in Hong Kong, Shanghai, Taipei and Seoul climbed. The Caixin PMI survey of China’s factory activity rose at the fastest pace in August since January 2011, helped by improving exports and continued domestic recovery, and boosted market sentiment overnight and into the European market open.
In rates, 10Y yields rose to 0.72% , up 2bps on the day with treasuries trading heavy led by the long end as month-end bid unwound. Yields were cheaper by up to 3bp at long end of the curve, steepening 2s10s, 5s30s by 1.6bp and 2.7bp; 10-year yields around 0.725%, cheaper by 1.8bp vs Monday’s close while gilts lag by ~1.5bp across the sector. Gilts underperformed, weighing on Treasuries along with a sharp selloff in Aussie bonds during Asia session. Core euro zone bond yields were up around 1 to 2 basis points, with the benchmark German 10-year yield at -0.387%.
In FX, the dollar continued to drop to a fresh two-year low and was down 0.4% at 91.826, dropping below 92 for the first time since May 2018 after a purchasing managers index for China beat estimates to raise optimism over Asia’s economic recovery.
"The weakness in the dollar is likely to continue and I suspect it will be substantially weaker from where it is against the euro by the end of the year," said Savvas Savouri, chief economist at Toscafund Asset Management. "We’ve got the Fed chairman clearly telling us he wants inflation to ratchet upwards, and the only reliable way to achieve this is through the channel of a weaker currency."
The euro climbed after German unemployment eased for a second month, though gains fell short of reaching $1.20 following the abovementioned deflationary print. At 1025 GMT, the single currency traded at $1.19835, up 0.4% since New York’s close as a dollar sell-off continued. Sterling rose to eight-month highs against the dollar, strengthening to as much as $1.3465 at 1028 GMT, and was up around 0.3% versus the euro.
In commodities, oil prices gained, reversing overnight losses. Brent climbed 56 cents to $45.84 a barrel while WTI futures rose 47 cents to $43.08 a barrel. Gold prices also rose, to their highest in two weeks.
- S&P 500 futures up 0.3% to 3,510.75
- STOXX Europe 600 up 0.2% to 367.28
- MXAP up 0.4% to 173.35
- MXAPJ up 0.5% to 574.03
- Nikkei down 0.01% to 23,138.07
- Topix down 0.2% to 1,615.81
- Hang Seng Index up 0.03% to 25,184.85
- Shanghai Composite up 0.4% to 3,410.61
- Sensex up 0.8% to 38,948.09
- Australia S&P/ASX 200 down 1.8% to 5,953.41
- Kospi up 1% to 2,349.55
- German 10Y yield rose 0.9 bps to -0.388%
- Euro up 0.3% to $1.1971
- Italian 10Y yield rose 5.0 bps to 0.968%
- Spanish 10Y yield rose 0.8 bps to 0.417%
- Brent futures up 1.2% to $45.82/bbl
- Gold spot up 1.1% to $1,989.57
- U.S. Dollar Index down 0.3% to 91.91
Top Overnight News from Bloomberg
- A private gauge of China’s factory activity grew at the fastest rate in August since January 2011, helped by exports and domestic recovery
- Global trade is expected to rebound faster than after the 2008 financial crisis, according to Germany’s Kiel Institute for the World Economy. The number of coronavirus cases approaches 25.5 million worldwide, while deaths surpass 850,000
- The euro zone’s inflation rate went negative for the first time since 2016. Meanwhile Germany’s hit from the coronavirus will be less severe than feared, as the government’s efforts to kick start Europe’s largest economy show signs of bearing fruit
- A closely-watched euro-area interbank borrowing rate fell to a record, dragged down by all the money sloshing around the economy
A quick look at global markets courtesy of NewsSquawk:
Asian equities traded cautiously as the region took its cue from the losses seen across most global counterparts despite Wall St. notching its biggest monthly gain since April and its best August performance in more than 3 decades, while participants also digested encouraging Chinese Caixin Manufacturing PMI data. ASX 200 (-1.8%) underperformed and briefly wiped out all of the prior month’s gains on a collapse below the 6,000 level with the downturn led by hefty losses in tech and energy, while the detention of a Chinese-Australian television anchor further highlighted the souring bilateral relations with China. Nikkei 225 (-0.1%) was indecisive but with downside stemmed by recent currency weakness and political continuity hopes with Chief Cabinet Secretary Suga said to be supported by the largest faction of the ruling LDP and is set to announce an intention to continue with Abenomics and the pandemic response when declaring his candidacy on Wednesday. Elsewhere, Hang Seng (U/C) and Shanghai Comp. (+0.4%) swung between gains and losses as mild support was seen following the strongest Caixin Manufacturing PMI reading since January 2011, but with upside also capped after the PBoC drained CNY 230bln from the interbank market and due to lingering US-China tensions after White House trade adviser Navarro stated the US will go after others not just TikTok and WeChat. Finally, 10yr JGBs were higher following the recent gains in T-notes and indecisive risk tone in the region, although some of the gains were reversed after all metrics pointed showed weaker results at the 10yr JGB auction.
Top Asian News
- Total Enters Giant Korean Floating Wind Projects in Green Push
- Samsung’s Heir Jay Y. Lee Indicted in Succession Probe
- Supreme Court Approves 10-Year Rescue Plan for Indian Telcos
- SoftBank Corp. Is ‘Surprise’ Addition to Japan’s Nikkei 225
Earlier gains across European equities have somewhat faded (Euro Stoxx 50 +0.4%) despite a lack of fresh macro catalysts, with the region now ultimately mixed, whilst losses in UK’s FTSE 100 (-1.3%) persist amid a catch-up play from its long weekend Bank holiday. Sectors performance is also varied with no clear risk profile to be derived: the IT sector outperforms as chip-makers cheer reports that Apple is aiming to launch four new iPhone models next month, with volumes in the 75mln region. Thus, the likes of STMicroelectronics (+1.1%), Dialog Semiconductor (+3.3%), Infineon (+1.2%) remain propped up. On the other side of the spectrum resides Travel & Leisure, alongside Banks and Oil & Gas. In terms of individual movers, Novartis (+3.0%) keeps the healthcare sector afloat on the back of a broker upgrade at Morgan Stanley coupled with an announcement that it has developed new ESG targets in order to ramp up access to medicines and achieve full carbon neutrality. Sticking with the healthcare sector, Sanofi (+0.6%) has largely brushed off its COVID-19 Kevzara vaccine failing to meet primary and key secondary endpoints in its Phase III trials. Meanwhile, AstraZeneca (-0.5%) succumbs to the weakness in the post-bank holiday UK markets but with downside somewhat cushioned by a positive update for its Farxiga, Imfinzi and COVID-19 vaccine deal with Canada. Elsewhere, Shell (-2.0%) and BP (-2.1%) are subdued despite higher oil prices, and with losses more pronounced that its cross-border counterparts amid catch-up play alongside reports UK Chancellor Sunak could increase fuel duty by 5p to help pay for the coronavirus in the Autumn budget.
Top European News
- U.K. Manufacturing Output Expands at Fastest Pace in Six Years
- European Factories Brace for Economic Rebound to Falter
- Russia Passes 1 Million Covid-19 Cases as Epidemic Simmers
- German Joblessness Falls Again Amid Revival of Economic Activity
In FX, the Dollar is suffering from a post-month end hangover as the DXY slips to a new 2020 low of 91.741 amidst broad losses vs G10 peers and most EM currencies. Confirmation of a firm US manufacturing PMI via the final release and ISM matching expectations for a pick-up in headline activity could conceivably provide the Greenback some respite, but the index remains toppy on rebounds over 92.000 as buoyant risk sentiment counters renewed bear-steepening along the Treasury curve.
- NZD/CAD/GBP/EUR - The major beneficiaries of ongoing Buck weakness as the Kiwi pivots either side of 0.6750 awaiting NZ terms of trade for Q2 and the Loonie extends through the psychological 1.3000 level with some assistance from firm crude oil. Meanwhile, the Pound has scaled another big figure and briefly breached a mid-December 2019 peak (1.3422), as Eur/Gbp unwinds modest RHS demand for the August/September turn from circa 0.8950 towards 0.8900 irrespective of more negative sounding Brexit news (EU chief negotiator Barnier reportedly unwilling to discuss new UK fishing proposals unless Britain compromises on other contentious issues). Elsewhere, the Euro has tested round number resistance at 1.2000 vs the Dollar, but market contacts note heavy offers related to option expiries and on that note 1.1 bn rolling off between 1.1895-1.1900 at today’s NY cut may keep the headline pair supported given little net reaction to mixed Eurozone manufacturing PMIs and even weak, deflationary inflation.
- JPY/AUD/CHF - Also firmer against the Greenback, albeit mildly as the Yen hovers midway within a 106.03-105.60 range, the Aussie fades after another 0.7400+ foray and Franc fails to breach 0.9000. For the record, the RBA stuck to the script overnight, though did extend and expand its Term Funding Facility, while July building approvals smashed estimates and the Q2 current account surplus was wider than forecast. However, relations with China are going from bad to worse as barley imports from Australia’s CBH Grain company are suspended.
- SCANDI/EM - Not much response to rises in Swedish and Norwegian manufacturing PMIs, but China’s stronger than expected Caixin reading has helped the Yuan appreciate further vs the Dollar in contrast to a decline in the Turkish headline index that is weighing on the already lagging Try.
In commodities, WTI and Brent front month futures continue to ebb higher in early European trade, in what is a continuation of price action seen overnight as a function of the weakening Dollar, whilst the complex also remains underpinned by overall risk sentiment. Aside from that, pertinent news flow has been on the light side, although sources reported that UAE’s ADNOC pumped some 2.693mln BPD of crude in August in order to meet domestic demand – above its quota under the OPEC+ pact. That being said, sources added that the country will compensate for the undercompliance in the months ahead, whilst Iraq submitted a plan to OPEC that proposes additional cuts of 400k BPD in August and September and Kazakhstan plans additional cuts of 95k BPD over the same two-month period, according to sources. Further, Goldman Sachs raised 2020 Brent crude price forecast to USD 43.63/bbl from USD 40.51/bbl and raised 2021 forecast to USD 59.38/bbl from USD 55.63/bbl. WTI October holds its head above USD 43.00/bbl having found an overnight base around USD 42.75/bbl, whilst its Brent counterpart inches higher towards 46/bbl from a low of 45.47/bbl. Elsewhere, the weaker Buck keeps precious metals afloat with spot gold inching higher towards the USD 2000/oz mark (vs. low 1965/oz) whilst spot silver extends gains above USD 28.75/oz (vs. low 28.04/oz). Meanwhile, LME copper prices climbed to levels last seen over two years ago – bolstered by the Chinese Caixin Manufacturing beat coupled with the softer Dollar, whilst Dalian iron ore saw mild gains due to the same factors.
US Event Calendar
- 9:45am: Markit US Manufacturing PMI, est. 53.6, prior 53.6
- 10am: ISM Manufacturing, est. 54.8, prior 54.2
- 10am: Construction Spending MoM, est. 1.0%, prior -0.7%
- Wards Total Vehicle Sales, est. 15m, prior 14.5m
DB's Jim Reid concludes the overnight wrap
Never has the restrictions of social distancing felt so liberating. As of today I can break the shackles of two weeks in quarantine. It’s been tedious, tiresome and ponderous. As least during full lockdown we went out for a nice walk once a day and I had heaps of work to occupy me. Of these past 14 days, 10 were spent on holiday at home (or weekends) and 4 at work in my home office. The latter were infinitely more enjoyable and less stressful for me. Much less for my wife. Every morning the twins repeatedly say “Go Mummy car”. They can’t work out why we don’t go out and are very confused. Hopefully they’ll squeal with delight when they realise their wish is finally going to come true.
So with a dull second half of August behind me we welcome in September today. To mark this we are launching our monthly survey this morning as a back to school special. This month’s includes plenty of questions about life around the virus including some questions on whether you will be first up volunteering to take any vaccine, whether you think they should be compulsory and how your understanding is on the effectiveness of vaccines generally. Also a number of other questions. It only takes 3 mins to fill in and results will come in the days ahead. Here is the link. All help filling in the survey very much appreciated.
This morning Henry is publishing the monthly performance review. It was another good month for risk especially for Silver (+15.39%) and the Nasdaq (+9.59%). It was also the best August for the S&P (+7.01%) since 1986 and the best individual month since April - just after the pandemic lows. See the full review in your inboxes soon for more.
Even with the good month, August ended with the S&P 500 slipping slightly, falling -0.16%, as even large gains in tech stocks were unable to keep the index in the green. Roughly 70% of the index was lower on the day after stocks dipped mid-session on reports of China blocking US companies from buying social media company TikTok. In a story that speaks to the power of retail investing in the current market, Apple and Tesla powered the Nasdaq +0.68% higher to another record after their pre-announced stock splits were enacted. The two stocks added +3.39% and +12.57% of value respectively by just lowering the sticker price.
In Europe with the UK markets closed, the Stoxx 600 fell -0.62% during the last session of August, reversing a gain of as much as +0.7% early in the session. This left the index up +2.86% on the month for its best August performance since 2009. Core sovereign bonds diverged much like equities with US 10yr Treasury yields down -1.6bps to finish at 0.705%, while 10yr Bund yields rose +1.2bps to -0.40%. The dollar resumed its slide as well (-0.25%), falling for the fifth session in a row.
Overnight Asian markets are a little directionless with the Nikkei (-0.07%) and Hang Seng (-0.02%) trading flat while the CSI (+0.12%) and Shanghai Comp (+0.04%) are posting modest advances. The Kospi (+1.06%) is leading the way on news that the government is preparing to boost its 2021 budget by 8.5%. In FX, all G-10 currencies are up (0.2-0.6%) against the greenback with the Euro trading closer to the 1.20 handle at 1.1992. Meanwhile the onshore Chinese yuan is up +0.42% to 6.8202, the highest level in over a year. Futures on the S&P 500 are up +0.11% while those on the Nasdaq are up +0.40%. Elsewhere, crude oil prices are trading up c.1% this morning while gold and silver are up +0.91% and +1.81% respectively.
It’s another round of global PMIs today and we’ve already kicked things off in Asia with China’s Caixin manufacturing PMI printing at 53.1 (vs. 52.5 expected and 52.8 last month), the highest reading since Jan 2011 and further emphasising the China recovery story. Yesterday, we saw China’s official August PMIs with manufacturing printing 0.2pts lower than expectations at 51.0 while services were at 55.2 (vs. 54.2 expected). Back to today and Japan’s final manufacturing PMI reading was confirmed at 47.2 (vs. 46.6 in flash). South Korea also showed an improvement at 48.5 (vs. 46.9 last month) while for Taiwan it was at 52.2 (vs. 50.6 last month), the highest reading in 2 years. However, readings for Vietnam (at 45.7 vs. 47.6 last month) and Australia (at 53.6 vs. 53.9 in flash and 54.0 last month) retreated on account of renewed lockdowns during the past month.
Following the policy framework changes laid out by Fed Chair Powell last week, yesterday Federal Reserve Vice Chair Clarida spoke to the possibility of using Treasury yield caps at some point, but suggested that it is not currently in the plans. He also noted that it is appropriate in many circumstances for inflation to overshoot the 2% goal. Markets also heard from the Fed's Bostic, who said that he was ‘very worried' about the drop in fiscal support for economy. Given that several participants argued for more accommodation in July, a lack of fiscal response and further gridlock may cause more committee members to opt for additional easing. With the next FOMC in two weeks this meeting will slowly come into the market’s view.
On the coronavirus, yesterday news came that Paris will now offer free testing at various locations throughout the city in order to identify and contain the spread of infections within the French capital. Cases in the country grew by 35,000 in the last week which is almost as many as seen at the country’s April peak, but there has not yet been a significant change in hospitalisations. The pace of new cases in the US continues to slow even as confirmed cases passed 6 million. Earlier this month New York City mayor said that indoor dining would be closed until June 2021, and then yesterday added that any resumption of indoor dining may hinge on a “huge step forward” such as a vaccine. With no guarantee of an effective or widely administered vaccine and colder months coming, this could lead to lower mobility and business output from the largest US city. Across the other side of world, India is now undoubtedly the global epicenter of the virus with the rise in new cases topping 70k on a daily basis. It also has the third highest fatalities now at 64,469. A reminder that we still publish our daily tables in the full pdf if you click on “view report”.
There was a good deal of attention on the US Presidential race this weekend after the conclusion of the Republican National Convention last Thursday night. We will see what kind of polling bounce President Trump receives, if any, by the end of the week as very few polls currently include the final, higher profile nights of the convention. In 2016, President Trump saw a nearly 5pt improvement in head-to-head polls against Secretary Clinton after the RNC. He even led her in polling averages for a small amount of time before seeing the bounce decline within a month. That said, Mr. Trump has seen his poll numbers vs Mr. Biden improve by nearly 2.8ps over the past 6 weeks. The RealClearPolitics polling average measures his nadir at 40pts in mid-summer. Mr. Trump is now back to the head-to-head polling range of 42-44pts he was sitting at following the first wave of outbreaks in the US. Overall RCP measures a +6.9pt spread for Mr. Biden (49.7%) over Mr. Trump (42.8%) but check in later this week to see how the RNC may change that.
Today we get final August manufacturing PMI’s from around the world, along with the ISM readings from the US, which will give us an indication of how the global economy has fared through the month as some economies opened up further and some became more restricted as viral patterns differed around the world. Note that the flash readings for the Euro Area saw a loss of momentum in the early part of August as its composite PMI fell from 54.9 to 51.6. Outside of the PMI’s, we will get July unemployment data out of the Euro Area, Italy and Japan, while seeing August unemployment change from Germany.
Back to this week’s calendar and later in the week the main highlights are the corresponding services and composite PMIs (Thursday) as well as the US jobs report on Friday. On payrolls, consensus on Bloomberg is currently expecting a further +1.518m increase in nonfarm payrolls last month, which would bring the total growth in nonfarm payrolls to 10.797m since April trough. However that would still be less than half of the 22.16m jobs lost in March and April. We have the day by day highlights for the rest of the week at the end.
To quickly recap last week for those on holiday yesterday, global equity markets continued to rise as the Federal Reserve’s new inflation targeting approach percolated through the financial system late in the week. The S&P 500 finished up +3.26% (+0.67% Friday) over the course of the week, having closed at record highs for 6 sessions in a row. The index has now risen 8 of the last 9 weeks since coronavirus cases rose quickly throughout the Southern and Western United States in June. The tech-focused Nasdaq rose +3.39% (+0.60% Friday) finishing at fresh highs as well and is now up over 30% YTD. In Europe, equities lagged behind their US counterparts, but the Stoxx 600 ended the week +1.02% (-0.52% Friday) higher.
Core sovereign bonds fell significantly on the week, before gaining on Friday with yields near their highest levels since June. The US yield curve steepened significantly following Fed Chair Powell’s statement on Thursday around the policy review and average inflation targeting. US 10yr Treasury yields rose +9.3bps (-3.1bps Friday) to finish at 0.721%, the highest weekly close since late March. Meanwhile 10yr Bund yields rose a similar +9.8bps (-0.2bps Friday) to -0.41% and 10yr Gilts rose +10.5bps (-2.5bps Friday) to 0.31%. The US 2y10y yield curve steepened +10.9bps to the highest levels since early June. In other markets, the dollar fell -0.94% on the week and is set to finish August lower for a fifth straight month.
Breaking the tape
The top performers among drugs launched in 2020 were each the first of their kind.
Breaking the tape
The top performers among drugs launched in 2020 were each the first of their kind.
By Joshua Slatko • firstname.lastname@example.org
The leaders in pharma’s Class of 2020 were all firsts. Veklury, for COVID, and Tepezza, for thyroid eye disease, were each the first drug of any kind to be approved by FDA for their respective disease targets. And while other treatments for migraine exist, Ubrelvy was the first orally administered calcitonin gene-related peptide (CGRP) receptor antagonist (gepant) for the treatment of migraine attacks once they start. The era of follow-ons in pharma may not entirely be over; but surely the industry’s researchers are still breaking barriers.
The very first drug to be approved in the United States for the treatment of COVID-19, Gilead’s Veklury received emergency use authorization from FDA during May 2020, an expanded EUA three months later, and full approval for treating patients with COVID requiring hospitalization during October 2020. Veklury had originally been developed for the treatment of hepatitis C and had been studied in Ebola and Marburg virus, without success.
FDA approval was based on three randomized controlled trials including final results of the National Institute of Allergy and Infectious Diseases’ double blind, placebo-controlled Phase III ACTT-1 trial, which showed that treatment with Veklury resulted in clinically meaningful improvements across multiple outcome assessments compared with placebo in hospitalized patients with COVID-19. Based on the strength of these data, Veklury became a standard of care for the treatment of COVID-19 in hospitalized patients.
In the randomized, double-blind, placebo-controlled ACTT-1 trial, Veklury significantly improved time to recovery as compared to placebo – by five days in the overall study population (10 versus 15 days) and seven days in patients who required oxygen support at baseline (11 versus 18 days). As a secondary endpoint, Veklury also reduced disease progression in patients needing oxygen, resulting in a significantly lower incidence of new mechanical ventilation or ECMO (13 percent versus 23 percent). In the overall patient population, there was a trend toward reduced mortality with Veklury compared with placebo at Day 29.
In June 2021, Gilead announced positive data from three retrospective studies of the real-world treatment of patients hospitalized with COVID-19, adding to the body of mortality and hospital discharge data for patients treated with Veklury. All three of the real-world analyses observed that, in the overall patient populations, patients who received Veklury treatment had significantly lower risk for mortality compared with matched controls. A reduction in mortality was observed across a spectrum of baseline oxygen requirements. The results were consistently observed at different time frames over the course of the pandemic and across geographies. Two of the studies also observed that patients who received Veklury had a significantly increased likelihood of discharge from the hospital by Day 28.
In January 2022, FDA granted expedited approval of a supplemental new drug application for Veklury for the treatment of non-hospitalized adult and adolescent patients who are at high risk of progression to severe COVID-19, including hospitalization or death. The expanded indication allowed for Veklury to be administered in qualified outpatient settings that can administer daily intravenous infusions over three consecutive days. FDA also expanded the pediatric EUA of Veklury to include non-hospitalized pediatric patients younger than 12 years of age who are at high risk of disease progression.
These actions by FDA came amidst a surge in COVID-19 cases and the reduced susceptibility to several anti-SARS-CoV-2 monoclonal antibodies (mAbs) due to the Omicron variant. In contrast, Veklury targets the highly conserved viral RNA polymerase, thereby retaining activity against existing SARS-CoV-2 variants of concern. In vitro laboratory testing has shown that Veklury retains activity against the Omicron variant.
The FDA sNDA approval, pediatric EUA expansion, and updated National Institutes of Health Treatment Guidelines for COVID-19 that additionally recommend Veklury for treatment in non-hospitalized settings were based on results from the PINETREE Phase III randomized, double-blind, placebo-controlled trial. The study evaluated the efficacy and safety of a three-day course of Veklury for intravenous use for the treatment of COVID-19 in non-hospitalized patients at high risk for disease progression. An analysis of 562 participants randomly assigned in a 1:1 ratio to receive Veklury or placebo, demonstrated that treatment with Veklury resulted in a statistically significant 87 percent reduction in risk for the composite primary endpoint of COVID-19 related hospitalization or all-cause death by Day 28 (0.7 percent, 2/279) compared with placebo (5.3 percent, 15/283). In the study, no deaths were observed in either arm by Day 28.
In February, Gilead released data demonstrating the in vitro activity of Veklury against 10 SARS-CoV-2 variants, including Omicron. Results of Gilead’s studies were consistent with other in vitro studies independently conducted by researchers from institutions in other countries, including Belgium, the Czech Republic, Germany, Poland and the United States, which confirmed Veklury’s antiviral activity against multiple previously identified variants of SARS-CoV-2, including Alpha, Beta, Gamma, Delta and Omicron.
The study analyzed in vitro antiviral activity by two methods to understand the susceptibility of 10 major SARS-CoV-2 variants to Veklury. The study results showed similar activity of Veklury against the variants and an early ancestral A lineage isolate detected in Seattle, Wash. (WA1 strain). Specifically, Delta and Omicron variants both remained fully susceptible to Veklury, and these laboratory results demonstrated that Veklury has remained active against all major variants isolated over the past two years.
In April, FDA approved a supplemental new drug application for Veklury for the treatment of pediatric patients who are older than 28 days, weighing at least 3 kg, and are either hospitalized with COVID-19 or have mild-to-moderate COVID-19 and are considered high risk for progression to severe COVID-19, including hospitalization or death. This approval made Veklury the first and only approved treatment for pediatric COVID patients in the United States. Under the expanded indication, a three-day Veklury treatment regimen is recommended to help prevent hospitalization in non-hospitalized COVID-19 pediatric patients who are at high risk for COVID-19 disease progression. For hospitalized pediatric patients who do not require invasive mechanical ventilation and/or ECMO, a five-day treatment course is recommended. The approval was supported by results from the CARAVAN Phase II/III single arm, open-label study, which demonstrated that Veklury was generally well-tolerated among pediatric patients hospitalized with COVID-19 with a high proportion of participants showing clinical improvement and recovery, as well as data from trials in adults.
When it earned approval in January 2020, Horizon Therapeutics’ Tepezza became the first and only FDA-approved medicine for thyroid eye disease, a serious, progressive and vision-threatening rare autoimmune disease that is associated with proptosis (eye bulging), diplopia (double vision), blurred vision, pain, inflammation, and facial disfigurement. Tepezza is a fully human monoclonal antibody (mAb) and a targeted inhibitor of the insulin-like growth factor-1 receptor (IGF-1R) that is administered to patients once every three weeks for a total of eight infusions.
The FDA approval of Tepezza was supported by a robust body of clinical evidence, including statistically significant, positive results from the Phase II clinical study, as well as the Phase III confirmatory clinical study OPTIC. The OPTIC study found that significantly more patients treated with Tepezza (82.9 percent) had a meaningful improvement in proptosis (≥ 2 mm) as compared with placebo patients (9.5 percent) without deterioration in the fellow eye at Week 24. Additional secondary endpoints were also met, including a change from baseline of at least one grade in diplopia (double vision) in 67.9 percent of patients receiving Tepezza compared to 28.6 percent of patients receiving placebo at Week 24. In a related analysis of the Phase II and Phase III clinical studies, there were more patients with complete resolution of diplopia among those treated with Tepezza (53 percent) compared with those treated with placebo (25 percent).
In October 2020, Horizon announced new long-term follow-up data from the Phase II clinical trial of Tepezza, which showed a sustained response up to one year following completion of treatment for thyroid eye disease. All patients with Week 72 data (37/37) reported some improvement in at least one of the study outcomes from baseline. 97 percent (36/37) of study participants had an improvement in clinical activity score (decrease of at least 1 point). 86 percent (31/36) had any decrease in proptosis. One patient chose elective TED surgery at Week 70 and did not have proptosis measurements at Week 72. Of patients with baseline diplopia, 70 percent (23/33) had an improvement of at least one grade. 70 percent (26/37) had disease inactivation (CAS of 0 or 1 point).
During December 2020, Horizon announced that the company expected a short-term disruption in Tepezza supply as a result of government-mandated COVID-19 vaccine production orders related to Operation Warp Speed that dramatically restricted capacity available for the production of Tepezza at its drug product contract manufacturer, Catalent. In March 2021, FDA cleared a prior approval supplement to the previously approved Biologics Licensing Application giving Horizon authorization to manufacture more Tepezza drug product resulting in an increased number of vials with each manufacturing slot. The company began to resupply the market in April, which ended the supply disruption.
In April 2021, new pooled data from the Tepezza Phase II and III trials was published in The Lancet Diabetes & Endocrinology. This data further reinforced that Tepezza significantly improves proptosis and diplopia for TED patients in different subgroups, with most maintaining a long-term response. There was no evidence for acute disease rebound (increase in percentage of patients no longer meeting proptosis, diplopia or ophthalmic composite outcome) seven weeks after the last dose of Tepezza. Proptosis (87 percent; 62/71), diplopia (66 percent; 38/58) and ophthalmic composite outcome (92 percent; 66/72) responses were observed seven weeks after the last dose of Tepezza. A post-hoc analysis of the composite ophthalmic outcome indicated that 81 percent (68/84) of Tepezza patients versus 44 percent (38/87) of placebo patients were responders at Week 24. Proptosis (67 percent; 38/57), diplopia (69 percent; 33/48) and composite outcome response (83 percent; 48/58) were observed 51 weeks after the last dose of Tepezza for those who had long-term off-treatment data available.
Additionally, in a post-hoc analysis, Tepezza-treated patients with more severe disease (those with ≥3 mm of proptosis and/or inconstant or constant diplopia) and those with less severe disease at baseline both experienced significant improvements in proptosis and diplopia. In patients with more severe disease, those treated with Tepezza had a proptosis response of 79 percent (50/63) compared to 17 percent (11/65) of those who received placebo, and a diplopia response of 68 percent (38/56) compared to 31 percent of those who received placebo (15/49). In patients with less severe disease, those treated with Tepezza had a proptosis response of 71 percent (15/21) compared to 9 percent in those who received placebo (2/22), and a diplopia response of 80 percent (8/10) compared to 30 percent in placebo (3/10).
In post-hoc analyses, patients who received Tepezza in both the lower baseline CAS subgroup (4 or 5) and the higher CAS subgroup (6 or 7) demonstrated statistically significant improvements compared with placebo in proptosis and diplopia. Overall response and CAS of 0 or 1 response also improved.
Post-hoc analysis from the Phase III study also demonstrated that in patients treated with Tepezza, those with higher (≥10 IU/L) or lower (<10 IU/L) serum thyrotropin-binding inhibitory immunoglobulin (TBII) baseline levels both had a proptosis response (mean reduction of -3.65 mm and -3.01 mm, respectively) with no treatment difference between the two groups. In patients with higher baseline TBII, 71 percent (10/14) of patients who received Tepezza experienced an improvement in diplopia compared to 23 percent (3/13) of patients who received placebo.
In November 2021, Horizon announced findings of a real-world adherence analysis of Tepezza for the treatment of TED. The analysis found that more than 90 percent (n=995) of people who were prescribed Tepezza for TED went on to complete all eight infusions, indicating a high level of adherence to the medicine in clinical practice. The study evaluated 1,101 people living with TED (71 percent female, mean age 58 years) who started treatment with Tepezza prior to July 2020. Non-compliance was low at approximately 1 percent (n=15). Only 8 percent (n=84) reported that they discontinued because of adverse events.
In June 2022, Horizon announced results of a new analysis examining rates of hyperglycemia among patients treated with Tepezza for TED compared to placebo in the Phase II and OPTIC Phase III clinical trials. The analysis found a total of nine adverse event reports of hyperglycemia in eight patients (8/84, 10 percent) who received Tepezza, and one patient (1/86; 1.2 percent) who received placebo. The majority (5/8, 63 percent) of patients who experienced hyperglycemia while taking Tepezza had pre-existing diabetes. Of the hyperglycemic AEs reported in the Tepezza-treated patients, all were controlled with medicine. All reported AEs were grade 1 (>ULN-160mg/dl) or grade 2 (161 – 250mg/dl), and none led to study discontinuation. HbA1c levels increased by 0.22 percent in those treated with Tepezza compared to 0.04 percent among placebo patients.
Approved by FDA in late December of 2019, Ubrelvy was the first orally administered calcitonin gene-related peptide (CGRP) receptor antagonist (gepant) for the treatment of migraine attacks once they start. Ubrelvy works by blocking CGRP, a protein that is released during a migraine attack, from binding to its receptors. It works without constricting blood vessels, which some older treatments were known to do. FDA’s approval was based on four clinical studies (ACHIEVE I, ACHIEVE II, UBR-MD-04, and 3110-105-002), which demonstrated efficacy, safety, and tolerability of orally administered Ubrelvy in the acute treatment of migraine. Both 50 mg and100 mg dose strengths demonstrated significantly greater rates of pain freedom and freedom from the most bothersome migraine-associated symptom at two hours, compared with placebo. Ubrelvy joined AbbVie’s portfolio when that company completed its acquisition of Allergan in May 2020.
In August 2020, AbbVie announced Serena Williams as the spokesperson for Ubrelvy to raise awareness of an effective acute treatment option for people living with migraine. The multichannel marketing campaign featuring Williams highlighted how Ubrelvy works for people with different lifestyles by helping individuals treat their migraine attacks anytime, anywhere. As spokesperson, she was featured in a video, available on social media, talking with neurologist and paid AbbVie consultant Dr. Jennifer McVige about her experience with migraine and Ubrelvy. Williams was also included in print and digital advertising and other marketing initiatives.
In September 2021, FDA approved AbbVie’s Qulipta, another drug from the gepant family, for the preventive treatment of episodic migraine in adults. Qulipta is the first and only oral calcitonin gene-related peptide receptor antagonist specifically developed for the preventive treatment of migraine. The approval was supported by data from a robust clinical program evaluating the efficacy, safety, and tolerability of Qulipta in nearly 2,000 patients who experienced 4 to 14 migraine days per month, including the pivotal Phase III ADVANCE study, the pivotal Phase IIb/III trial, and the Phase III long-term safety study.
In the pivotal Phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group ADVANCE trial, the primary endpoint was change from baseline in mean monthly migraine days across the 12-week treatment period. All Qulipta dose groups met the primary endpoint and demonstrated statistically significant reductions in mean monthly migraine days compared to placebo. Patients treated with 60 mg of Qulipta across 12 weeks experienced a 4.2-day reduction from baseline of 7.8. A key secondary endpoint in the ADVANCE trial measured the proportion of patients that achieved a ≥50 percent reduction in monthly migraine days across the 12-week treatment period. The trial demonstrated that 56 percent/59 percent/61 percent of patients in the 10 mg/30 mg/60 mg Qulipta arms, respectively, achieved a 50-100 percent reduction, compared to 29 percent of patients in the placebo arm.
During June, AbbVie submitted a supplemental NDA to FDA for Qulipta to support the preventive treatment of chronic migraine in adults. If approved, Qulipta would be the first gepant cleared for the broad indication of the preventive treatment of migraine, including episodic and chronic. The supplemental NDA submission includes data from the pivotal Phase III PROGRESS trial in patients with chronic migraine, which supplements the existing data in episodic migraine. People living with chronic migraine experience headaches for 15 or more days per month, which, on at least eight of those days per month, have the features of migraine.
The Phase III PROGRESS trial met its primary endpoint of statistically significant reduction from baseline in mean monthly migraine days compared to placebo across the 12-week treatment period in adults with chronic migraine. The trial also demonstrated that treatment with Qulipta 60 mg once daily (QD) and 30 mg daily (BID) resulted in statistically significant improvements in all six secondary endpoints. This includes a key secondary endpoint that measured the proportion of patients that achieved at least a 50 percent reduction in mean monthly migraine days across the 12-week treatment period.
|Josh Slatko is contributing editor of Med Ad News and PharmaLive.com.|
Over the top
The biopharma industry’s response to the global pandemic has propelled some COVID-19 vaccines into the leading ranks of the world’s best-selling products,…
Over the top
The biopharma industry’s response to the global pandemic has propelled some COVID-19 vaccines into the leading ranks of the world’s best-selling products, with Pfizer/BioNTech’s Comirnaty surpassing AbbVie’s Humira for the No. 1 spot.
By Andrew Humphreys • email@example.com
The ripple effects of the worldwide COVID-19 pandemic continue to be felt throughout the biopharmaceutical realm, from allocation of business resources to the revenue impact of new vaccines and treatments for the industry’s main players. No biopharma company has thrived more during the pandemic’s reign than Pfizer, which experienced the largest increase in market capitalization during 2021 at $127 billion, rising to $331 billion.
Pfizer has collaborated with BioNTech to jointly develop the mRNA-based coronavirus vaccine Comirnaty/BNT162b2 to help prevent COVID-19. Comirnaty/BNT162b2 accounted for 45 percent of Pfizer’s total revenue during 2021, coming in at $36.78 billion. For the first six months of 2022, Pfizer reported Comirnaty direct sales and alliance revenue of $22.08 billion. As of July 28, Pfizer forecasted $32 billion in revenue for Comirnaty for full-year 2022, with gross profit to be split evenly with BioNTech, which includes doses expected to be delivered throughout the fiscal year.
Comirnaty is based on BioNTech’s proprietary messenger RNA technology. As the first-ever approved mRNA therapy, Comirnaty additionally represents BioNTech’s first commercial product. Through the vaccine, BioNTech’s revenue grew from €482.3 million ($571 million) in 2020 to €18.98 billion ($22.45 billion) for 2021. In reporting first-quarter 2022 results, BioNTech reiterated the company’s prior full-year 2022 financial year outlook of €13 billion ($15.4 billion) to €17 billion ($20.11 billion).
Pfizer-BioNTech’s COVID-19 vaccine is authorized by the U.S. Food and Drug Administration under Emergency Use Authorization (EUA) for active immunization to prevent coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals 6 months of age and older. Comirnaty (approved under a Biologics License Application)/BNT162b2 (authorized under EUA) in July 2022 became the first COVID-19 vaccine to be granted FDA approval for adolescents 12 years and older, following U.S. emergency use authorization in May 2021. Comirnaty became the first FDA-approved COVID-19 vaccine for individuals 16 years and older during August 2021.
The impact of the worldwide pandemic led to the unseating of Humira (adalimumab) as the world’s top-selling pharmaceutical product in 2021, which was the medicine’s best-performing year ever. Humira has annually been the best seller among prescription medicines dating back to 2012. The drug’s combined revenue for 2021 between AbbVie and Japan’s Eisai topped $21.18 billion. AbbVie reported $20.69 billion of that total, the first time Humira broke the $20 billion barrier in one year for the North Chicago-based company. For first-half 2022, AbbVie reported Humira worldwide revenue of $10.1 billion.
Humira is administered as a subcutaneous injection. The biologic therapy is approved for treating various autoimmune diseases in North America and in the European Union: rheumatoid arthritis (moderate to severe), psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease (moderate to severe), plaque psoriasis (moderate to severe chronic), juvenile idiopathic arthritis (moderate to severe polyarticular), ulcerative colitis (moderate to severe), axial spondyloarthropathy, pediatric Crohn’s disease (moderate to severe), hidradenitis suppurativa (moderate to severe), pediatric enthesitis-related arthritis, non-infectious intermediate, posterior and panuveitis, pediatric ulcerative colitis (moderate to severe), and pediatric uveitis. Humira is approved in Japan for treating intestinal Behçet’s disease and pyoderma gangrenosum.
Humira is sold in other markets around the globe, including Japan, China, Brazil, and Australia. The medication accounted for 37 percent of AbbVie’s total net revenue during 2021 and nearly 36 percent during the first six months of 2022.
Moderna’s COVID-19 vaccine Spikevax (mRNA-1273) has been authorized for use or approved in more than 70 countries. The FDA fully approved the BLA for Spikevax for individuals 18 years of age and older in January 2022. Moderna’s COVID-19 vaccine was made available under EUA in the United States on Dec. 18, 2020. The full licensure of Spikevax in the United States joined that in Canada, Japan, the European Union, the UK, Israel, and other countries where the adolescent indication is additionally approved.
During June 2022, Moderna gained EUA from the FDA for the company’s COVID-19 vaccine mRNA-1273 in young children ages 6 months through 5 years of age at a dose level of 25 µg. Moderna has additionally received emergency use authorization for a 50 µg two-dose regimen of mRNA-1273 for children ages 6 through 11 years old and a 100 µg two-dose regimen for adolescents aged 12 through 17 years old.
Spikevax marks Moderna’s first commercial product. Sales amounted to nearly $17.68 billion during full-year 2021. For the first six months of 2022, Moderna reported product sales of about $10.46 billion.
Keytruda ranks as the world’s top-selling cancer therapeutic. Global sales for Merck’s checkpoint inhibitor grew from $11.08 billion during 2019 to $14.38 billion for 2020 and $17.19 billion in 2021. For first-half 2022, Merck reported Keytruda global sales of $10.06 billion. The anti-PD-1 (programmed death receptor-1) therapy contains the active chemical pembrolizumab.
Keytruda works by increasing the ability of the body’s immune system to help detect and fight tumor cells. The humanized monoclonal antibody blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes that may affect both tumor cells and healthy cells.
Outside the COVID-19 vaccine domain, Keytruda is expected to overtake Humira as the top-selling prescription medicine in 2023 when the latter’s U.S. market exclusivity is set to expire. AbbVie has entered into settlement and license deals with several adalimumab biosimilar manufacturers. The licenses in the United States will start during 2023 and the licenses in Europe began in 2018. “The inevitable arrival of Humira biosimilars in the U.S. next year means that AbbVie is hurtling towards biopharma’s biggest-ever patent cliff,” according to Evaluate Pharma analysis.
Meanwhile, Keytruda is anticipated to continue thriving as the product’s compound patent is protected from expiration in all majors markets until at least 2028 (the United States and China) and into the following decade in the EU and Japan.
According to analysts from Evaluate Pharma, come 2028, Keytruda will remain the top-selling non-Covid treatment with estimated sales of $30.9 billion. By that year, the top-selling pharmaceutical of all-time, Humira, will no longer be a member of the top 10 sellers (see graphic on this page).
Per Evaluate Pharma, the No. 2 seller in 2028 is projected to be Bristol Myers Squibb and Ono Pharmaceutical’s Opdivo (nivolumab), predicted to trail Keytruda by nearly half in revenue at $15.7 billion. A fully human monoclonal antibody that binds to the PD-1 on T and NKT cells, the biological product Opdivo has received approvals for various anti-cancer indications including bladder, blood, colon, head and neck, kidney, liver, lung, melanoma, mesothelioma and stomach.
Download the listing of the top 200 medicines based on global sales during 2021.
Andrew Humphreys is contributing editor of Med Ad News and PharmaLive.com.emergency use authorization pandemic coronavirus covid-19 vaccine treatment fda medication therapy rna brazil japan canada european europe uk eu china
Braxia and KetaMD, CEOs McIntyre and Gumpel Speak on Acquisition
Last week, the Canadian company Braxia Scientific acquired 100% of the issued and outstanding stock of KetaMD, Inc. This is an exciting acquisition, and…
Last week, the Canadian company Braxia Scientific acquired 100% of the issued and outstanding stock of KetaMD, Inc. This is an exciting acquisition, and in today’s interview, The Dales Report’s Nicole Hodges talks with CEOs Dr. Roger McIntyre and Warren Gumpel of Braxia Scientific and KetaMD respectively.
For some background information, KetaMD is a U.S. based, privately-held, innovative telemedicine company, with a mission to address mental health challenges via access to technology-facilitated ketamine-based treatments. Braxia Scientific is Canada’s first clinic specializing in ketamine treatments for mood disorders. They recorded revenue of $1.49m for 2022 fiscal year, ended March 31. On a year-over-year basis, revenue increased 47.5%.
Here’s some highlights from the interview.
KetaMD gives Braxia a presence in the US
Dr. McIntyre says that KetaMD gives Braxia what they’ve had as their vision from the beginning: a US presence. KetaMD is a living program. It’s already running, has infrastructure, and patients. McIntyre believes that a program like KetaMD is something Braxia’s needed to scale and obtain commercial success.
With telemedicine, Braxia has a potential to serve a gap in access. The zeitgeist of “patient going to medicine” has flipped, McIntyre says. “Now it’s medicine goes to the patient, and that is long overdue.”
COVID speeding a trend that was already happening
In 2020, 80% of physicians indicated they had virtual visits. That’s a number up from 22% the year before. But this is something that many doctors, McIntyre included, believe always should have happened. The pandemic only was the catalyst for innovation and making the option viable.
While some treatments will always need a clinic or a hospital, McIntyre believes some treatments can be done safely at home. And they are, for many chronic diseases. He feels implementing ketamine and psychedelics would be among these treatments where service could be expanded into the home. It would require careful SOPs in place, best practices, and surveillance. But he believes Braxia Scientific could deliver this with KetaMD.
Gumpel to stay as CEO of KetaMD
Gumpel says that KetaMD benefits in this acquisition from being part of the world’s most prominent researchers in depression, psychedelics, and ketamine. In the acquisition, he’ll stay on as CEO. He admits that Dr. McIntyre has been a huge part of collecting the data on the safety of ketamine treatment, and has a strong motivation to “see this thing through until most of society can access that – or at least the people that need it and want it.”
Gumpel admits he has a personal connection to ketamine treatment. As a person who has experienced bouts of depression for years, it saved his life, he says. He is grateful he was living within walking distance of ketamine treatment in Manhattan. It made him extremely aware of the accessibility gap, which in part inspired KetaMD.
Be sure to tune in for the full interview regarding Braxia and KetaMD, right here on The Dales Report!
The post Braxia and KetaMD, CEOs McIntyre and Gumpel Speak on Acquisition appeared first on The Dales Report.depression pandemic treatment canada
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