1/2-Doses of Moderna Vaccine? Wait, what?

1/4/22

I wrote earlier today, reporting on the technical head of Operation Warp Speed, Dr. Moncef Slaoui, saying he or they are in talks with Moderna about giving people between the ages of 18 and 55 a half-dose of the COVID-19 vaccine. This was seemingly in response to the government’s pretty crappy roll-out of the vaccine distribution. I wrote, in part:

“What seems most puzzling about this approach isn’t whether it would be effective, but that actual vaccine production does not appear to be the reason why vaccinations are lagging. Slaoui indicated that 17.5 million does in the U.S. had been shipped as of yesterday, with 1.5 million people receiving the shots in the preceding 72 hours, which is about 500,000 per day. Although this appears to be an improvement over the first couple weeks, the bottleneck appears to be somewhere after the manufacturing process, not from the manufacturing process.”

I want to go back to this. I’m a medical writer and I have a degree in microbiology, but otherwise, I’m not an expert on vaccines or immunology. Still, my personal reaction to this is: WTF?

Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID), seemingly in response to Slaoui’s comment on a Sunday morning talk show, at a different talk show, said, “We know what the science tells us. So my feeling … is let’s do it the way the clinical trials have instructed us to do it. But let’s get more efficient into getting it into people’s arms.”

Not to put words in Tony Fauci’s mouth, but I think “WTF?” might have been in the back of his mind.

If there’s evidence that the Moderna vaccine was going to be as effective with a half a dose, it really hasn’t been reported anywhere by Moderna. Same goes for Pfizer and BioNTech. And if it was, why not do it that way to begin with?

Of course, AstraZeneca and the University of Oxford, on the other hand, did report something along those lines, although one might reasonably say WTF? to that report. To reiterate for anyone who hasn’t been following this: in about 1800 patients in a clinical trial, they received a half-dose of the first shot of the Astra-Oxford vaccine by accident. Oops! But weirdly, that cohort had an efficacy rate of about 90% compared to about 62% in the full-dose-first-shot cohorts.

I haven’t heard of many vaccine experts or immunologists who are particularly excited about that data. Confused, yeah. Concerned, sure. And I heard of at least one biostatistician who wondered if it wasn’t just a statistical blip.

It makes one wonder if Warp Speed is trying to extrapolate from one clinical trial to another. It also makes one–okay, me!–wonder if Slaoui and/or Operation Warp Speed and/or Trump, are trying to divert attention away from the clusterf#$# that the initial rollout of this vaccine has been. After all, about the only person taking the blame is General Gustave Perna, who’s heading Warp Speed’s logistics operation. Give him credit for that.

And on a personal level, I’m not terribly surprised by the slow rollout. What they’re trying to do is completely unprecedented. And how it’s going so far rather closely resembles the Trump admin’s PPP efforts last March and April, and their COVID-19 testing efforts since, well, forever. I actually have quite a bit of faith in Slaoui and Perna, although more in Fauci, while I have little or none in the Trump admin. About the only thing they’ve done right is throw money at vaccine development. They probably should have thrown more money at the distribution problem at the state levels and done so earlier.

Personally, I’ll think it’ll scale up as states get on terms with Warp Speed and some very smart people at state and regional health systems finally stand up and say, “Y’know, let us handle it, we know what we’re doing.”

Meanwhile, my Spidey-Sense is tingling at Slaoui’s comment. I’d prefer the full dose, thanks.

COVID-19 Vaccines: 1st US Patient Dosed & Continuing Trials

By Mark Terry

December 14, 2020

1st Patient Receives Pfizer-BioNTech COVID-19 Vaccine in the U.S.

Sandra Lindsay, a nurse at Long Island Jewish Medical Center is the first U.S. patient to receive the COVID-19 vaccine created by Germany’s BioNTech and U.S.-based Pfizer. Lindsay is a critical care nurse at the hospital in Queens, New York City.

She told CNN, “I feel hopeful today, relieved. I feel like healing is coming. This marks the beginning of the end of a very painful time in our country.”

Moderna

Moderna’s vaccine is up next, with the FDA’s vaccine adcom meeting on Thursday, December 17. If it moves like the Pfizer-BioNTech vaccine last week—and there’s no particular reason to believe it will be otherwise at this point—the vaccine will receive Emergency Use Authorization (EUA) sometime on Friday, December 18 or possibly Saturday the 19th, and distribution will begin over the weekend and someone somewhere in the U.S. will receive the first of the Moderna shots sometime on Monday, December 21.

So Then What?

The Pfizer-BioNTech and Moderna vaccines, both mRNA vaccines, require two doses about 28 days apart. It seems to take a couple weeks to build up some immunity—typical of most vaccines—and although the second shot is needed to grant the full potential of the vaccine, both of which in clinical trials demonstrated about 95% efficacy, the clinical trials have suggested that some immunity begins in a week or so of the first injection. So people receiving the shot should still continue wearing masks, practice social distancing, and wash their hands thoroughly and regulatory.

CureVac Launches Phase IIb/III Trial of its Own COVID-19 Vaccine

Germany’s CureVac announced it has enrolled the first volunteer in the pivotal Phase IIb/III trial of its own mRNA vaccine candidate, CVnCoV against COVID-19. In early-stage trials, the vaccine was generally well-tolerated at all doses and induced strong antibody responses as well as the first indication of T-cell activation. The immune response was similar to that observed in recovered COVID-19 patients. The trial will utilize a 12-microgram dose.

The Phase IIb/III trial, dubbed HERALD, will include more than 35,000 volunteers in Europe and Latin America. The HERALD trial will begin with the Phase IIb section, which is expected to merge directly into the Phase III efficacy portion. Participants 18 years or older will receive a two-dose regiment of either the vaccine or a placebo.

Leading Vaccines

Although so much attention has been paid to Pfizer-BioNTech, Moderna and the AstraZeneca-University of Oxford COVID-19 vaccines, they are not the only ones in late-stage trials. Although it’s hard to say what will happen to some of the later-developing vaccines as the frontrunners are rolled out and the pandemic begins to ebb, but many that will have vaccines available in 2021 will presumably help with limited manufacturing of the Pfizer-BioNTech, Moderna and AstraZeneca-Oxford vaccines. Here’s a few others:

CanSino—In limited use in China.

Gamaleya—Russia’s Sputnik V vaccine, which has also begun early use in Russia. AstraZeneca is also going to test their own vaccine in combination with Sputnik V.

Johnson & Johnson—Currently in Phase III trials, with interim data expected sometime in March.

NovaVax—Phase III

Vector Institute—In limited use in Russia, but is otherwise in Phase I and II trials.

Sinopharm-Beijing—Approved in the United Arab Emirate (UAE), Bahrain, and limited use in China.

Sinopharm-Wuhan‑Limited use in China and the UAE.

Sinovac—Limited use in China.

AnGes—This Japanese company is currently running Phase II/III trials with Osaka University and Takara Bio.

Medicago & GlaxoSmithKline—Canada-based Medicago, partially funded by cigarette maker Philip Morris, grows vaccines in a wild species of tobacco, Nicotiana benthamiana. It is currently in a Phase II/III clinical trial.

Anhuei Zhifei Longcom and the Chinese Academy of Medical Sciences—Currently in Phase III.

Bharat Biotech—In collaboration with the Indian Council of Medical Research and the National Institute of Virology, the Indian company’s Cvaxin is in Phase III trials.

Weekend Update

By Mark Terry

December 13, 2020

Sometimes the biopharma industry takes a break on the weekend, but apparently not during the pandemic. Here’s a peek at 3 stories from the weekend.

Pfizer-BioNTech COVID-19 Vaccine Rolls Out—Literally

After the FDA granted the Pfizer-BioNTech COVID-19 vaccine Emergency Use Authorization (EUA) on Friday night, December 11, the vaccine roll-out began—literally—on Sunday. Semi-trucks left the loading dock at Pfizer’s manufacturing facility in Kalamazoo, Michigan, on Sunday to deliver the vaccine in its specialized cold-temp storage containers, to head to airports and distribution centers.

TCR2 Therapeutics’ T-cell Receptor Fusion Construct Promising in Solid Tumors, Including Ovarian

TCR2 Therapeutics, which is yet another Cambridge, Mass. biotech company, announced positive interim data from their ongoing Phase I portion of TC-210 (gavacabtogene autoleucel—“gavo-cel”) Phase I/II trial for mesothelin-expressing solid tumors. As of the Nov. 24, 2020 data cutoff, 3 partial responses (PR) were recorded according to RECIST 1.1 criteria in the first 8 patients; and the first ovarian cancer patient achieved a confirmed PR up to month 6.

Gavo-cel is what they’re calling a T-cell receptor fusion construct. What this means in slightly more clear English, is that the company is fusing tumor antigen recognition domains to T-cell receptors. This basically creates immune cells more finely tuned to attack specific cancers. They’re also believed to be safer than, say, CAR-T therapies, because they shouldn’t create cytokine release syndrome.

AstraZeneca’s Dropping $39 Billion to Buy Alexion

The UK’s AstraZeneca is buying Boston’s Alexion Pharmaceuticals for a tasty $39 billion, which comes to $175 per share. Alexion shareholders will be able to bank $60 in cash per share and 2.1243 AstraZeneca American Depositary Shares (ADSs), which are equivalent on half of one ordinary AstraZeneca share, for each Alexion share.

Pascal Soriot, the AstraZeneca chief exe, stated, “Alexion has established itself as a leader in complement biology, bringing life-changing benefits to patients with rare diseases. This acquisition allows us to enhance our presence in immunology.”

It also pretty much doubles down on rare diseases, a profitable corner of biopharma. AstraZeneca’s focus these days is in oncology, cardiovascular, renal and metabolism, and respiratory diseases. They’ve been getting a rather lot of coverage for their COVID-19 vaccine that they’ve partnered with the University of Oxford on, and which might be submitted to the FDA and other regulators for emergency use authorization before the end of the year or shortly afterwards.

AbbVie Moves Ahead on Plaque Psoriasis Application and Arthritis Clinical Trial

 

By Mark Terry

AbbVie has submitted a Biologics License Application (BLA) to the U.S. FDAfor risankizumab, an interleukin-23 (IL-23) inhibitor for plaque psoriasis.

The application is based on data from four Phase III clinical trials: ultIMMA-1, 2, IMMhance and IMMvent. The drug met all co-primary and ranked secondary endpoints with no new safety problems.

The drug was developed in a collaboration with Boehringer Ingelheim.

In the trials, more than 2,000 patients were treated.

“The risankizumab submission represents an important milestone in our goal of advancing treatment for people living with immune-mediated diseases,” said Michael Severino, AbbVie’s executive vice president, research and development and chief scientific officer. “Risankizumab has the potential to be an important treatment option for people living with plaque psoriasis and we look forward to working with the FDA throughout the review process.”

AbbVie also announced positive data from its ongoing Phase IIB/III SELECT-SUNRISE clinical trial. This trial evaluated upadacitinib in Japanese patients for moderate to severe rheumatoid arthritis. The data showed that at 12 weeks, all doses, 7.5mg, 15mg, 30mg, once-daily, met the primary endpoint of ACR20alpha compared to placebo.

“We are encouraged by these data, which show that upadacitinib provides improvements in important measures such as achieving ACR response and clinical remission, in people living with rheumatoid arthritis in Japan,” Severino said in a statement. “SELECT-SUNRISE reflects our continued commitment to offering innovative solutions with the potential to improve the lives of Japanese patients living with this serious, debilitating condition.”

Upadacitinib was discovered and developed by AbbVie. It is an oral drug that inhibits JAK1, which is linked to various immune-mediated diseases, including rheumatoid arthritis, psoriatic arthritis, and Crohn’s disease. In addition to those diseases, the drug is being evaluated for ulcerative colitis, ankylosing spondylitis, atopic dermatitis and giant cell arteritis.

AbbVie will be releasing its first-quarter financials tomorrow. In the last quarter, it reported a 2.78% increase in earnings, which was more than most analysts expected. Generally, the stock has outperformed the industry this year, which may not be saying much. The industry has shown an overall drop of 4.3% and AbbVie’s have decreased 4.1%.

Shares are currently trading for $91.3. The 52-week high was $125.86 and the low was $64.61. Shares opened today at $90.96.

Also today:

PixarBio CEO and 2 Associates Arrested and Charged with Fraud

Stock Dives as Celldex Cuts 20% of Staff After Phase II Breast Cancer Failure

Corvidia Raises $60 Million Series B to Push into the Clinic

Novartis Joins Innovative Solution Trend for Clinical Trials: Launches FocalView App

Amgen’s New Products Deliver Double-Digit Growth While Facing Down Pricing Pressure for New Migraine Drug

AstraZeneca’s Imfinzi Double-Combo Fails to Impress

By Mark Terry

AstraZeneca and MedImmune announced that their Phase III ARCTIC clinical trial in locally-advanced or metastatic non-small cell lung cancer (NSCLC) in patients who received a least two prior treatments failed to hit its primary endpoint.

The trial was looking at a combination of Imfinzi (durvalumab) and tremelimumab, as well as Imfinzi and tremelimumb by themselves, compared to standard-of-care chemotherapy in patients with PDL1-low/negative. It also looked at Imfinzi alone versus standard chemo in patients with high PDL-1.

Sub-study B, which was in PDL-1-low/negative lung cancer, the combination of Imfinzi and tremelimumab did not meet the primary endpoints, which were progression-free survival (PFS) and overall survival (OS) compared to standard of care.

The company stated that “sub-study A was not powered for statistical significance,” but goes on to say Imfinzi by itself had a clinically-meaningful decrease in the risk of death compared to standard chemotherapy.

“While we are disappointed that the combination of Imfinzi plus tremelimumab did not result in a statistically-significant benefit in this heavily pre-treated patient population, we are encouraged by the activity of Imfinzi monotherapy observed in this trial and look forward to presenting the full data form the ARCTIC trial at an upcoming medical meeting,” stated Sean Bohen, AstraZeneca’s executive vice president, Global Medicines Development and chief medical officer.

The ARCTIC trial was a randomized, open-label, multi-center, global Phase III trial. Tumor PD-L1 expression was evaluated using the Ventana PD-L1 (SP263) assay with PD-L1 high defined as 25% or more tumor cells with membrane staining.

Imfinzi is a human monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80. It basically keeps tumors from hiding from the body’s immune system. Tremelimumab is also a fully human monoclonal antibody, in this case, against CTLA4. It is an immune checkpoint blocker.

The U.S. FDAapproved Imfinzi for patients with unresectable, Stage III NSCLC whose disease hadn’t progressed after platinum-based chemo and radiation therapy. It’s also been granted accelerated approval in the U.S. for locally-advanced or metastatic urothelial carcinoma after disease progression after platinum-based chemo, or in patients whose disease progressed within a year of receiving platinum-containing chemo before or after surgery.

Following in the footsteps of HIV treatment, immuno-oncology has been working on the value of combination therapies, but the results of this study undercut the possibilities—although not by too much. Reutersnoted, “The results of the study, known as ARCTIC, is disappointing but not a huge surprise, since evidence has been building that there may be little value in using a so-called CTLA-4 drug like tremelimumab on top of a PD-L1 such as Imfinzi.”

Like most therapies, monotherapy or combinations, it depends on the diseases and the drugs. Because Imfinzi showed some efficacy, but adding tremelimumab didn’t, there’s a possibility that adding tremelimumb offset Imfinzi’s efficacy. Immuno-oncology therapies with traditional chemo appear to be effective, but adding multiple immuno-therapies together, at least as demonstrated by this study, do not seem terribly effective.

Reuters went on to write, “A year ago, the notion of combining the two medicines was the big hope driving AstraZeneca’s stock price—but that hope was dealt a major blow in July when its main first-line lung cancer trial, called MYSTIC, failed to slow disease progression.”

AstraZeneca is planning to report overall survival data from the MYSTIC trialin the second half of this year. MYSTIC is evaluating Imfinzi alone or in combination with tremelimumb compared to standard chemo in patients with epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) wild-type locally-advanced or metastatic (Stage IV) first-line NSCLC.

As of this writing, AstraZeneca stock is up about 1.3% in trading, hitting $35.08. It dropped slightly at opening, but is recovering.

Also today:

Takeda Pharma and Shire Come Back to the Negotiating Table

New Sanofi R&D Boss Marks Yet Another High-Profile Industry Executive Change

Revolution Medicines Raises Another $56 Million and Completes Pivot from Antifungal to Cancer Company

Eli Lilly’s Arthritis Drug Gets Mixed Recommendation, But Reports Strong Quarter

Cedilla Therapeutics Launches with $56.2 Million

BioPharmBiz

Welcome to BioPharmBiz. This site will present news and insight related to the biopharmaceutical industry—biotech, pharmaceuticals and medical devices. The site is under construction at the moment, so please be patient.

 

Cheers,

Mark Terry