Spectrum PDUFA date Sept. 9

 Eflapegrastim BLA under FDA review; PDUFA date September 9, 2022

FDA completes re-inspection of drug substance manufacturing facility for eflapegrastim

Poziotinib NDA under FDA review with ODAC meeting on September 22, 2022

Management to host webcast and conference call today at 8:30 a.m. ET / 5:30 a.m. PT

Conference Call

Thursday, August 11, 2022 @ 8:30 a.m. Eastern/5:30 a.m. Pacific

To access the live call by phone, please go to this link (registration link), and you will be provided with dial in details. To avoid delays, participants are encouraged to dial into the conference call fifteen minutes ahead of the scheduled start time.

This conference call will also be webcast. Listeners may access the webcast, which will be available on the investor relations page of Spectrum Pharmaceuticals' website: https://investor.sppirx.com/events-and-presentations on August 11, 2022 at 8:30 a.m. Eastern/5:30 a.m. Pacific.

https://finance.yahoo.com/news/spectrum-pharmaceuticals-reports-second-quarter-120000882.html

Centessa Left with Two Clinical Assets after Second Development Program Halted

 Boston-based Centessa Pharmaceuticals announced Wednesday that it is discontinuing the development of ZF874 for Alpha-1 Antitrypsin Deficiency (AATD), an inherited disorder that can lead to lung and liver disease development, two months after halting another asset, lixivaptan. 

As could be expected, the news was not met with happiness from investors, who began to dump the company stock. Shares of Centessa fell more than 5% in afternoon trading to close at $4.75.

The company halted development of ZF874 following the report of an adverse event that involved elevated liver enzymes in a patient dosed with 5 mg of the experimental treatment during a Phase I study. This was the second such event. Last year, in the first cohort of the Phase I study, a patient experienced elevated enzymes following a higher dose of 15 mg. 

ZF874 is a pharmacological chaperone designed to rescue the folding of the Z variant of alpha-1-antitrypsin. Not only did the two patients experience the adverse events, but, based on data observed in the study, Centessa has concluded that ZF874 was unlikely to achieve the desired target product profile.

Saurabh Saha, chief executive officer of Centessa, said the decision to discontinue the study is disappointing news for the A1AT patient community. Saha said the company will continue to analyze data from the Phase I study in order to inform future developmental programs for other compounds in its pipeline. Saha added that Centessa continues to believe the "pharmacological chaperone approach has the potential to address both the lung and liver manifestations of AATD."

In June, the company, which launched last year following the merger of 10 private biotech companies, scrapped the development of lixivaptan due to similar safety concerns. The company noted alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevations in one subject who participated in the open-label ALERT study. 

At the time, Centessa said its decision to halt development was based on a "thorough reassessment of the commercial potential of lixivaptan," which was being studied in Phase III for APKD, a genetic, progressive disorder characterized by the growth of numerous cysts in the kidneys. Typically, symptoms for APKD include kidney cysts, pain in the back, the sides and headaches. Other symptoms include liver and pancreatic cysts, urinary tract infections, abnormal heart valves, high blood pressure, kidney stones and brain aneurysms.

With the halt of development for lixivaptan and ZF874, Centessa is left with two clinical assets in its pipeline. SerpinPC, an activated protein C inhibitor, is in mid-stage development for hemophilia A and B. The company's other clinical-stage candidate is CBS001, an anti-LIGHT monoclonal antibody in development for inflammatory and fibrotic diseases. CBS001 is currently in Phase I.

Centessa has other preclinical programs, including the anti-BDCA1 monoclonal antibody CBS004 for autoimmune diseases and checkpoint inhibitors LB101 and LB201, which are expected to be assessed against undisclosed solid tumors.

"We remain on track to initiate registrational studies for SerpinPC for the treatment of Hemophilia B in the second half of this year and look forward to initiating clinical trials with LB101 for solid tumors, after our planned IND filing late this year," Saha continued in his statement. "Beyond these, we are continuing to advance our earlier stage programs and expect multiple clinical proof of concept readouts across our pipeline over the next two years. Importantly, with a world-class R&D team and cash runway that extends into 2026, we are exceptionally well positioned to deliver on these goals."

Centessa reported cash and cash equivalents of $484.2 million as of June 30.

https://www.biospace.com/article/centessa-halts-second-clinical-program-in-two-months-due-to-safety-concerns/

Facing Thousands of Zantac-Related Lawsuits, GSK and Sanofi See Mass Sell-Off

 The makers of ranitidine-based products, such as Sanofi’s Zantac, are reeling from multiple lawsuits related to carcinogenic contamination of products that could result in billions of dollars in damages.

With those payouts on the line, investors have begun a mass sell-off of shares of Sanofi US, GlaxoSmithKline and Haleon, the makers of the ranitidine-based products that contain known carcinogens. Shares of Sanofi have fallen more than 20% in two days, while GSK is down 12% and Haleon, its consumer goods spinoff that launched this year, is down 13%, Bloomberg reported. Combined, the losses total about $40 billion in market share.

Multiple lawsuits are winding their way through the courts, including one in Illinois that is set for late August. Other trials are expected to begin in the first few months of 2023.

Plaintiffs are suing the companies over allegations that the known carcinogens within the ranitidine-based products, particularly N-nitrosodimethylamine (NDMA), have contributed to the development of cancer. The lawsuits echo similar litigations against Bayer and its subsidiary Monsanto for carcinogens in the weed killer Roundup that plaintiffs allege led to their own cancer diagnoses.

GSK, Haleon and Sanofi, as well as Pfizer, which sold ranitidine for a short period, could face up to $45 billion in damages. In a Thursday note, Deutsche Bank analyst Emmanuel Papadakis warned that the ranitidine legal issues “are likely to act as a short-term headwind for both GSK and Sanofi shares,” Bloomberg said.

The Potential Risks of Ranitidine

Two years ago, the U.S. Food and Drug Administration called for the removal of ranitidine-based products due to the risks of contamination. The regulatory agency conducted an investigation into the potential contamination. In its 2020 findings, the FDA said the impurity in some ranitidine products increases over time and when stored at higher than room temperatures. The regulator also said they may result in consumer exposure to unacceptable levels of this impurity, BioSpace previously reported.

Prior to that call from the FDA, Sanofi and GSK had already removed some lots of ranitidine-based products from the shelves when the issue was first reported in the fall of 2019.

Ranitidine is an H2 (histamine-2) blocker. It is designed to reduce the amount of acid in the stomach. Zantac was the most popular version of this medication sold in pharmacies throughout the world. Investigations of the drug revealed NDMA was found in the product.

NDMA is a known environmental contaminant and is found in water and foods, including meats, dairy products and vegetables. In large amounts, NDMA can cause health problems, but the FDA said the levels it initially found in ranitidine were low. However, with concerns that the levels could increase over time while in storage, the prudent thing to do was remove them from the market.

Sanofi Downplays Risks of Litigation 

NDMA contamination isn’t limited to ranitidine. The FDA has previously issued warnings about NDMA contamination in various blood pressure treatments. Those concerns led to companies like Teva Pharmaceuticals issuing a recall of bulk Losartan Potassium after NDMA was discovered in the manufacturing process.

While none of the three companies replied to Bloomberg’s request for comment on the litigation, last month, France-based Sanofi, facing more than 70,000 complaints, downplayed the risks of litigation during its earnings call. Company officials said there is “no reliable evidence” that its Zantac product, at one time the best-selling medicine, causes cancer. Sanofi suggested that plaintiffs will have a difficult time proving their case in court, Bloomberg reported.

Last year, there was public outcry over allegations of deleted emails at Sanofi that plaintiffs say could have shown the company knew about the carcinogens but chose to ignore them to protect sales. Sanofi was conducting an internal investigation into the loss of emails, many of which are alleged to have been tied to Michael Bailey, the former head of regulatory affairs for Sanofi’s U.S. Consumer Healthcare division. Bailey is now head of scientific affairs for North America in the company’s consumer health business.

Prior to its official spinout from GSK, Haleon noted it has “certain indemnification obligations to GSK and Pfizer” related to ranitidine and other potential issues. Because of this, some analysts suggest Haleon’s role in litigation will be limited, Bloomberg reported.

https://www.biospace.com/article/facing-thousands-of-zantac-related-lawsuits-gsk-and-sanofi-face-mass-sell-off-of-shares/

Virios corporate update

 

• Completed patient dosing in Phase 2b FORTRESS fibromyalgia study

• Top line FORTRESS results expected in September 2022

https://finance.yahoo.com/news/virios-therapeutics-announces-second-quarter-110500799.html

Bionano Publishes on Using OGM for Detection of Repeat Expansions in CANVAS and Adult-Onset Ataxia

 Bionano Genomics, Inc. (Nasdaq: BNGO) today announced the publication of the first study to evaluate the utility of optical genome mapping (OGM) in the analysis of repeat expansion disorders. Repeat expansion disorders are a class of disorders that impact approximately 1 in 3,000 people and are caused by expansions of short tandem DNA repeats.

Researchers in this study describe how OGM can be adopted as an alternative to Southern blot analysis for the identification of repeat expansions in the RFC1 gene that lead to cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS) and adult-onset ataxia in multiple populations. Individuals with RFC1 (AAGGG)n repeat expansion disorder may present with a spectrum of features including cerebellar ataxia, neuropathy, and vestibular areflexia. Specifically, ataxias are a group of neurodegenerative repeat expansion disorders, characterized by atrophy of the cerebellum that leads to the inability to control balance and coordination. Even though there are many known cerebellar ataxia–causing genes and variations, some adult patients with adult-onset ataxia remain genetically undiagnosed, and studies to identify genetic causes are ongoing.

In the study, researchers screened 626 samples for the presence of (AAGGG)n repeat expansions in the RFC1 gene using a combination of PCR to detect repeat sequences, and OGM, to determine the size of the repeat expansions. OGM confirmed the presence of expanded RFC1 alleles in all cases where it was used as part of the workflow. Repeats identified using OGM were in the range of 800–1299 repeat units. OGM is well-suited for analyzing large repeat expansion disorders that require the measurement of long, intact DNA molecules for accurate sizing, as was observed in this study. The study noted the successful use of OGM to replace the labor intensive and time-consuming Southern blot, which has been the “gold” standard for sizing repeat expansions up to now.

https://finance.yahoo.com/news/bionano-genomics-announces-first-publication-120000534.html

Veru: Progresses Sabizabulin Treatment for COVID Towards Regulatory Decisions

 -Sabizabulin for COVID-19 Emergency Use Authorization Application Submitted to U.S. FDA in June 2022--

--The UK’s Medicines and Healthcare Products Regulatory Agency Informed the Company that its Sabizabulin Marketing Authorization Application Will Receive Expedited Review--

--European Medicines Agency’s Emergency Task Force Initiated Review of Sabizabulin Treatment for Hospitalized COVID Patients for Emergency Use in European Union Countries--

--The New England Journal of Medicine Evidence® Published Phase 3 Clinical Trial Results Demonstrating that Sabizabulin Treatment Significantly Reduced Deaths in High-Risk Hospitalized COVID-19 Patients--

--Company Prepares for U.S. and Ex-U.S. Commercial Launches if Emergency Authorizations Are Granted--

--Company to Host Investor Conference Call Today at 8 AM ET--

Interested parties may access the call by dialing 1-800-341-1602 from the U.S. or 1-412-902-6706 from outside the U.S. and asking to be joined into the Veru Inc. call. The call will also be available through a live, listen-only audio broadcast via the Internet at www.verupharma.com. Listeners are encouraged to visit the website at least 10 minutes prior to the start of the scheduled presentation to register, download and install any necessary software. A playback of the call will be archived and accessible on the same website for at least three months. A telephonic replay of the conference call will be available, beginning the same day at approximately 12 p.m. (noon) ET by dialing 1-877-344-7529 for U.S. callers, or 1-412-317-0088 from outside the U.S., passcode 1902173, for one week.

https://finance.yahoo.com/news/veru-reports-third-quarter-fiscal-103000236.html

Revance slapped with another FDA citation, putting approval hopes for Botox rival in limbo

 One year and another FDA inspection later, Revance has been hit with a second round of manufacturing citations, adding another wrinkle to its approval bid for a potential Botox rival.

After an FDA visit last summer yielded a Form 483, the FDA completed its re-inspection of Revance’s production facility in July, the company said in a recent investor report. The good news is the FDA closed out the original five observations it made in 2021. The bad news? The FDA slapped Revance with another Form 483, this time outlining three separate issues.

Revance says it has “already provided its responses” and feels “confident” about the adjustments it’s proposed.

Still, the FDA rebuke bodes ill for the near-term approval DaxibotulinumtoxinA—Revance’s would-be rival to AbbVie’s Botox—which is up for a potential U.S. green light by Sept. 8.

In the latest Form 483, the FDA’s first observation covers failures to consistently respond to deviations of standard operating procedures. The second centers on the company's operation and cleaning of filtration equipment. In the third observation, the FDA said Revance failed to include a redundant site for working cell bank storage in its application.

Revance’s regulatory path for DaxibotulinumtoxinA has been riddled with potholes. Before the company earned its first Form 483 last year, COVID-19 restrictions delayed a 2020 inspection of the company’s Newark, California plant, forcing Revance to wait on an approval decision.

Things came to a head last July, however, when the FDA handed down five observations regarding quality control measures and record-keeping.

In October 2021, Revance said it had responded to the issues and still expected an FDA approval by the end of 2021. 

Aside from Revance's regulatory ordeals, the company is battling a patent lawsuit from Botox maker AbbVie. A Revance spokesperson last year said it believes the patents at issue "are not infringed upon by Revance or our supply source partner Ajinomoto or are invalid."

The FDA is weighing DaxibotulinumtoxinA for approval as an injection for frown lines, which is one of Botox’s approved aesthetic uses. 

Last year, AbbVie’s Botox generated $2.2 billion in its aesthetic uses.

https://www.fiercepharma.com/manufacturing/something-frown-about-revance-slapped-another-fda-citation-putting-approval-hopes