[BostonCard]

Moderna reported its phase I results (via press release):

https://investors.modernatx.com/news-rel...na-vaccine

As best I can tell, they haven't been published yet, but the press release is fairly promising:

At day 43, two weeks following the second dose, at the 25 µg dose level (n=15), levels of binding antibodies were at the levels seen in convalescent sera (blood samples from people who have recovered from COVID-19) tested in the same assay. At day 43, at the 100 µg dose level (n=10), levels of binding antibodies significantly exceeded the levels seen in convalescent sera.

The fact that they saw neutralizing antibodies at levels comparable to convalescent plasma is a good sign.  On the other hand, the safety is a bit worrisome:

The sole incidence of a grade 3 adverse event in the 25 µg and 100 µg dose cohorts was a single participant at 100 µg who experienced grade 3 erythema (redness) around the injection site. To date, the most notable adverse events were seen at the 250 µg dose level, comprising three participants with grade 3 systemic symptoms, only following the second dose. All adverse events have been transient and self-resolving. No grade 4 adverse events or serious adverse events have been reported.

Grade 3 adverse events are "severe", so to see some in a small study like this is concerning.  You don't want to see grade 3 systemic symptoms in a vaccine study unless it is a very rare side effect, so to see multiple cases when only 15 patients have been enrolled in the cohort is a red flag.  Fortunately, that's only in the highest dose level, and only after the second dose, and neutralizing antibodies were seen at the lowest dose level.

They are going forward with 50 µg and 100 µg in the phase 2 trial, which makes sense.  I am worried that they will see systemic symptoms at these doses.  I anticipate it will be less frequent than with the 250 µg dose level, but again, the safety threshold for a vaccine trial has to be pretty high.  An early vaccine for COVID-19 might see a relaxed safety criteria compared to something like influenza or MMR, but it will still have to be fairly safe as it will be given to millions of otherwise healthy people.

I look forward to seeing the paper when it is published.

BC

[BostonCard]

Moderna reported its phase I results (via press release):

https://investors.modernatx.com/news-rel...na-vaccine

As best I can tell, they haven't been published yet, but the press release is fairly promising:

At day 43, two weeks following the second dose, at the 25 µg dose level (n=15), levels of binding antibodies were at the levels seen in convalescent sera (blood samples from people who have recovered from COVID-19) tested in the same assay. At day 43, at the 100 µg dose level (n=10), levels of binding antibodies significantly exceeded the levels seen in convalescent sera.

The fact that they saw neutralizing antibodies at levels comparable to convalescent plasma is a good sign.  On the other hand, the safety is a bit worrisome:

The sole incidence of a grade 3 adverse event in the 25 µg and 100 µg dose cohorts was a single participant at 100 µg who experienced grade 3 erythema (redness) around the injection site. To date, the most notable adverse events were seen at the 250 µg dose level, comprising three participants with grade 3 systemic symptoms, only following the second dose. All adverse events have been transient and self-resolving. No grade 4 adverse events or serious adverse events have been reported.

Grade 3 adverse events are "severe", so to see some in a small study like this is concerning.  You don't want to see grade 3 systemic symptoms in a vaccine study unless it is a very rare side effect, so to see multiple cases when only 15 patients have been enrolled in the cohort is a red flag.  Fortunately, that's only in the highest dose level, and only after the second dose, and neutralizing antibodies were seen at the lowest dose level.

They are going forward with 50 µg and 100 µg in the phase 2 trial, which makes sense.  I am worried that they will see systemic symptoms at these doses.  I anticipate it will be less frequent than with the 250 µg dose level, but again, the safety threshold for a vaccine trial has to be pretty high.  An early vaccine for COVID-19 might see a relaxed safety criteria compared to something like influenza or MMR, but it will still have to be fairly safe as it will be given to millions of otherwise healthy people.

I look forward to seeing the paper when it is published.

BC

[burger]

This is good news. 

I would really like to see challenge trials. If the numbers of cases continue to drop in the US, they're going to be hard-pressed to get a good sample of exposed people for Phase III.  This would also speed things up by many months.

Also, shouldn't the "warp speed" people in the federal government be clamoring to make 300 million doses of this?  The only thing we have to lose is money.  If a better candidate comes along, then at least we'll have the infrastructure in place.

[burger]

This is good news. 

I would really like to see challenge trials. If the numbers of cases continue to drop in the US, they're going to be hard-pressed to get a good sample of exposed people for Phase III.  This would also speed things up by many months.

Also, shouldn't the "warp speed" people in the federal government be clamoring to make 300 million doses of this?  The only thing we have to lose is money.  If a better candidate comes along, then at least we'll have the infrastructure in place.

[akiddoc]

Good thing I bought stock in Moderna 6 weeks ago. Bad thing is I only bought $3000.

[akiddoc]

Good thing I bought stock in Moderna 6 weeks ago. Bad thing is I only bought $3000.

[dabigv13]

This is good news. 

I would really like to see challenge trials. If the numbers of cases continue to drop in the US, they're going to be hard-pressed to get a good sample of exposed people for Phase III.  This would also speed things up by many months.

Also, shouldn't the "warp speed" people in the federal government be clamoring to make 300 million doses of this?  The only thing we have to lose is money.  If a better candidate comes along, then at least we'll have the infrastructure in place.

I believe the manufacturing infrastructure will be significantly different depending on the vaccine chosen. Moderna's vaccine is an mRNA vaccine, which would be the first of it's type for human use. I am not close to an expert in this but I suspect making it would be pretty different than making the flu vaccine for instance with eggs. It may in fact be a lot easier to produce an mRNA vaccine at scale, but it will definitely be different.

Some logistics could still be worked out ahead of time either way though. Coming up with all the glass vials you'd need is one thing for instance.

This and the CD4 studies have me feeling positive. I started my 401k contributions again at a low level. Having some Moderna stock would be even better.

It is somewhat concerning to me Moncef Slaoui who was chosen to lead the administration "Warp Speed" project was a former Moderna board member with millions of stock still in the company. Considering how little oversight this administration tolerates, I'm not sure how much I trust that we will have the safest and most efficacious candidate. Hopefully the research results will be transparent and independently evaluable.

[dabigv13]

This is good news. 

I would really like to see challenge trials. If the numbers of cases continue to drop in the US, they're going to be hard-pressed to get a good sample of exposed people for Phase III.  This would also speed things up by many months.

Also, shouldn't the "warp speed" people in the federal government be clamoring to make 300 million doses of this?  The only thing we have to lose is money.  If a better candidate comes along, then at least we'll have the infrastructure in place.

I believe the manufacturing infrastructure will be significantly different depending on the vaccine chosen. Moderna's vaccine is an mRNA vaccine, which would be the first of it's type for human use. I am not close to an expert in this but I suspect making it would be pretty different than making the flu vaccine for instance with eggs. It may in fact be a lot easier to produce an mRNA vaccine at scale, but it will definitely be different.

Some logistics could still be worked out ahead of time either way though. Coming up with all the glass vials you'd need is one thing for instance.

This and the CD4 studies have me feeling positive. I started my 401k contributions again at a low level. Having some Moderna stock would be even better.

It is somewhat concerning to me Moncef Slaoui who was chosen to lead the administration "Warp Speed" project was a former Moderna board member with millions of stock still in the company. Considering how little oversight this administration tolerates, I'm not sure how much I trust that we will have the safest and most efficacious candidate. Hopefully the research results will be transparent and independently evaluable.

[BostonCard]

I think the safety risks are understated.  They saw multiple grade 3 systemic reactions in a sample size of 15 at the highest dose, and one grade 3 reaction at the middle dose.  It will be less common at lower doses, but I would expect to see some cases as the numbers are increased, probably even at the 50 µg dose they are moving to phase 2.  It is a bit concerning that they didn't advance the 25 µg dose forward.

BC

[BostonCard]

I think the safety risks are understated.  They saw multiple grade 3 systemic reactions in a sample size of 15 at the highest dose, and one grade 3 reaction at the middle dose.  It will be less common at lower doses, but I would expect to see some cases as the numbers are increased, probably even at the 50 µg dose they are moving to phase 2.  It is a bit concerning that they didn't advance the 25 µg dose forward.

BC

[burger]

I think the safety risks are understated.  They saw multiple grade 3 systemic reactions in a sample size of 15 at the highest dose, and one grade 3 reaction at the middle dose.  It will be less common at lower doses, but I would expect to see some cases as the numbers are increased, probably even at the 50 µg dose they are moving to phase 2.  It is a bit concerning that they didn't advance the 25 µg dose forward.

BC

What's the typical rate of fevers, etc. for an approved vaccine?  I recall getting a fever once from a vaccination (flu shot maybe? it was a long time ago).

More generally, does anyone know what the success rate for vaccines that make phase 2 or 3 is?  I realize that all diseases and vaccines are different--I'm just curious what our expectations should be all else being equal.  I tried to look this up but couldn't find anything general.

[burger]

I think the safety risks are understated.  They saw multiple grade 3 systemic reactions in a sample size of 15 at the highest dose, and one grade 3 reaction at the middle dose.  It will be less common at lower doses, but I would expect to see some cases as the numbers are increased, probably even at the 50 µg dose they are moving to phase 2.  It is a bit concerning that they didn't advance the 25 µg dose forward.

BC

What's the typical rate of fevers, etc. for an approved vaccine?  I recall getting a fever once from a vaccination (flu shot maybe? it was a long time ago).

More generally, does anyone know what the success rate for vaccines that make phase 2 or 3 is?  I realize that all diseases and vaccines are different--I'm just curious what our expectations should be all else being equal.  I tried to look this up but couldn't find anything general.

[dabigv13]

Maybe 5 to 10 percent of patients can have a fever after a flu shot. Considering the worst reaction they had in the medium dose was just skin redness, that seems alright. Definitely true that this sample was small.

BC, I think they may study the low dose in their phase 3 study, but not phase 2. They don't seem to indicate why in the press release.

"Moderna anticipates the dose for the Phase 3 study to be between 25 µg and 100 µg and expects Phase 3 trial initiation in July, subject to finalization of the clinical trial protocol."

[dabigv13]

Maybe 5 to 10 percent of patients can have a fever after a flu shot. Considering the worst reaction they had in the medium dose was just skin redness, that seems alright. Definitely true that this sample was small.

BC, I think they may study the low dose in their phase 3 study, but not phase 2. They don't seem to indicate why in the press release.

"Moderna anticipates the dose for the Phase 3 study to be between 25 µg and 100 µg and expects Phase 3 trial initiation in July, subject to finalization of the clinical trial protocol."

[BostonCard]

I just looked up the AE grading system used for vaccines, which is available from the FDA here:

https://www.fda.gov/media/73679/download

An AE of grade 3 erythema is > 10 cm, which would probably be acceptable if that were the only thing they saw.

Grade 3 systemic symptoms is a bit vague, but here are the definitions from the FDA of various vital signs:
Fever of 102.1 to 104
Tacycardia to > 130
Hypotension to < 80 mmHg
Respiratory rate to > 25

Most symptoms would need to impair daily activities to qualify as grade 3. It would require narcotics for treatment of a headache, or IV hydration for nausea and vomiting.

In other words, a grade 3 AE for a vaccine is no joke.

BC

[BostonCard]

I just looked up the AE grading system used for vaccines, which is available from the FDA here:

https://www.fda.gov/media/73679/download

An AE of grade 3 erythema is > 10 cm, which would probably be acceptable if that were the only thing they saw.

Grade 3 systemic symptoms is a bit vague, but here are the definitions from the FDA of various vital signs:
Fever of 102.1 to 104
Tacycardia to > 130
Hypotension to < 80 mmHg
Respiratory rate to > 25

Most symptoms would need to impair daily activities to qualify as grade 3. It would require narcotics for treatment of a headache, or IV hydration for nausea and vomiting.

In other words, a grade 3 AE for a vaccine is no joke.

BC

[GoodGrief]

Good thing I bought stock in Moderna 6 weeks ago. Bad thing is I only bought $3000.

As I recall, you also liquidated your stock holdings a short time before the pandemic hit. You should stay a doctor because the world needs it, but boy you seem like you’d make a great fund manager.

[GoodGrief]

Good thing I bought stock in Moderna 6 weeks ago. Bad thing is I only bought $3000.

As I recall, you also liquidated your stock holdings a short time before the pandemic hit. You should stay a doctor because the world needs it, but boy you seem like you’d make a great fund manager.

[BostonCard]

Only if he bought back into the market in early April.  The NASDAQ is positive for the year.  The DOW and S&P 500 are roughly where they were all the way back in August of 2019 (unless, of course, the market tanks again, which is definitely possible).

BC

[BostonCard]

Only if he bought back into the market in early April.  The NASDAQ is positive for the year.  The DOW and S&P 500 are roughly where they were all the way back in August of 2019 (unless, of course, the market tanks again, which is definitely possible).

BC

[fullmetal]

I don't know if it's Moderna or what, but the market as a whole seems to be quite happy today.

[fullmetal]

I don't know if it's Moderna or what, but the market as a whole seems to be quite happy today.

[chrisk]

I don't know if it's Moderna or what, but the market as a whole seems to be quite happy today.

Moderna and Powell

[chrisk]

I don't know if it's Moderna or what, but the market as a whole seems to be quite happy today.

Moderna and Powell

[akiddoc]

Only if he bought back into the market in early April.  The NASDAQ is positive for the year.  The DOW and S&P 500 are roughly where they were all the way back in August of 2019 (unless, of course, the market tanks again, which is definitely possible).

BC

I liquidated most stocks at the market high.
I didn't sell Amazon though, and I have a lot of it. It has done quite nicely since then.

[akiddoc]

Only if he bought back into the market in early April.  The NASDAQ is positive for the year.  The DOW and S&P 500 are roughly where they were all the way back in August of 2019 (unless, of course, the market tanks again, which is definitely possible).

BC

I liquidated most stocks at the market high.
I didn't sell Amazon though, and I have a lot of it. It has done quite nicely since then.

[BostonCard]

Hold your horses on that Moderna vaccine:

https://www.statnews.com/2020/05/19/vacc...9-vaccine/

Not so much any red flags, but more along the lines of the data that Moderna provided is not enough to conclude one way or another.

“My guess is that their numbers are marginal or they would say more,” Rose said about the company’s SARS-2 vaccine, echoing a suspicion that others have about some of the company’s other work.

BC

[BostonCard]

Hold your horses on that Moderna vaccine:

https://www.statnews.com/2020/05/19/vacc...9-vaccine/

Not so much any red flags, but more along the lines of the data that Moderna provided is not enough to conclude one way or another.

“My guess is that their numbers are marginal or they would say more,” Rose said about the company’s SARS-2 vaccine, echoing a suspicion that others have about some of the company’s other work.

BC

[Hurlburt88]

a long way to go . . . shots on goal!

[Hurlburt88]

a long way to go . . . shots on goal!

[newguy]

the Oxford University/AstraZeneca vaccine trials appear to be progressing as well, according to the BBC:

https://www.bbc.com/news/business-52751661

[newguy]

the Oxford University/AstraZeneca vaccine trials appear to be progressing as well, according to the BBC:

https://www.bbc.com/news/business-52751661

[82lsju]

Moderna, which partnered with vaccine manufacturer Lonza Group (LONN.Switzerland) in early May, expects to be able to manufacture one billion doses a year, Tenthoff said. At two doses per patient, “they could cover the entire United States by next year,” Tenthoff said. “But there is obviously global demand beyond what just Moderna is doing'

 
https://www.barrons.com/articles/a-coron...1590072412

[82lsju]

Moderna, which partnered with vaccine manufacturer Lonza Group (LONN.Switzerland) in early May, expects to be able to manufacture one billion doses a year, Tenthoff said. At two doses per patient, “they could cover the entire United States by next year,” Tenthoff said. “But there is obviously global demand beyond what just Moderna is doing'

 
https://www.barrons.com/articles/a-coron...1590072412

[BostonCard]

Uh... yikes, this is not a good look:

https://www.cnn.com/2020/05/22/investing...index.html

It is noted that the stock sales had been planned in advance under the 10b5-1 rules.  However, what is a little sketchy is that Moderna had complete control over when it issued the press release, and as some people have noted, the press release was issued before all data was back.  So, a conspiracy minded person might wonder if the CMO and CFO knew they had impending sales and worked to release the results of the study earlier to ensure that the stock went up before their scheduled sales were due to be executed.

BC

[BostonCard]

Uh... yikes, this is not a good look:

https://www.cnn.com/2020/05/22/investing...index.html

It is noted that the stock sales had been planned in advance under the 10b5-1 rules.  However, what is a little sketchy is that Moderna had complete control over when it issued the press release, and as some people have noted, the press release was issued before all data was back.  So, a conspiracy minded person might wonder if the CMO and CFO knew they had impending sales and worked to release the results of the study earlier to ensure that the stock went up before their scheduled sales were due to be executed.

BC

[Mick]

Uh... yikes, this is not a good look:

https://www.cnn.com/2020/05/22/investing...index.html

It is noted that the stock sales had been planned in advance under the 10b5-1 rules.  However, what is a little sketchy is that Moderna had complete control over when it issued the press release, and as some people have noted, the press release was issued before all data was back.  So, a conspiracy minded person might wonder if the CMO and CFO knew they had impending sales and worked to release the results of the study earlier to ensure that the stock went up before their scheduled sales were due to be executed.

BC

Just to be clear, that's Chief Medical Officer, not some dumb Chief Marketing Officer.

ChMktgOfr Mick...

[Mick]

Uh... yikes, this is not a good look:

https://www.cnn.com/2020/05/22/investing...index.html

It is noted that the stock sales had been planned in advance under the 10b5-1 rules.  However, what is a little sketchy is that Moderna had complete control over when it issued the press release, and as some people have noted, the press release was issued before all data was back.  So, a conspiracy minded person might wonder if the CMO and CFO knew they had impending sales and worked to release the results of the study earlier to ensure that the stock went up before their scheduled sales were due to be executed.

BC

Just to be clear, that's Chief Medical Officer, not some dumb Chief Marketing Officer.

ChMktgOfr Mick...

[BostonCard]

Yes, the Chief Medical Officer would have known of the early results and could have influenced the decision to release them (it probably would have been his call, though the communications group would have handled the details).

BC

[BostonCard]

Yes, the Chief Medical Officer would have known of the early results and could have influenced the decision to release them (it probably would have been his call, though the communications group would have handled the details).

BC