1st patient treated with Flash radiation therapy in clinical trial

 Flash radiation therapy was used to treat the first patient in the world earlier this week during the start of a clinical trial at the Proton Therapy Center at Cincinnati Children's Hospital, according to a Nov. 19 news release.

Flash radiation therapy delivers ultra-high doses in less than one second, up to 100 times faster than the traditional method, and can eliminate the debilitating side effects. 

The clinical trial is expected to enroll up to 10 patients with bone metastases and will test the use of Varian Medical System's ProBeam, a proton therapy system that enables ultra-high dose rates. 

Researchers completed several years of studies on Flash therapy before starting the clinical trial. 

"The prior three years of preparation by the researchers, engineers, clinical and physics teams culminated in a treatment that was completed in literally a blink of the eye, and the patient was discharged feeling well," John Breneman, MD, principal investigator, told Becker's.

While more research needs to be done, existing findings suggest that very few sessions of Flash therapy would be needed — between one and five, Agam Sharda, senior director of the Flash program at Varian, said in an email to Becker's. 

The clinical trial aims to evaluate clinical workflow feasibility, potential side effects and efficacy of the treatment, which will be measured by participant pain relief. 

https://www.beckershospitalreview.com/oncology/first-patient-treated-with-flash-radiation-therapy-in-clinical-trial.html

S&P turns broadly positive as Schumer says stimulus talks back on

 

• A good, old-fashioned fiscal stimulus headline is enough to spark some buying in a market that was drifting for most of the session.
• Senate Minority Leader Chuck Schumer says Senate Majority Leader Mitch McConnell is ready to resume talks. Staffs are "going to sit down today or tomorrow to try to begin to see if we can get a real good Covid relief bill", Schumer says.
• The S&P (SP500) +0.3% was slightly higher, then rallied as the headline hit. Nine of 11 sectors are in the green, with Energy (NYSEARCA:XLE) racing to the lead. Crude futures +0.1% popped about 40 cents.
• https://seekingalpha.com/news/3638072-s-and-p-turns-broadly-positive-schumer-says-stimulus-talks-back-on

Breast cancer biotech Olema Pharmaceuticals prices upsized IPO above range at $19

 Olema Pharmaceuticals, a Phase 1 biotech developing a targeted oral therapy for ER+/HER2- breast cancer, raised $209 million by offering 11 million shares at $19, above the range of $16 to $18. The company offered 1 million more shares than anticipated. At pricing, the company raised 23% more in proceeds than anticipated.

Olema Pharmaceuticals plans to list on the Nasdaq under the symbol OLMA. J.P. Morgan, Jefferies, Cowen and Canaccord Genuity acted as lead managers on the deal.

Relevant Profile: OLMA

https://www.renaissancecapital.com/IPO-Center/News/73289/Breast-cancer-biotech-Olema-Pharmaceuticals-prices-upsized-IPO-above-the-ra

Data sets up 2021 filings for Gilead’s twice-a-year HIV drug lenacapavir

 Gilead Sciences has the data it was hoping for in a pivotal trial of lenacapavir, an HIV drug that only needs to be dosed by subcutaneous injection every six months, keeping it on course for regulatory filings next year.

Lenacapavir (previously GS-6207) is the first in a new class of class HIV-1 capsid inhibitor that Gilead is hoping will eventually free patients from the need to take daily oral tablets, although initially it is being developed for patients who are failing their current treatment regimen.

The drug is also a key part of Gilead’s plans to defend its $16 billion HIV franchise from rivals which are also developing long-acting injectables, namely ViiV Healthcare with cabotegravir and Merck & Co’s islatravir (MK-8591).

The 36-patient CAPELLA trial tested lenacapavir in highly treatment-experienced HIV patients who had developed resistant to their current drugs, with virus levels rising as a result.

It found that 21 of 24 (88%) of patients on the capsid inhibitor experienced a 0.5 log10 reduction in viral load after 14 days, compared to two of 12 patients (17%) on placebo.

“We look forward to sharing data from longer-term follow-up of CAPELLA study participants next year and submitting these data for regulatory approval,” said the company’s head of virology Diana Brainard.

The FDA granted breakthrough designation to lenacapavir for the treatment of resistant HIV, which has become a niche part of the overall HIV market thanks to much-improved oral drug regimens in recent years.

In time, Gilead wants in time to extend the use of lenacapavir into additional and much larger indications, including the general HIV-positive population as well as for pre-exposure prophylaxis (PrEP) among people who have sex with HIV-positive partners.

Earlier this year Gilead added a lenacapavir arm to its planned prevention study in women at risk of HIV – which is being carried out to expand the label for Descovy after it was approved with a narrower PrEP indication than Truvada last year.

In parallel, Gilead is also planning to carry out a study of lenacapavir for HIV prevention in men and transgender people who have sex with men.

PrEP is already a big market for HIV drugs like its blockbuster brands Descovy (emtricitabine/tenofovir alafenamide) and Truvada (emtricitabine/tenofovir disoproxil fumarate), which accounted for around $1.5 billion and $3 billion of Gilead’s HIV sales last year.

Descovy’s approved indication excluded people who have receptive vaginal intercourse due to a lack of efficacy data in that population, and Gilead wants to shore up the label quickly as Truvada is facing the loss of patent protection. It is thought that around two-thirds of Truvada’s near-$3 billion in 2019 sales came from use as PrEP.

Expanding the use of lenacapavir into the broader population could be complex however as Gilead will need to find another long-acting drug that can be partnered with it to reduce the risk of resistance to the capsid inhibitor.

https://pharmaphorum.com/news/data-sets-up-2021-filings-for-gileads-twice-a-year-hiv-drug-lenacapavir/

Feds lay out ambitious timeline for Covid vax distribution

 With Moderna and Pfizer both reporting sky-high response rates to their COVID-19 vaccines, the pressure is on federal health officials to ensure a rapid—but  smooth—rollout. Wednesday, they unveiled a detailed timeline that provides some clues about when most Americans can expect to be vaccinated.

High-priority populations such as healthcare workers and nursing home residents could obtain COVID-19 vaccines in December, Department of Health and Human Services Secretary Alex Azar said in a press conference. Anthony Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases, predicted in a meeting with USA Today’s editorial board that everyday Americans could be vaccinated as early as April.

Azar and Fauci were clearly encouraged by the flood of good news from Pfizer, its vaccine partner BioNTech and Moderna. It started Monday, when Moderna said its mRNA COVID-19 vaccine was 94.5% effective in a phase 3 trial. Then Pfizer updated its previous report of 90% efficacy, saying yesterday that its vaccine was 95% effective in a phase 3 trial. Pfizer expects to seek emergency use authorization from the FDA presently.

The key to distributing the vaccines to older Americans quickly is a distribution deal the government struck with Walgreens and CVS last month. Last week, more agreements were formed with pharmacy chains and independent pharmacies, Azar said.  

"We have seen tremendous uptake of that option already,” Azar said yesterday. “Ninety-nine percent of skilled nursing facilities across the country have signed up, and 100% of facilities in 20 states are signed up.” Forty million vaccine doses will be available in the U.S. by the end of this year, he added.

Azar has said in several media appearances that all healthcare workers and first responders should be able to access COVID-19 vaccines by the end of January.

But meeting that goal, and providing widespread vaccination by April, will hinge on Pfizer and Moderna avoiding delays that are all too common in the FDA review process. Moncef Slaoui, Ph.D., co-leader of the U.S. government’s Operation Warp Speed program, warned in an interview with Fierce Pharma last month that “an approval is going to take several weeks from the moment one says, ‘OK, the vaccine is efficacious.'"

Warp Speed has been fostering the development of six additional COVID-19 vaccines, but it’s clear Pfizer and Moderna’s mRNA vaccines will be the first out of the gate. Moderna expects to ship 20 million doses for use in the U.S. by the end of this year and up to 1 billion worldwide next year. Pfizer is gearing up to ship 50 million doses this year.

The distribution of COVID-19 shots could raise a whole new set of hurdles. Both mRNA front-runners require ultra-cold storage and stringent temperature control to remain potent. That has sent airlines, shipping companies and cargo carriers on a scramble to prepare for the massive vaccination rollout.

https://www.fiercepharma.com/pharma/when-will-covid-vaccines-be-widely-available-feds-lay-out-ambitious-timeline

The wait for Astrazeneca’s pivotal Covid-19 vaccine data

 New phase II immunogenicity data with Astrazeneca’s Covid-19 vaccine candidate AZD1222 suggest that the project might work as well in older adults as it does in younger people. But these are not the data that investors are looking for; efficacy results from Astra’s phase III trials in the UK and Brazil have not yet emerged, despite hopes among some analysts that these might be reported in mid-November.

While Astra’s chief financial officer told an investor meeting this week that the phase III results were “imminent”, there were hints this morning from Astra’s partner, the University of Oxford, that readout from the UK study had been delayed by falling numbers of Covid-19 cases over the summer.

The data before Christmas?

Some analysts, including Jefferies, had hoped to see pivotal data by mid-November, basing their assumptions around infection rates and the UK study’s statistical analysis plans.

But the official line from Astra has long been that data are coming by the end of the year. Astra’s chief executive, Pascal Soriot, downplayed expectations of a November readout during the group’s third-quarter earnings call on November 5. 

And in an interview with UK BBC Radio 4 today, Professor Andrew Pollard, head of the Oxford Vaccine Group and an investigator in the UK phase II/III COV002 trial, struck a cautious tone. While he said the unblinding of that study would “definitely” take place before Christmas, he added: “We’re not quite there because of the great success we’ve had controlling the pandemic over the summer months.”

This meant “very few cases” of Covid-19 in the trial, which “really slowed things down”, he said. However, the situation has changed in the past month or so, with cases on the rise again in the UK. Professor Pollard said this made him more confident of getting the data soon.

In an unfortunate twist for Astra, readout of its rivals’ pivotal Covid-19 vaccine trials had been hastened by surging cases in the US.

And in the US Astra has fallen even further behind after an adverse event, thought to be transverse myelitis, forced it to put its phase III trial there on hold. This study was restarted in late October; it was quietly slipped out in Astra's third-quarter results presentation that its recruitment target had been increased from 30,000 to just over 40,000.

The delay to the US study has made the UK trial even more important. According to the latest trial protocol for the latter, the primary evidence of AZD1222’s efficacy will come from a pooled analysis of phase I/II studies in the UK and South Africa, the UK phase II/III study, and a phase III trial in Brazil.

However, it is unclear whether the FDA will allow these results to support a filing without at least some US data available – particularly after the recent strong efficacy results with Pfizer/Biontech’s BNT162b2 and Moderna’s mRNA-1273.

Selected trials of AZD1222
Country	Phase	N	Trial name	Trial ID
UK	Ph1/2	1,090	COV001	NCT04324606
UK	Ph2/3	12,390	COV002	NCT04400838
Brazil	Ph3	10,000*	COV003	NCT04536051
South Africa	Ph1/2	2,000	COV005	NCT04444674
US	Ph3	40,051*	-	NCT04516746
*Increase in trial size disclosed during Astra's third-quarter 2020 results. Source: EvaluatePharma, clinicaltrials.gov.

Still, Professor Pollard maintained that multiple vaccines would be needed to defeat Covid-19. One unique selling point for AZD1222 is its storage requirements; BNT162b2 and mRNA-1273 must be shipped at -70°C and -20°C respectively, which could cause distribution headaches particularly in lower-income nations, while Astra’s vaccine can be stored in the fridge for up to a year.

And now the UK company also has immunogenicity data suggesting a similar immune response in older people and younger adults. It was once feared that older people would fail to respond to Covid-19 vaccines – a concern as immune response declines with age – but these worries now seem to have been assuaged.

The results, published in The Lancet today, found comparable levels of neutralising antibodies in people receiving two doses of the vaccine across the three age groups studied: 18-55, 56-69, and 70 or over. T-cell responses were also similar.  

Good as they are, these data will probably not give Astra an edge over the frontrunners. mRNA-1273 has already shown similar immune responses in younger and older adults; BNT162b2’s immunogenicity data in the older population were not as strong, but the final phase III results, reported yesterday, found 94% efficacy in people aged over 65.

And Astra still has to prove that these antibody responses translate into efficacy in preventing Covid-19. The world is now waiting for its phase III data.

https://www.evaluate.com/vantage/articles/news/trial-results/wait-astrazenecas-pivotal-covid-19-vaccine-data

Thermo Fisher Scientific recommended by BofA after recent downswing

 

• Bank of America thinks the recent sell-off in Thermo Fisher Scientific (TMO -0.1%) after a wave of positive COVID-19 vaccine news doesn't make sense.
• "We continue to stress that TMO is a major beneficiary from COVID-19 therapeutics and vaccines manufacturing, and has extensive exposure via its bioprocessing segments, fill/finish capabilities, and supply chain," notes the firm.
• "As far as the view that a successful vaccine will result in sharp drop-off in COVID-19 testing, we also disagree and believe that the ongoing wave of COVID-19 across the US and Europe (and commentary from DGX and at the AMP 2020 meeting this week) illustrates that COVID-19 testing products sold by TMO are still very much in demand and will likely remain so at least through 1H21, particularly as the COVID vaccine manufacturing and distribution ramp will take time."
• BofA keeps a Buy rating and price objective of $535 in place.
• https://seekingalpha.com/news/3638046-thermo-fisher-scientific-recommended-buy-bofa-after-recent-downward-swing