Cassava: Alzheimer’s Study Results Are Promising but It’s Early Days, Says Analyst

 The effect clinical trial results can have on a pharma company’s stock are tremendous and can work both ways. Disappoint investors and a sharp descent for the shares is likely. Conversely, release encouraging news, and the sky’s the limit.

It is safe to say that in the case of Cassava Sciences (SAVA), investors were very happy following its latest news release.

Cassava shares are up nearly 210% (at one point, the stock was up over 490%) this week, after the company disclosed encouraging interim data from an open-label study of its Alzheimer’s disease candidate simufilam.

The study, which was funded by the National Institutes of Health (NIH), found that six months after treatment began, 50 Alzheimer's disease patients exhibited a 10% improvement in their cognitive functions. Furthermore, dementia-related behavior, such as delusions, anxiety, and agitation, also improved by 29%.

The company is now in talks with the FDA about a Phase 3 trial, which is anticipated to kick off in 2H 2021.

Alzheimer's is a progressive disease, which over time causes sufferers’ cognitive abilities to decline. Therefore, the results are even more eye-catching.

In the U.S. alone, almost 6 million people suffer from the memory-obliterating disease, and there are presently no available drugs that can stem its progress. Accordingly, a successful treatment could be very lucrative.

So, it is no wonder the market’s reaction to the data was so upbeat. However, Cantor analyst Charles Duncan takes a more measured view.

“Although we find these data provocative and encouraging, we interpret the observations with caution, as it is an open-label study that can be confounded by variables, such as expectation bias,” the 5-star analyst said. "With long-term dosing there may be notable dose-dependent differences or, perhaps, a safety signal that may advantage titration with the higher dose."

However, Duncan summed up, "these results do not alter our fundamental views and thesis, nor do they change the risk we associate with this program."

Duncan’s “fundamental view” says Cassava is an Overweight (i.e. Buy), and the rating is backed by a $24 price target. That said, the stock’s massive surge means the share price is now ~57% above Duncan’s figure. (To watch Duncan’s track record, click here)

Other analysts are in the same boat. While the 2 additional reviews are both Buys, the Strong Buy consensus rating comes with a $19.33 average price target attached. From current levels, it is a sharp ~69% drop. It will be interesting to see whether the analysts upgrade their price targets or downgrade their ratings over the coming months. (See SAVA stock analysis on TipRanks)

https://finance.yahoo.com/news/cassava-alzheimer-study-results-promising-153618638.html

Ocugen: New Potential Covid-19 Vaccine at the Gate

 It’s official, a new Covid-19 vaccine candidate has entered the fray.

On Tuesday, Ocugen (OCGN) announced it had finalized its deal with India-based Bharat Biotech. The two will work together on COVAXIN, Bharat’s Covid-19 vaccine, for the U.S. market.

Ocugen will take on all aspects of U.S. based responsibilities, including clinical development, regulatory approval, and commercialization. If the vaccine is granted an EUA, Bharat anticipates supplying the U.S. market’s initial COVAXIN doses.

Bharat, in return, will be eligible for 55% of U.S. sales’ profits, with Ocugen retaining the other 45%.

Ocugen gets a head start, as COVAXIN has already been granted emergency use authorization in India. It is also currently in a Phase 3 study with 25,800 subjects enrolled.

H.C. Wainwright analyst Swayampakula Ramakanth says the vaccine has qualities which set it apart from the competition.

“Compared to COVID-19 vaccines currently authorized under EUA, COVAXIN could induce more broad immunity targeting multiple viral proteins, potentially resulting in better protection against emerging mutant viruses, such as the UK and South African variants,” the 5-star analyst noted. “Additionally, COVAXIN only requires a standard vaccine storage temperature, compared to the more stringent storage requirements for the mRNA vaccines.”

The vaccine, therefore, “could strengthen the arsenal to fight against the pandemic.”

Ocugen is already in talks with the FDA and the Biomedical Advanced Research and Development Authority (BARDA) to map out the path forward to “a successful EUA.”

Given the dire need for Covid-19 vaccines, Ramakanth believes that should the Indian Phase 3 study display more than a 50% success rate, there’s a possibility the FDA could make an “unprecedented move” and grant COVAXIN EUA status.

“Therefore,” the analyst summed up, “We believe COVAXIN has the potential to deliver significant upside in the next 6-12 months.”

As a result, Ramakanth upgraded Ocugen’s rating from Neutral (i.e. Hold) to Buy with a $4.5 price target. The implication for investors? Upside of 60% for the coming year. (To watch Ramakanth’s track record, click here)

Ramakanth’s colleagues back up his call, as all 3 other recent Ocugen reviews say Buy. OCGH's Strong Buy consensus rating is backed by a $4.30 average price target, suggesting a ~30% premium will be added to the shares in the year ahead. (See OCGN stock analysis on TipRanks)

https://finance.yahoo.com/news/ocugen-potential-covid-19-vaccine-163624031.html

FDA Shrinks Scope of Convalescent Plasma For COVID-19

 The FDA limited the scope of authorized COVID-19 convalescent plasma use to a subset of hospitalized patients, in a revision issued on Thursday.

According to the updated emergency use authorization (EUA), only high-titer convalescent plasma should be used, and only for a narrower population: hospitalized patients early in disease course and those with impaired humoral immunity who cannot produce an adequate endogenous antibody response. Low-titer convalescent plasma is no longer authorized for use.

These recommendations were based on updated data from clinical trials, the FDA said, specifically citing research from the expanded access protocol from the Mayo Clinic, as well as other smaller trials.

Data from the Mayo Clinic trial was published in an August preprint, but not in a peer-reviewed journal until January. The journal publication indicated that higher-titer plasma was associated with a lower risk of death than lower-titer plasma, and patients receiving the treatment who were non-mechanically ventilated had a lower risk of death than those receiving mechanical ventilation.

"Based on assessment of these data, potential clinical benefit of transfusion of COVID-19 convalescent plasma in hospitalized patients with COVID-19 is associated with high titer units administered early in the course of disease," the agency wrote. "Transfusion of COVID-19 convalescent plasma in hospitalized patients late in the course of illness (e.g., following respiratory failure requiring intubation and mechanical ventilation) has not been associated with clinical benefit."

A Fact Sheet for Providers has also been updated to include this information about lack of clinical benefit in intubated patients.

Controversy has always followed use of convalescent plasma for COVID-19, which was authorized in August a day after a tweet from President Trump to former FDA Commissioner Stephen Hahn, MD, nudging him about its authorization. Hahn was later forced to walk back certain claims he made about the treatment at a press conference, which had exaggerated the clinical benefit.

The EUA for convalescent plasma was revised at least once before. In November, the agency added a requirement for an additional test in convalescent plasma manufacture to qualify high-titer plasma. Nine tests are now authorized for this purpose, the FDA said.

https://www.medpagetoday.com/infectiousdisease/covid19/91071

Did Convalescent Plasma for COVID-19 Unleash Viral Mutation?

 An immunosuppressed patient with COVID-19 in England developed viral mutations last summer -- including one included in the notorious B.1.1.7 or "U.K. variant" -- after treatment with convalescent plasma, researchers found.

A man in his 70s, who had received immunotoxic chemotherapy in 2012 to treat lymphoma, was hospitalized with COVID-19 and treated with antibiotics, steroids, and remdesivir. However, following treatment with convalescent plasma in July, genomic sequencing revealed the patient acquired viral mutations, including a deletion present in the B.1.1.7 variant, reported Ravindra Gupta, MD, PhD, of University of Cambridge in England, and colleagues.

"We have documented a repeated evolutionary response by SARS-CoV-2 in the presence of antibody therapy during the course of a persistent infection in an immunocompromised host," the authors wrote in an unedited but peer-reviewed manuscript published in Nature.

The man died in late August. Gupta's group did not claim that he was the first to develop the B.1.1.7 mutation or that it spread from him to other people. Rather, they speculated that the plasma therapy had unleashed the resistant variants, and could do so in other immunosuppressed patients too.

In such patients, they wrote, "the antibodies administered [in plasma] have little support from cytotoxic T cells, thereby reducing chances of clearance and theoretically raising the potential for escape mutations."

Consequently, they cautioned against using convalescent plasma in severe COVID-19 patients and especially in those with compromised immune function.

"The data from this single case report might warrant caution in use of convalescent plasma in patients with immune suppression of both T cell and B cell arms," they wrote, suggesting it should only be used in immunosuppressed patients as part of observational studies with appropriate infection control precautions.

The FDA recently limited the scope of its emergency use authorization of convalescent plasma in COVID-19 patients to less severe patients, but did not suggest extra caution in immunosuppressed patients. In fact, the agency said, "The therapeutic window may be longer" when plasma is given to patients with "impaired humoral immunity."

In the British case, the man was initially hospitalized in May with neutropenic sepsis, and tested positive for SARS-CoV-2 about a week later. He was discharged later that month, but readmitted in late June with cough and breathlessness.

His clinical condition deteriorated and he received dexamethasone and two 10-day courses of remdesivir with 5 days in between. Convalescent plasma was administered on two days around July 20; more remdesivir and convalescent plasma was administered about 4 weeks later. He died shortly afterward.

Gupta -- who also documented the second case of HIV remission with the "London patient" in 2019 -- and colleagues collected viral samples from this patient 23 times. During the first 57 days, they found little change in viral population following treatment with remdesivir, but following the July round of convalescent plasma, there was a shift in viral genotype.

Initially the patient's viral serotype showed a mutation first reported in China (a D614G substitution in the spike protein). However, that changed in late July, when a variant with two alterations in the spike protein, including the deletion seen in the B.1.1.7 variant, became prevalent.

Experimental analyses found "two-fold reduced susceptibility of these viruses to convalescent plasma containing polyclonal antibodies," though the researchers said it was not the reason for the ultimate treatment failure.

Gupta and colleagues said this viral evolution is unlikely to occur in immunocompetent patients, as "viral diversity is likely to be lower due to better immune control."

However, they questioned CDC guidance recommending 20 days for afebrile immunocompromised patients as the upper limit of infection prevention, noting they detected "environmental contamination" in a single occupancy room, so the patient was moved to a negative-pressure isolation room.

Limitations to the study included that it was a single case, and samples were taken from the upper respiratory tract, not the lower tract.

Disclosures

The authors disclosed no conflicts of interest.

Primary Source

Nature

Source Reference: Kemp SA, et al "SARS-CoV-2 evolution during treatment of chronic infection" Nature 2021; DOI: 10.1038/s41586-021-03291-y.

https://www.medpagetoday.com/infectiousdisease/covid19/91088

Novel Sleep Apnea Device OK'd

 A new device that prevents the tongue from rolling backwards during sleep, a common proximate cause of snoring and obstructive sleep apnea, won authorization Friday from the FDA.

The eXciteOSA product from Signifier Medical Technologies delivers electrical stimulation to four locations on and below the tongue. The manufacturer says the electrical current strengthens the tongue muscle so that it remains in its proper position during sleep.

Perhaps most noteworthy is that the device -- unlike virtually every other product intended to prevent snoring and sleep apnea -- is for use only when the patient is awake.

Specifically, the FDA explained, patients use the mouthpiece (the system also includes a separate handheld controller and a smartphone app) in daily 2o-minute sessions during wakefulness for 6-8 weeks, then once weekly afterward.

Safety and efficacy were tested in 115 patients with snoring, the FDA said. Participants used the device for 6 weeks followed by a 2-week washout period, at which point their snoring was reassessed. "Overall, the percent of time spent snoring at levels louder than 40dB was reduced by more than 20% in 87 out of the 115 patients," according to the FDA.

Additionally, 48 of these patients also had mild sleep apnea. In 41, the mean Apnea-Hypopnea Index (AHI) declined 48% from baseline (10.21 to 5.27).

The treatment was not without side effects, however. Among them: excessive salivation, tongue or tooth discomfort, tongue tingling, dental filling sensitivity, metallic taste, gagging, and tight jaw, the FDA said.

Authorization also came with contraindications for the following groups:

• Patients with pacemakers or implanted leads
• Those with metallic implants, appliances, or jewelry in the mouth
• Potentially or definitely pregnant individuals
• Patients with sores in or around the mouth
• Individuals with AHI values of 15 or higher

The FDA recommends that patients undergo a comprehensive dental exam prior to initial use.

Because the agency classified the eXciteOSA device as low to moderate risk, it authorized marketing via the de novo premarket review pathway -- an intermediate process between 510(k) notification and full premarket approval.

https://www.medpagetoday.com/pulmonology/sleepdisorders/91082

White House: working to speed early production of J&J COVID-19 vaccine

 The Biden administration is exploring every option for increasing manufacturing of Johnson & Johnson's COVID-19 vaccine, which is under regulatory review, and said on Friday that currently expected levels of early doses were less than hoped.

The White House has invoked the Defense Production Act to help Pfizer Inc ramp up COVID-19 vaccine production and that "every option" was on the table to produce more Johnson & Johnson vaccine should it be authorized.

It will also use the wartime powers to increase at-home COVID-19 tests, and make more surgical gloves in the United States, officials said at a Friday media briefing.

"As is the case with other vaccines, we have not found that the level of manufacturing allows us to have as much vaccine as we think we need coming out of the gate," said Andy Slavitt, senior adviser to the White House’s COVID-19 response team, referring to the J&J vaccine.

J&J applied on Thursday for U.S. emergency use authorization. It expects to have some vaccine ready for distribution as soon as authorized but has not said how much.

Emergent Biosolutions' Chief Executive Robert Kramer said in an interview on Friday that the company currently is making bulk drug substance for J&J "at large scale." Emergent is only producing bulk vaccine, which is then filled into syringes or vials and packaged for shipment by another contractor.

Kramer said they were on track to make enough product for hundreds of millions of doses a year. It remains unclear what other supply bottlenecks may be. Kramer said his company had already benefited from the Defense Production Act under the Trump Administration, which helped the company get to the point where it's ready to go.

Under the authority of the Defense Production Act, the government will give priority ratings to two components important to Pfizer’s vaccine production - filling pumps and tangential flow filtration units, the officials said.

“We told you that when we heard of a bottleneck on needed equipment, supplies, or technology related to vaccine supply that we would step in and help, and we were doing just that,” said Tim Manning, the supply chain coordinator for the national COVID-19 response.

The government will also invoke its powers under the Defense Production Act to increase at-home COVID-19 tests with six, unnamed manufacturers, aiming to produce 61 million tests by the summer, Manning said.

It will also invoke its powers to increase the nation’s supply of surgical gloves, which are made almost exclusively overseas.

Manning said the government will build factories that make the raw materials for surgical gloves and help build plants in the United States to make the gloves.

Officials have said that once J&J's vaccine is authorized, it would mean that millions more doses would be available to states. The vaccine is one-shot, as opposed to Pfizer's and Moderna Inc's two-dose vaccines, and can be stored in a refrigerator.

Officials have hoped that the ease of giving the J&J vaccine will mean that states will be able to more quickly immunize residents.

https://www.marketscreener.com/quote/stock/MODERNA-INC-47437573/news/Moderna-White-House-says-it-is-working-to-speed-early-production-of-J-J-COVID-19-vaccine-32370226/

Sinovac Biotech: COVID-19 vaccine effective in preventing hospitalization, death

 China's Sinovac Biotech on Friday said late-stage trial data of its COVID-19 vaccine from Brazil and Turkey showed the inoculation prevented hospitalization and death in COVID-19 patients, but had a much lower efficacy overall.

The 12,396-person trial found the CoronaVac vaccine was 100% effective for hospitalized, severe and fatal cases, 83.7% effective at stopping cases that require medical treatment and 50.65% for all cases, according to a statement. 

https://www.marketscreener.com/quote/stock/SINOVAC-BIOTECH-LTD-5714593/news/Sinovac-Biotech-says-COVID-19-vaccine-effective-in-preventing-hospitalization-death-32371342/