Amidst Controversy, CytoDyn Reports Early Leronlimab Data in NASH, Breast Cancer

 Controversial biotech company CytoDyn announced two separate stories about its drug leronlimab today, one for nonalcoholic steatohepatitis (NASH) and the other for metastatic triple-negative breast cancer (mTNBC).

Leronlimab is a viral-entry inhibitor, binding to CCR5, protecting T-cells from viral infection. As such, it is being developed for HIV. Its antiviral effects have resulted in it also being developed for COVID-19. Because CCR5 plays a role in tumor invasion, metastases and control of the tumor microenvironment, the drug is also being investigated for certain types of cancer. Additionally, CCR5 is involved in modulating immune cell tracking to inflammation sites, which explains the COVID-19 investigations as well as the NASH studies.

NASH is a form of fatty liver disease, similar to cirrhosis of the liver, but in people who drink little or no alcohol. In the Phase II NASH study, CytoDyn reported preliminary findings from five patients receiving leronlimab. The data suggests the fatty deposits were decreased by as much as 45% in all five patients compared to the baseline measurement. Fibrosis, or scarring, was reduced by as much as 10% in four of the five patients.

“We are encouraged by the preliminary results from the open label portion of our NASH trial,” stated, Chris Recknor, senior executive vice president of Clinical Operations for CytoDyn.

For the breast cancer study, CytoDyn updated results on patients receiving leronlimab who had CCR5+ mTNBC who had failed at least two lines of previous therapy. The ongoing data analysis is from 28 pooled patients, 16 from the company’s Compassionate Use Study, 10 from a Phase Ib/II trial and two from the Basket Study. 

Three-quarters, or 75%, of the patients who showed a lower level of circulating cells after receiving leronlimab, demonstrated a 3600% increase in 12-month overall survival (OS) compared to a 980% increase in OS reported by CytoDyn on August 25, 2021. The updated data also hints at a 580% increase in 12-month Progression Free Survival (PFS) compared to up to a 660% increase in PFS they reported on August 25.

Nader Pourhassan, CytoDyn’s president and chief executive officer, said, “We believe these updated results are very strong. Our chief operating officer, Dr. Nitya Ray, is leading our team in preparing a Breakthrough Therapy application to be submitted to the FDA this week.”

CytoDyn has had more than its fair share of controversy this year. In May, the U.S. Food and Drug Administration (FDA) published a “Statement on Leronlimab,” a rare public scolding by the agency accusing the company of misrepresenting its clinical trial data for leronlimab’s use in COVID-19. The statement focused on results from two clinical trials, CD10 in 86 mild-to-moderate COVID-19 patients, and CD12, in 394 patients, focused on severe symptoms of respiratory symptoms associated with COVID-19.

In March, the company’s Phase III leronlimab trial missed the primary endpoint of minimizing symptoms and missed all secondary endpoints, including if the drug decreased mortality for COVID-19. But CytoDyn put a positive spin on the data, focusing on a subgroup of 62 patients on mechanical ventilation, arguing the drug resulted in a 24% decrease in all-cause mortality and a six-day reduction in hospitalization. They then issued a press release describing an “age adjustment” analysis alleging leronlimab decreased mortality in older patients.

The FDA stated, “It has become clear that the data currently available do not support the clinical benefit of leronlimab for the treatment of COVID-19. None of these analyses met statistical significance when using established and reliable analytical methods that correct for multiple comparison.”

In addition to the stock plunging 27%, a shareholder filed a class-action lawsuit against CytoDyn, alleging it made false and misleading statements about leronlimab’s effectiveness in treating COVID-19. Another similar lawsuit was filed in April.

On September 20, CytoDyn announced it had resolved its lawsuit against the activist investor group led by Paul Rosenbaum and Bruce Patterson. The investor group had issued more than 30 pages of “corrective and new disclosures, including the corrective disclosures previously made in connection with the Court’s Stipulated Order. The new disclosures demonstrate that the Activist Group was not forthcoming with shareholders about its conflicts of interest, sources of funding and agenda at the outset.”

Rosenbaum/Patterson Group had attempted what CytoDyn called “an illegal proxy contest to take over control of the Company’s Board of Directors.”

More recently, STAT published a story suggesting that CytoDyn had knowingly submitted an application to the FDA that was incomplete. CytoDyn then issued a statement alleging that STAT was calling itself a health care journalism publication but instead behaved as a stock market advisory group.

https://www.biospace.com/article/amidst-controversy-cytodyn-reports-early-nash-and-breast-cancer-data-for-leronlimab/

Testimony: Elizabeth Holmes Mislead Investors with Use of Schering-Plough Logo

 One week after a retired Pfizer scientist testified that Theranos inappropriately used the pharma giant’s company logo in marketing materials sent to Walgreens, suggesting its participation in research, a second researcher from a different company made a similar claim.

The Wall Street Journal reported that in testimony this week in the ongoing fraud trial of Elizabeth Holmes, immunology expert Constance Cullen, who headed up test development at Schering-Plough Corp., revealed that Theranos had also inappropriately attached Schering-Plough Corp’s logo to data issued to potential investors. The use of the logo suggested that Schering Plough, which is part of Merck, had validated the claims of Theranos regarding its blood-testing technology.

During her testimony, Cullen described Holmes in similar terms used by Pfizer’s Shane Weber. The Journal said Cullen described Holmes as “cagey,” while Weber testified that she was “deflective” and provided “evasive non-informative answers” to his questions.

In 2009, when Schering-Plough merged with Merck, Cullen and some colleagues traveled to California to validate three tests using the Theranos technology. The company was interested in partnering with Theranos on the development of proprietary tests. According to the Journal, Cullen and her team conducted due diligence, but that meeting did not go well, according to testimony.

“I was dissatisfied, quite honestly,” Cullen testified, according to the report. “There was insufficient technical detail for us to be able to evaluate the technology.”

Cullen told the court that she expected the Theranos team to provide “clear, direct answers” to her questions about the blood-testing technology. She never received them, which echoes the testimony of Pfizer’s Weber.

Cullen also noted in her testimony that Holmes did not allow other Theranos employees to answer questions, even when they were posed directly to them during the meeting. She said Holmes would interrupt the response and answer for them.

Following that meeting between Cullen’s team and Theranos, Holmes sent Cullen a validation report that showed the performance of the Theranos technology on the proprietary devices held by Schering-Plough. The reports concluded that Theranos’ technology “has been shown to give accurate and precise results,” the Journal reported. However, Cullen said she never confirmed those findings. She anticipated follow-up meetings and conversations, but they never occurred.

In early 2010, Holmes then sent a new report to Walgreens in its ongoing attempt to woo that company. The report included the Schering-Plough logo at the top and a different conclusion to the report sent to Cullen months before. The data sent to Walgreens said the Theranos technology “has been shown to give more accurate and precise results.” Cullen testified that no one at Schering-Plough had approved those findings, the Journal said.

Walgreens and Theranos eventually forged a partnership in 2013 that allowed for Theranos to provide testing at some of its locations throughout the Southwest. In 2016, Walgreens officially severed ties with Theranos after the blood-testing startup invalidated results from thousands of tests it had conducted.

In addition to testimony regarding Theranos’ forging of documents to include the corporate logos of companies that did not back her technology, the jury heard testimony from the representative of a wealthy investor who sank $100 million into Theranos. Lisa Peterson, a representative of the DeVos family, which made its fortune as the co-founders of Amway, testified they were provided misleading revenue projections from Theranos and claimed the company had a partnership with the Department of Defense.

https://www.biospace.com/article/elizabeth-holmes-mislead-investors-with-use-of-schering-plough-logo-testimony-reveals/

Amgen strikes while its rival is down

 As Kras inhibition fast moves away from monotherapy and towards the promise of combinations, Amgen has played up its development plan for Lumakras. The move is a shot across the bow of Mirati, which has promised investors an adagrasib/Keytruda combo update next week, but which is mired in a highly distracting C-suite upheaval.

On a third-quarter call yesterday Amgen said that in the first half of 2022 it would report findings from Lumakras combos with Keytruda and Shp2 inhibition, as well as from its confirmatory phase 3 lung cancer trial. The confirmatory study also has the potential to cause Mirati a major headache.

This is because, despite much hype and a multi-billion dollar market cap, Mirati has still not filed adagrasib, its Kras G12C contender. An accelerated filing for NSCLC is due by the end of 2021, but swift conversion of Lumakras’s own accelerated green light into full approval could scupper Mirati’s chances to get adagrasib approved without controlled phase 3 data.

For now Mirati investors are focused on adagrasib’s potential in colorectal cancer, where data at this year’s Esmo meeting impressed, and where Amgen has deprioritised Lumakras. And first-line NSCLC data for adagrasib in combination with Keytruda, expected along with next Monday’s third-quarter release, are also seen as a way for Mirati to leapfrog its rival.

Still, nothing is known about how much efficacy data Mirati actually plans to provide, or indeed whether it will be possible to parse adagrasib’s contribution from this uncontrolled dataset. Leerink analysts reckon a 50% remission rate with favourable safety and signs of activity in PD-L1-low subjects would suggest a head start for adagrasib against Lumakras in front-line NSCLC.

Among the clinical updates Amgen has promised in the first half of next year are Keytruda/Lumakras combo data in solid tumours, but this phase 1 study does not include first-line patients. Amgen is also planning a first-half update on solid tumours other than NSCLC or colorectal, where so far data on just three subjects have been available.

Mirati and Amgen's duelling development plans
	Adagrasib (Mirati)		Lumakras (Amgen)
	Study	Status	Study	Status
≥2L NSCLC monoRx	Krystal-1	Esmo21 update, filing due Q4 2021	Codebreak-100	Accelerated approval for 2L NSCLC
≥2L colorectal monoRx		Esmo21 update, discussion with FDA expected Q4 2021		Disappointed at Asco21
≥2L colorectal, EGFR combo	Krystal-10*	Esmo21 data (Erbitux combo)	Codebreak-101	Esmo21 data (Vectibix combo)
Keytruda combo	Krystal-7	1L NSCLC update due Q4 2021		Solid tumour data H1 2022
Shp2 combo	Krystal-2	First data (TNO155 combo) H1 2022		First data (RMC-4630 combo) H1 2022
Non-NSCLC/colorectal monoRx	–	–		First data H1 2022
BI 1701963 (Sos1) combo	Krystal-14	First data H1 2022	Unclear	Collaboration Sep 2021
2L NSCLC confirmatory ph3, monoRx vs docetaxel	Krystal-12*	Started Q1 2021	Codebreak-200*	Data H1 2022
1L NSCLC (STK11 co-mutation), monoRx	Unclear	Started Q1 2021	Codebreak-201	Starting Nov 2021
Note: selected studies only; *phase 3 trial. Source: Mirati, Amgen & clinicaltrials.gov.

All is by no means lost for Mirati, but the inescapable impression is that, while Amgen has made hay and grabbed a speedy Lumakras approval, Mirati has sat on its hands and presided over a senior management falling-out.

After months of its share price bleeding away value, Mirati unexpectedly appointed David Meek chief executive in September, replacing the founder, Charles Baum. Then two days ago its chief operating officer, Daniel Faga, and chief medical officer, Joseph Leveque, were shown the door. The shares took another 14% hit.

Mirati is still worth nearly $9bn, but investors are desperate for the group to execute, and one hope is that next Monday’s update will also include further clarity on a regulatory filing strategy.

It should also be stressed that while Amgen might be winning the Kras battle it is early days, and numerous other big players are advancing fast. And Amgen has troubles of its own, too: Lumakras may carry 2026 revenue consensus of $2bn, according to Evaluate Pharma, but Bernstein expects biosimilars to erode $13.5bn of the group’s current revenue in 2025-28.

https://www.evaluate.com/vantage/articles/news/corporate-strategy/amgen-strikes-while-its-rival-down

Novo fattens up again

 Novo Nordisk has long contended that obesity is a disease that can and should be treated by drugs in addition to lifestyle changes. The group’s thinking here is starting to pay off, with the strong launch of its new obesity product, Wegovy.

Novo did not release actual Wegovy sales numbers during its earnings today, but overall third-quarter obesity revenues, which also include the older drug Saxenda, jumped 79%. However, it is unclear just how big Wegovy could become, given question marks over broad obesity reimbursement. And competition is looming in the shape of Lilly’s tirzepatide.

For now, though, investors seemed unconcerned, pushing Novo’s stock to another record high today.

Not meeting demand

The group beat expectations in the third quarter, helped by Wegovy’s US launch, which began in June. Demand is continuing to outstrip supply, but Novo believes that it can resolve this issue in early 2022 by accelerating the manufacturing ramp-up that it already had planned.

The fact that initial interest in Wegovy has been much stronger than Novo had anticipated suggests that the Danish group has dropped the ball – but, as noted by analysts at Third Bridge, this is “not the worst problem to have”.

It is hard to ascertain just how good the launch has been. Novo’s chief financial officer, Karsten Munk Knudsen, told a media call today that the group had combined its obesity sales because of volatility in Wegovy prescriptions, but that it hoped to start breaking out revenues for the new drug next year.

It is possible to come up with a rough estimate, based on analyst expectations. Jefferies had forecast total obesity sales of DKK2.35bn ($366m) in the third quarter, with DKK625m of this coming from Wegovy.

In the event, obesity revenues exceeded this, at DKK2.4bn – suggesting Wegovy sales of around DKK647m.

For full-year 2021, Jefferies forecasts Wegovy revenues of DKK2.1bn, meaning that the drug would still have a long way to go to become one of the biggest launches of all time.

Payer buy-in

To keep momentum going, and reach analysts’ sales target of nearly $9bn by 2028, Novo will need to get payers onside. This might not be an easy task: under current US legislation obesity drugs are not reimbursable under Medicare Part D, which covers prescription medications.  

This is something Novo hopes could be reversed, but the likelihood of this scenario is up for debate. The group’s chief executive, Lars Fruergaard Jørgensen, noted that bariatric surgery was currently covered, and added that lacklustre efficacy with older obesity drugs might have contributed to payers’ reluctance to reimburse the latter – implying that with better drugs this could change.

In the meantime, there are other patients for Novo to go after. Of the 110 million people in the US with obesity, roughly half are covered by the commercial market, on which the Danish group is currently focusing its efforts. Three big pharmacy benefit managers now cover Wegovy, representing 60% of that segment.

There are also other countries to consider. A decision in Europe is expected by the end of the year, and Wegovy is also under review in Japan.

Notably, Novo’s international obesity sales grew 51% in the first nine months of the year, driven entirely by Saxenda. Mr Jørgensen speculated that the role of obesity in Covid-19 complications could be a factor.

Tirzepatide is coming

Growing awareness of obesity as an important health issue could be a reason why, on the surface at least, Novo is unconcerned about the threat of competition.

Lilly’s dual GIP/GLP-1 agonist tirzepatide is now with regulators for type 2 diabetes, where it has already shown impressive weight loss. And the project’s first pivotal obesity trial, Surmount-1, is set to complete next April.

Altimmune’s GLP-1/glucagon dual receptor agonist pemvidutide also recently demonstrated a dramatic effect in its phase 1 obesity trial, but liver enzyme elevations have caused concerns. Still, there are a host of other players also taking a combo approach.

Another possible rival could come in the shape of Pfizer’s small-molecule oral GLP1 agonist danuglipron (PF-06882961), which is due to yield proof-of-concept data this year in diabetes, and next year in obesity.

Mr Jørgensen said he welcomed competition, saying this could help expand the obesity market further. It is true that there are plenty of patients to go around, but obesity is a huge part of Novo’s future plans, and it will need to make the most of its head start over Lilly. Sorting out the supply issues with Wegovy would be a start.

https://www.evaluate.com/vantage/articles/news/corporate-strategy/novo-fattens-again

Private S.Korea firms plan $5.4 billion investment to create vaccine hub

 

South Korea's private sector plans to invest 6.3 trillion won ($5.4 billion) in vaccine production and distribution by 2024, as the country seeks to become a global vaccine powerhouse, Prime Minister Kim Boo-kyum said on Tuesday.

South Korea already has deals to produce three coronavirus vaccines developed by AstraZeneca https://www.reuters.com/article/health-coronavirus-southkorea-skbioscien-idUSL3N2N40W5/Oxford University, Novavax, and Russia https://www.reuters.com/business/healthcare-pharmaceuticals/skoreas-gl-rapha-certified-produce-sputnik-covid-19-vaccines-2021-10-26. It also has a vaccine bottling and packaging agreement with Moderna https://www.reuters.com/article/health-coronavirus-southkorea-moderna-idUSL4N2RM0VP.

The investment plan includes 4.24 trillion won spending by Samsung BioLogics and 1.5 trillion won by drugmaker Celltrion, the government data showed.

Kim said the government had selected 14 companies in the vaccine supply chain eligible for 18 billion won of state financial support, as the government develops the industry to become a major pillar.

The selected companies include Hanmi Pharmaceuticals, ST Pharm and Cellid.

The move comes after President Moon Jae-in in May unveiled his plan for a global vaccine production hub https://www.reuters.com/world/asia-pacific/skoreas-covid-19-vaccine-shortages-overshadow-moon-biden-summit-2021-05-12 after agreeing with U.S. President Joe Biden on a partnership https://www.reuters.com/world/asia-pacific/south-koreas-moon-be-second-leader-second-asian-welcomed-by-biden-2021-05-21 that would combine U.S. expertise and South Korean production capacity.

In August, Moon said he would designate COVID-19 vaccines as one of three national strategic technologies, along with semiconductors and batteries, aiming to ramp up investment, give tax breaks and offer other incentives to help firms localise materials, parts and equipment.

https://www.marketscreener.com/quote/stock/HANMI-SCIENCE-CO-LTD-6493987/news/Private-S-Korea-firms-plan-5-4-billion-investment-to-create-vaccine-hub-36864915/

Allena Fast Tracked for Treatment of Hyperuricemia in Gout, Chronic Kidney Disease

 Novel oral therapeutic candidate ALLN-346 targets uric acid in the intestinal tract -

- Patients with gout and CKD have a serious condition with an unmet need for urate-lowering–therapies –

-Two Phase 2a studies currently enrolling patients with hyperuricemia and CKD -

- Initial bioactivity data expected in late 2021 or early 2022 -

https://finance.yahoo.com/news/allena-pharmaceuticals-receives-fast-track-120000047.html

Petros, Via Marketing Pact with Hims & Hers, Grows STENDRA Tablet Sales 476% in Year

 Petros Pharmaceuticals, Inc. (Petros, Nasdaq: PTPI), a leading provider of therapeutics for men's health, today announces a 476% growth year-over-year of STENDRA tablet sales as part of an exclusive digital health marketing agreement with Hims & Hers Health, Inc. ("Hims & Hers" or "Hims"), the multi-specialty telehealth platform focused on providing modern personalized health and wellness experiences to consumers. The companies also announce the availability of additional dosages of STENDRA through the Hims & Hers platform, further expanding the partnership.

"Our continued relationship with Hims supports an industry-leading telehealth platform that allows individuals to inquire about and address erectile dysfunction with discretion and by way of a convenient method of healthcare engagement," said Fady Boctor, Petros Pharmaceuticals' President and Chief Commercial Officer. "With significant growth year-over-year of STENDRA tablet sales through Hims, we are excited to expand our collaboration with Hims and enhance access to STENDRA through this critical channel."

STENDRA is currently FDA-approved in 50mg, 100mg and 200mg tablets, all of which are now accessible through the Hims platform. Consumers looking to purchase any prescription through Hims & Hers need to complete a virtual consultation with a licensed healthcare provider via the platform to see if a prescription treatment is medically recommended.

"Offering our customers access to STENDRA has helped to strengthen our platform and achieve our mission of providing greater access to personalized care," added Dr. Patrick Carroll, Chief Medical Officer at Hims & Hers. "We are elated to be able to provide help and support to the many people who experience erectile dysfunction. We look forward to expanding our relationship with Petros by providing more dosage options at affordable prices through our platform so that even more people can access high quality, personalized care."

"In our exclusive marketing agreement with Hims, Petros continues to support the goal of destigmatizing the request for this therapy and expanding overall engagement for treatment," concluded Mr. Boctor.

It is estimated that only about 25% of the approximately 30 million men suffering from erectile dysfunction in the U.S. have received oral erectile dysfunction therapy.

 https://finance.yahoo.com/news/petros-pharmaceuticals-inc-exclusive-marketing-131600621.html