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Monday, August 23, 2021

FDA issues warning on robot-assisted breast cancer surgery

 The FDA has issued a safety alert about the use of robot-assisted surgical (RAS) devices for use in mastectomy procedures, pointing out that their safety and efficacy have not been established.

The move comes amid reports that some people are being offered RAS for the prevention or treatment of breast cancer, sometimes as part of a clinical trial, even though many of the studies are being undertaken “without the FDA oversight required”.

RAS devices – which enable surgeons to use computer software and mechanical arms to carry out procedures whilst viewing the site on video – have been cleared for use in some types of surgery commonly performed in patients with cancer, such as hysterectomy, prostatectomy and colectomy.

The agency says however that it hasn’t been able to review any evidence that could support the use of robotic surgery for cancer prevention or treatment, such as studies that look at hard clinical outcomes data like “overall survival, recurrence, and disease-free survival”.

The announcement follows a Medscape report a few weeks ago that clinical trials are underway using RAS devices for nipple-sparing mastectomy, both prophylactically and as a breast cancer treatment, that were not collecting outcomes data despite warnings by the FDA.

“The FDA continues to expect study sponsors to obtain FDA approval of investigational device exemptions (IDE) for studies of RAS devices intended for use in mastectomy procedures for the prevention or treatment of breast cancer,” said the regulator in its alert.

Only with those approvals can clinical trial participants be certain that they have “adequate protections of the health, safety, and welfare”, it added.

Other uses of RAS devices have typically been approved on the back of 30-day follow-up studies, but the regulator wants to hold the devices to a higher standard where there is a claim on cancer prevention or treatment.

In 2019, the FDA said that the use RAS devices for mastectomies and other cancer surgeries was unproven, and could pose safety risks for patients as well as reducing their chances of a good clinical result.

At the time, it cited a study which found that the use of RAS devices to perform radical hysterectomies in women with cervical cancer was associated with lower rates of overall survival than traditional surgical techniques.

Use of RAS is on the increase because they can allow surgeries to be performed through a smaller incision, reducing scarring, post-operative pain and blood loss, and potentially reducing recovery times.

The FDA said device manufacturers, investigators, clinical study sponsors and institutional review boards (IRBs) need to be aware of its expectations for IDE and clinical endpoints for use of RAS devices for the prevention or treatment of patients with cancer.

https://pharmaphorum.com/news/fda-issues-warning-on-robot-assisted-breast-cancer-surgery/

Trillium gets a buyout while it's down

 In hindsight, the clues were there: Pfizer’s $25m equity investment in Trillium Therapeutics last year left the big pharma as the only real suitor for the CD47 specialist. And, with Pfizer rolling in Covid-19 vaccine cash and with a need for deals, it made sense to pull the trigger now.

Another reason behind the timing of today’s takeover could be Trillium’s valuation, which is not what it was in late 2020. Even with a 200% premium over Trillium’s closing share price on Friday, at $2.26bn Pfizer is getting the group for less than it was worth last November – and notably it is paying a lot less than the $4.9bn Gilead shelled out for Trillium's competitor Forty Seven last year.  

With several anti-CD47 targets now in the hands of big players, investors are no doubt asking themselves who might be next on the auction block. A look at the table below shows plenty of contenders out there.

Best in class?

Trillium has two shots at CD47 with TTI-621 and TTI-622. Both are anti-SIRPα-Fc fusion proteins, the former an IgG1 and the latter IgG4. Trillium argues that these are the only molecules targeting the SIRPα-CD47 axis that have so far shown clinically meaningful monotherapy responses.

Today, Pfizer and Trillium disclosed a 30% overall response rate among 30 patients in a phase 1 trial of TTI-622, including two complete responses, at a cut-off date of July 26.

However, the recent pivot to combination trials had dented investor confidence about the projects’ monotherapy promise, Evercore ISI’s Josh Schimmer noted. These worries have obviously not put off Pfizer, however, which acknowledged during a call today that Trillium’s projects might not be first in class, but that they have the potential to be best in class.

Executives highlighted data pointing to lower anaemia risk and possibly the potential for the Trillium assets to be dosed lower; both projects also promote a pro-phagocytic signal – or the “eat me” signal – by engaging the activating receptor FcγR on macrophages. Pfizer is targeting regulatory approvals from 2025, they added.

First in class

Gilead’s magrolimab, gained through the Forty Seven purchase, is some way ahead. In myelodysplastic syndrome the group hopes to file for accelerated approval on a phase 1b combo trial with azacitidine, results from which are due later this year.

In front-line acute myeloid leukaemia, meanwhile, Gilead recently started a phase 3 trial of magrolimab plus azacitidine, called Enhance-2.

Another late-stage contender is ALX Oncology’s evorpacept, whose shares climbed 20% today, perhaps on hopes that it could also be a takeout target.

The group will soon start a phase 2/3 trial of the asset in combo with Herceptin in Her2-positive gastric or gastroesophageal junction cancer, Aspen-06. Data in the same setting, from the phase 1 Aspen-01 trial, are set to be presented at next month’s Esmo meeting, which could give clues on this project’s future here.

ALX is also testing evorpacept in combination with Keytruda in head and neck cancer.

Pfizer itself has another CD47-targeting asset in development: a bispecific antibody that also hits PD-L1. However, this is very early in development, with a phase 1 study yet to start recruiting. Whether Pfizer will have to divest this asset to satisfy antitrust regulators is an open question.

Whether other big names now also decide to buy into CD47 or not, Pfizer’s purchase of Trillium is validation of a strategy that looked dead and buried after Celgene discontinued CC-90002 and Surface Oncology quietly shelved SRF231 (Trillium punishes its investors, February 22, 2019). What a difference two years can make in biopharma.

Anti-CD47s in the clinic
ProjectCompany (originator)
Description
Trial ID 
Phase 3
MagrolimabGilead Sciences (Forty Seven)Anti-CD47 antibodyEnhance (NCT04313881) in MSD; Enhance-2 (NCT04778397) in AML
Phase 2/3
ALX148ALX OncologyAnti-CD47/SIRPα fusion protein Ph2/3 Aspen-06 in gastric (NCT05002127); ph2/3 Aspen-03 (NCT04675294) & Aspen-04 in H&N (NCT04675333) 
Phase 1/2
AO-176Arch OncologyAnti-CD47 antibodyPh1/2 in solid tumours (NCT03834948) & multiple myeloma (NCT04445701)
Lemzoparlimab (TJC4)Abbvie (I-Mab)Anti-CD47 antibodyPh1/2 in AML/MDS (NCT04202003) & ph1 solid tumours/lymphoma (NCT03934814)
DSP107Kahr MedicalCD47x41BB fusion proteinPh1/2 in solid tumours (NCT04440735) & AML/MDS/CML (NCT04937166)
IBI188Innovent BiologicsAnti-CD47 antibodyPh1/2 China study in AML (NCT04485052)
TTI-621Trillium TherapeuticsAnti-CD47/SIRPα fusion protein Ph1/2 in leiomyosarcoma (NCT04996004); ph1 in haem malignancies/soild tumours (NCT02663518)
Phase 1
TTI-622Trillium TherapeuticsAnti-CD47/SIRPα fusion protein Ph1 in haem malignancies (NCT03530683)
TG-1801TG Therapeutics (Light Chain Bioscience)Anti-CD19-CD47 bispecific Ph1 in B-cell lymphoma (NCT03804996) & B-cell lymphoma/CLL (NCT04806035)
IMC-002Sorrento Therapeutics (Immuneoncia Therapeutics)Anti-CD47 antibodyPh1 in solid tumours/lymphoma (NCT04306224)
STI -6643Sorrento TherapeuticsAnti-CD47 antibodyPh1 in solid tumours (NCT04900519)
GS-0189 (FSI-189)Gilead Sciences (Forty Seven)Anti-SIRPα antibodyPh1 in NHL (NCT04502706)
SL-172154Shattuck LabsBi-functional fusion protein targeting CD47 and CD40Ph1 in ovarian cancer (NCT04406623) & skin/H&N cancers (NCT04502888)
CC-95251Bristol-Myers Squibb (Celgene) Anti-SIRPα MabPh1 in haem cancers/solid tumours (NCT03783403)
Effi-dem (BI 765063/OSE-172)Boehringer Ingelheim/OSE Immunotherapeutics (Effimune)Monoclonal antibody SIRPα antagonistPh1 in solid tumours in Europe (NCT03990233) & Japan (NCT04653142)
IBI322Innovent BiologicsAnti-CD47/PD-L1 bispecific antibodyPh1 in solid tumours (NCT04328831) & haem cancers (NCT04795128, both China only)
ZL-1201Zai LabAnti-CD47 antibodyPh1 in advanced cancers (NCT04257617)
PF-07257876PfizerCD47xPD-L1 bispecificPh1 in solid tumours (NCT04881045)
IMM0306Immuneonco BiopharmaceuticalsCD47xCD20 bispecificPh1 in B-NHL (NCT04746131)
IMM01Immuneonco BiopharmaceuticalsAnti-CD47 antibodyPh1 China trial in lymphoma (ChiCTR1900024904)
Source: Evaluate Pharma & clinicaltrials.gov.

https://www.evaluate.com/vantage/articles/news/deals/trillium-gets-buyout-while-its-down

Delta variant, having put kibosh on Fed event, begins to menace recovery

 

The resurgence of the COVID-19 pandemic dealt its most visible blow yet as Federal Reserve officials abruptly cancelled their premier in-person conference, raising questions about their insistence the economy faces limited risk from the Delta strain and plans to dial back crisis-era support.

The setback, announced late Friday, with the annual Jackson Hole, Wyoming, symposium now virtual for the second straight year, is the latest in a series of small but accumulating signs the new surge is having more of an impact than Fed officials anticipated. Chair Jerome Powell was already scheduled to deliver his keynote speech on Friday by webcast.

It comes at a critical time as the U.S. central bank considers when to start shrinking its extraordinary support for the economy. Most policymakers had been keen to begin reducing the Fed's asset-purchase program by the end of this year, according to the minutes of the July 27-28 policy meeting.

Until now, Powell has downplayed the impact of Delta. People and businesses had learned to "live their lives, despite COVID," he said, indicating the central bank's outlook for an improving economy remained intact despite the resurgence in cases and uneven vaccination rates.

"People and businesses have improvised and learned to adapt," Powell said in an Aug. 17 webcast event with teachers and students. U.S. economic growth surpassed pre-pandemic levels in the second quarter and is likely to be revised higher later this week.

That confidence could now be mislaid with the quickly evolving situation causing a dashboard of indicators to flash some potential warning signs.

HIGH-FREQUENCY DATA FALTERS

Nearly all of the recovery measures for individual U.S. states tracked by Oxford Economics fell for the latest week available. States in the South saw the sharpest drops, led by Louisiana, Florida, and Mississippi.

"Greater consumer caution weakened demand and mobility, which fell to multiweek lows. Employment soured, production retrenched, and the health tracker fell on surging Delta variant contagion," Oxford's team of U.S. economists wrote.

COVID-19 deaths in the United States reached a five-month high last week as the more contagious Delta variant runs rampant in areas with low vaccination rates. Cases continue to rise and the United States, as of Friday, was averaging about 139,000 new infections each day.

Small business hiring tracked by time management company Homebase has edged down, while Bank of America credit and debit card data showed a decline in spending on leisure in the last seven days. Restaurant bookings through OpenTable have also fallen in recent days.

U.S. consumer sentiment also dropped sharply in early August, hitting its lowest level in a decade, with more negative outlooks on everything from personal finances to inflation and employment, a University of Michigan survey showed.

"We have made all the easy wins of reopening, and the plain fact is the virus is catching up with us. So there is some cooling ... economists got a little over-enthusiastic," said Vincent Reinhart, a former Fed staffer who is chief economist at BNY Mellon Asset Management.

On Wednesday, Goldman Sachs economists lowered their forecast for third-quarter economic growth to 5.5% from 9%, citing the Delta variant's prolonged impact, although they revised up their estimates for the fourth quarter and most of next year.

Others caution not to read too much into the softening after a surge in economic activity amid the reopening and pent-up demand being released over the summer. "So far, real-world impacts have been relatively small and localized," said Jefferies in its analysis of real-time data, noting declines in restaurant bookings had been led by states with large COVID-19 outbreaks, such as Florida and Texas.

There does, however, appear to be a growing crisis of confidence among some major employers, many of whose offices have been half-empty for more than 18 months. On Thursday, Apple Inc delayed the return to its corporate offices to January at the earliest.

Dallas Fed President Robert Kaplan, one of the central bank's most forceful supporters for reducing support for the economy, said on Friday the impact of the Delta variant was "unfolding rapidly" and that he may adjust his views on monetary policy "somewhat" should it slow economic growth materially. Kaplan has previously said he would like the Fed to begin tapering its asset purchases in October.

SUPPLY-CHAIN ISSUES

Fed policymakers are also keenly watching the handful of categories that have contributed to an outsized jump in inflation due to supply-chain bottlenecks, as well as any signs price pressures may be broadening.

Many at the Fed, including Powell, maintain that current high inflation readings are temporary and will ebb back towards the central bank's 2% average goal, but some policymakers are growing more anxious.

U.S. consumer price increases slowed in July even as they remained at a 13-year high on an annual basis, and there were tentative signs inflation has peaked. The surge fueled by the Delta variant is pressuring that premise.

China's 'zero tolerance' COVID-19 policy saw a terminal at its second-largest container port by handling volume temporarily shut down last week due to an outbreak, and several other Chinese ports faced further congestion as vessels were diverted and cargo processing slowed due to stricter disinfection measures.

Leading international shipping groups warned clients of delays and route adjustments as global supply chains came under further strain, which could keep price pressures elevated in the United States for a range of parts and goods.

The months-long shortage of global semiconductors that has pushed up prices of new and used vehicles shows no signs of abating as the Delta variant spreads across Asian countries that are home to auto factories and chip plants.

Toyota, the world's largest automaker by sales volumes, said on Thursday it would slash its planned global production for September by 40%, a move that impacts most of its North American factories.

Should U.S. supply issues, including a shortage of labor, persist even as vaccinations, boosters, better treatments and healthy savings keep demand from cratering, the chances of a blunder by the Fed goes up if it is forced to quickly raise interest rates to keep a lid on inflation, said Diane Swonk, chief economist at Grant Thornton.

"What many once hoped would be a sprint has become a marathon of a pandemic with the finish line a mirage," Swonk said. "The risk of a policy misstep and a premature end to this business cycle is rising."

https://www.marketscreener.com/news/latest/Delta-variant-having-put-kibosh-on-Fed-event-begins-to-menace-recovery--36224549/

Xeris Gets FDA OK on Application for Treatment of Severe Hypoglycemia

 First ready-to-use liquid glucagon available in a single-dose vial and syringe kit for rescue

Gvoke HypoPen®, Gvoke® PFS, and Gvoke® Kit – three different administration options to accommodate patients’ preferences

Gvoke Kit eliminates the need for reconstitution

Gvoke Kit availability anticipated in early Q1 2022

https://finance.yahoo.com/news/xeris-pharmaceuticals-announces-approval-supplemental-120000266.html

Pfizer’s COVID-19 vaccine gets full FDA approval

 The Food and Drug Administration granted full approval to the Pfizer / BioNTech COVID-19 vaccine, another landmark in the historic immunization campaign. The vaccine was previously available to people over the age of 12 in the United States under an emergency use authorization. Now, it’s officially licensed in the United States.

With full approval, Pfizer and BioNTech can directly market the shot to consumers. The vaccine will be marketed under the name Comirnaty to people over 16. It will still be available to people 12-15 years old under an emergency use authorization.

“The FDA’s approval of this vaccine is a milestone as we continue to battle the COVID-19 pandemic,” acting FDA Commissioner Janet Woodcock said in a statement. “While this and other vaccines have met the FDA’s rigorous, scientific standards for emergency use authorization, as the first FDA-approved COVID-19 vaccine, the public can be very confident that this vaccine meets the high standards for safety, effectiveness, and manufacturing quality the FDA requires of an approved product.”

The approval may also push more companies and schools to mandate vaccinations. While it’s legal for them to require vaccinations under an emergency authorization, some have been reluctant to do so.

The companies needed to provide six months of safety and efficacy data on their vaccine to the FDA in order to submit their application for what’s called a Biological License. The agency only asked companies to collect two months of data before applying for an emergency use authorization. The shortened timeline allowed the agency to sidestep some of the more lengthy regulatory steps and get vaccines to people quickly during the crisis.

FDA approval may help some people who were on the fence about getting vaccinated feel more comfortable taking the shot. One May survey found that one-third of unvaccinated adults would be more likely to get a COVID-19 vaccine that was fully approved.

Now that one COVID-19 vaccine has full approval, other pharmaceutical companies will not be able to ask the FDA for new emergency use authorizations. Emergency authorizations can only be issued for drugs or vaccines when there are no approved options available — now that the Pfizer / BioNTech shot is licensed, that’s no longer the case. If AstraZeneca, for example, wanted to make its shot available in the US, it would have to start with the longer formal approval process.

https://www.theverge.com/2021/8/23/22616546/pfizer-covid-vaccine-fda-approval-licensing

Vivos gets FDA market clearance for oral sleep apnea device

 Part of the Vivos System Treatment, the mmRNA Device Represents a Highly Effective Non-Surgical, Non-Invasive and Non-Pharmaceutical Alternative for Patients Suffering from OSA

Approval Expands Insurance Reimbursement Potential, Including the Opportunity for Medicare Coverage for mmRNA

HIGHLANDS RANCH, Colo., Aug. 23, 2021 (GLOBE NEWSWIRE) -- Vivos Therapeutics, Inc. (the “Company” or “Vivos”) (NASDAQ: VVOS), a medical technology company focused on developing and commercializing innovative diagnostic and treatment modalities for patients suffering from sleep-disordered breathing, including mild to moderate obstructive sleep apnea (OSA), today announced the U.S. Food and Drug Administration (FDA) has granted 510(k) market clearance to Vivos’ mmRNA (modified mandibular Repositioning Nighttime Appliance) device for treating mild to moderate OSA, sleep-disordered breathing and snoring in adults. This FDA clearance paves the way for expanded insurance reimbursement coverage for the mmRNA device, including Medicare, as well as for potential future government contracts and reimbursement from commercial payers that follow Medicare guidelines.

https://finance.yahoo.com/news/fda-grants-510-k-market-113000440.html

Pfizer to buy cancer drug developer Trillium in $2.3 bln deal

 Pfizer Inc said on Monday it would buy Canadian drug developer Trillium Therapeutics Inc in a $2.26 billion deal to strengthen its arsenal of blood cancer therapies.

Pfizer, which acquired a $25 million stake in Trillium last year, will buy the remaining outstanding shares for $18.50 apiece, representing a 203.8% premium on the stock's last closing price.

Pfizer expects to benefit from Canada-based Trillium's blood-cancer therapies that target a "don't eat me" signal used by cancer cells to evade the immune system.

Forty Seven Inc, which is also developing drugs that target the same antibodies, was bought by Gilead Sciences Inc for $4.9 billion last year.

More than 1 million people worldwide were diagnosed with blood cancer in 2020, representing almost 6% of all cancer diagnoses. The same year, more than 700,000 people worldwide died from a form of blood cancer.

Trillium's U.S.-listed shares were trading at $17.73 before the bell on Monday, having fallen 59% in 2021 as of their last close. Pfizer bought nearly 2.3 million Trillium shares at $10.88 each in September.

Pfizer's financial adviser for the transaction is BofA Securities Inc, and Centerview Partners LLC is Trillium's. 

https://finance.yahoo.com/news/1-pfizer-buy-trillium-therapeutics-110909091.html