BioLineRx Announces Submission of New Drug Application (NDA) to FDA for Motixafortide in Stem Cell Mobilization

BioLineRx Ltd.  announced the  submission of  its New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for Motixafortide in stem cell mobilization (SCM) for autologous bone marrow transplantation for multiple myeloma patients.

The NDA submission is based on the overwhelmingly positive top-line results from BioLineRx's GENESIS Phase 3 trial of Motixafortide on top of G-CSF (versus placebo on top of G-CSF) in stem cell mobilization for autologous bone marrow transplantation in multiple myeloma patients. The study met all primary and secondary endpoints with a very high degree of statistical significance (p<0.0001). The combination was also found to be safe and well tolerated.

"The submission of our first NDA is a significant milestone for our Company and gives us potential line of sight towards launching a product that we successfully developed for an indication in substantial need of more effective treatment options," stated Philip Serlin, Chief Executive Officer of BioLineRx. "Notably, ~90% of multiple myeloma patients in the GENESIS study went directly to transplantation after mobilizing the optimal number of stem cells following only one administration of Motixafortide and in only one apheresis session, compared to less than 10% of those receiving G-CSF alone. This high success rate has a substantial clinical benefit, especially when considering that new induction treatments are more effective than ever before but cause subsequent difficulty in mobilizing the target number of stem cells for transplantation. The high success rate may also confer significant benefits to transplant institutions through the more efficient use of apheresis units, where there is often a lack of available machines."

"The totality of data that we have compiled for Motixafortide in stem cell mobilization – both clinical and pharmacoeconomic – suggest that Motixafortide, if approved, can quickly become the key component of a new standard of care on top of G-CSF for all multiple myeloma patients undergoing autologous stem cell transplantation. The submission of our NDA brings us one critical step closer to that goal, and we look forward to working closely with the FDA during its review process," Mr. Serlin concluded.

The FDA's decision on acceptance of BioLineRx's NDA filing is expected in November. Assuming the filing is accepted, the potential PDUFA date would be in Q2 2023 (under a priority review process, if applicable) or Q3 2023 (under a standard review process). As BioLineRx finalizes its commercialization plans for Motixafortide in the U.S., the Company continues to advance critical pre-launch activities, required under any commercialization scenario, to ensure a robust and targeted commercial launch very soon after its PDUFA date, assuming FDA approval.

https://pubchem.ncbi.nlm.nih.gov/compound/Motixafortide

https://go.drugbank.com/drugs/DB14939

Cidara Therapeutics Announces FDA Acceptance for Priority Review of New Drug Application for Rezafungin for the Treatment of Candidemia and Invasive Candidiasis

Cidara Therapeutics, Inc.  , a biotechnology company developing long-acting therapeutics designed to improve the standard of care for patients facing serious diseases,  announced   the  FDA acceptance for filing and granted Priority Review to its New Drug Application (NDA) for rezafungin for the treatment of candidemia and invasive candidiasis. The FDA has assigned a Prescription Drug User Fee Act (PDUFA) target action date of March 22, 2023 enabled by rezafungin’s designation as a Qualified Infectious Disease Product (QIDP) and has indicated that it is currently planning to hold an advisory committee meeting to discuss the application. QIDP designation is reserved for antibacterial and antifungal drug candidates intended to treat serious or life-threatening infections. Rezafungin is a novel, once-weekly echinocandin antifungal being developed for the treatment of candidemia and invasive candidiasis, as well as for the prophylaxis of invasive fungal infections in patients undergoing allogeneic blood and marrow transplant.

“Today’s announcement is an important step forward for patients fighting difficult-to-treat and often deadly candidemia and invasive candidiasis, and represents a critical milestone for Cidara’s rezafungin development program,” said Jeff Stein, President, and CEO of Cidara Therapeutics. “The data generated across our Phase 2 and Phase 3 trials demonstrated that rezafungin could transform the current standard of care for the treatment of invasive Candida infections, and we are excited that rezafungin could potentially be the first new drug approved for this indication in over a decade.”

The NDA submission for rezafungin was supported by positive clinical data from the global ReSTORE Phase 3 and STRIVE Phase 2 clinical trials. Rezafungin dosed once-weekly demonstrated statistical non-inferiority versus caspofungin, the current standard of care, dosed once-daily, meeting the primary endpoints for both the FDA and the European Medicines Agency (EMA).

Cidara retains the rights to rezafungin in Japan and has licensed the commercial rights to Melinta Therapeutics in the U.S. and Mundipharma Medical in all other geographies.

About Rezafungin

Rezafungin is a novel once-weekly echinocandin being developed for both the treatment and prevention of serious fungal infections, such as candidemia and invasive candidiasis. The structure and properties of rezafungin are specifically designed to improve upon a clinically validated mechanism intended to enhance its efficacy and safety potential for patients. Cidara has completed a Phase 3 clinical trial with rezafungin for the first-line treatment of candidemia and/or invasive candidiasis (ReSTORE trial) and is currently conducting a second Phase 3 clinical trial of rezafungin for the prevention of invasive fungal disease in patients undergoing allogeneic blood and marrow transplantation (ReSPECT trial). Rezafungin has been designated a QIDP with Fast Track status by the FDA, and has been granted Orphan Drug Designation for its use in the treatment of invasive candidiasis in both the U.S. and EU.

Specific sequence of drugs reduces cost of treating metastatic breast cancer while preserving quality of life

The researchers developed three different computer models to predict how a hypothetical set of 10,000 patients with specific types of metastatic breast cancer would respond to different sequences and types of chemotherapy. For this study, the patient's cancer was either no longer responding to hormone therapies (endocrine resistant) or was a type of the disease called triple-negative breast cancer.

Currently, there are many chemotherapy choices to treat metastatic breast cancer. Oncologists have some preferences of which drugs to use early in treatment, but there is little clear evidence on the best order in which to give the drugs. The researchers consulted oncologists and experts in the field to choose which chemotherapy drugs were preferred choices to include in the study.

Mimicking clinical practice, and based upon existing data, the researchers then assumed that if a person started treatment with one drug, they would change to a second-choice treatment after their cancer stopped responding to the first drug, or if the side effects weren't tolerable. The purpose of the study was to test whether putting the drugs in one sequence compared to another could keep the patient on treatment for similar times while decreasing their side effect and/or cost burden.

"The cost of cancer drugs in the U.S. has rapidly increased, even for generics. As a society, we urgently need more strategies to reduce cancer drug costs without compromising outcomes, and our analysis provides quantifiable evidence to help providers choose lower priced, but equally effective sequences of drugs," said Stephanie B. Wheeler, PhD, MPH, professor of health policy & management at UNC Gillings and associate director of community outreach and engagement at UNC Lineberger and corresponding author of the article. "More spending on cancer care does not necessarily confer greater health benefits."

The costs calculated in this study were inclusive of medical and nonmedical costs borne by patients, including lost productivity. In this simulation, after two years, nearly all women would have completed the first three sets of treatment, but the cancer would cause the death of about one-third of the women. Productivity days lost due to sickness were similar across chemotherapy sequences, so most of the cost difference was due to drug savings. In the simulation, patients were placed in three groups, depending on what treatments they had already received for earlier episodes of breast cancer.

Outcomes in the three groups were:

• For people who had not previously received the common chemotherapy drug categories, including a taxane (e.g., paclitaxel) or an anthracycline (e.g., capecitabine), treatment with paclitaxel then capecitabine followed by doxorubicin corresponded to the highest expected gains in quality of life and lowest costs.
• For people who had previously received a taxane and an anthracycline drug, treatment with carboplatin, followed by capecitabine, followed by eribulin, corresponded to the highest expected gains in quality of life and lowest costs.
• For people who had previously received a taxane but not an anthracycline, treatment sequences beginning with capecitabine or doxorubicin, followed by eribulin, were most cost-effective.

"The drugs we studied are already recommended and reimbursed for the treatment of metastatic breast cancer, but the optimal sequencing of them has been unclear, which has led to considerable variation in physician preference and practice. Our study suggests that treatment sequencing approaches that minimize costs early may improve the value of care," Wheeler said. "The implications of this study are fairly straightforward for medical oncologists and those developing value-based clinical pathways to implement in practice now."

UNC Lineberger's Katherine E. Reeder-Hayes, MD, MBA, MSc, section chief of breast oncology and associate professor of medicine at UNC School of Medicine and one of the study's authors, said the treatment choices for metastatic breast cancer are constantly changing, and new options for targeted therapy have emerged even since this study was conducted. "Many oncologists and patients find that there aren't any more targeted therapies that fit the cancer's molecular profiles, so they are left with the choice of a number of chemotherapy drugs that may feel pretty similar or have an unclear balance of pros and cons.

"In that scenario, I hope our study will help expand the framework that we use to make these decisions from one where we just think about the biologic action of the drug to one where we also consider the bigger picture of what the treatment experience is like for the patient, including their financial burden, investment of time, and side effects," Reeder-Hayes added. "The most potent drug isn't always the next best choice depending on what the patient values and wants to accomplish with their treatment."

Looking ahead, the researchers have developed a financial navigation program to further support patients in managing the out-of-pocket costs of their cancer care. This program has been effective and well received by patients, caregivers and providers. The team is currently scaling up the intervention in nine rural and non-rural oncology practices across North Carolina to understand how well it works in different care settings. Cancer patients who need financial support managing the cost of their cancer care are being recruited for this undertaking.

Ref : https://ascopubs.org/doi/10.1200/JCO.21.02473

Drug turns cancer gene into 'eat me' flag for immune system

Sotorasib

The new therapy, described Sept. 12 in Cell Cancer, pulls a mutated version of the protein KRAS to the surface of cancer cells, where the drug-KRAS complex acts as an "eat me" flag. Then, an immunotherapy can coax the immune system to effectively eliminate all cells bearing this flag.

"The immune system already has the potential to recognize mutated KRAS, but it usually can't find it very well. When we put this marker on the protein, it becomes much easier for the immune system," said UCSF chemist and Howard Hughes Medical Institute Investigator Kevan Shokat, PhD, who helped lead the new work.

KRAS mutations are found in about one quarter of all tumors, making them one of the most common gene mutations in cancer. Mutated KRAS is also the target of sotorasib, which the Food and Drug Administration (FDA) has given preliminary approval for use in lung cancer, and the two approaches may eventually work well in combination.

"It's exciting to have a new strategy leveraging the immune system that we can combine with targeted KRAS drugs," said Charles Craik, PhD, a lead study author and professor of pharmaceutical chemistry at UCSF. "We suspect that this could lead to deeper and longer responses for cancer patients."

Turning Cancer Markers Inside Out

The immune system typically recognizes foreign cells because of unusual proteins that jut out of their surfaces. But when it comes to cancer cells, there are few unique proteins found on their outsides. Instead, most proteins that differentiate tumor cells from healthy cells are inside the cells, where the immune system can't detect them.

For many years, KRAS -- despite how common it is in cancers -- was considered undruggable. The mutated version of KRAS, which drives the growth of tumor cells, operates inside cells. It often has only one small change that differentiates it from normal KRAS and doesn't have a readily visible spot on its structure for a drug to bind. But over recent decades, Shokat carried out detailed analyses of the protein and discovered a hidden pocket in mutated KRAS that a drug could block. His work contributed to the development and approval of sotorasib.

Sotorasib, however, doesn't help all patients with KRAS mutations, and some of the tumors it does shrink become resistant and start growing again. Shokat, Craik and their colleagues wondered whether there was another way to target KRAS.

In the new work, the team shows that when ARS1620 -- a targeted KRAS drug similar to sotorasib -- binds to mutated KRAS, it doesn't just block KRAS from effecting tumor growth. It also coaxes the cell to recognize the ARS1620-KRAS complex as a foreign molecule.

"This mutated protein is usually flying under the radar because it's so similar to the healthy protein," says Craik. "But when you attach this drug to it, it gets spotted right away."

That means the cell processes the protein and moves it to its surface, as a signal to the immune system. The KRAS that was once hidden inside is now displayed as an "eat me" flag on the outside of the tumor cells.

A Promising Immunotherapy

With the shift of mutated KRAS from the inside to the outside of cells, the UCSF team was next able to screen a library of billions of human antibodies to identify those that could now recognize this KRAS flag. The researchers showed with studies on both isolated protein and human cells that the most promising antibody they had identified could bind tightly to the drug ARS1620 as well as the ARS1620-KRAS complex.

Then, the group engineered an immunotherapy around that antibody, coaxing the immune system's T cells to recognize the KRAS flag and target cells for destruction. They found that the new immunotherapy could kill tumor cells that had the mutated KRAS and were treated with ARS1620, including those that had already developed resistance to ARS1620.

"What we've shown here is proof of principle that a cell resistant to current drugs can be killed by our strategy," says Shokat.

More work is needed in animals and humans before the treatment could be used clinically.

The researchers say that the new approach could pave the way not only for combination treatments in cancers with KRAS mutations, but also other similar pairings of targeted drugs with immunotherapies.

"This is a platform technology," says Craik. "We'd like to go after other targets that might also move molecules to the cell surface and make them amenable to immunotherapy."

Ref : 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6965201/

https://en.wikipedia.org/wiki/Sotorasib

Smoking May Increase Odds of Meniere Disease in Men

For men, smoking is positively related and alcohol consumption is negatively related to the risk for Meniere disease (MD), according to a study published online Aug. 26 in the Journal of Clinical Medicine.

So Young Kim, Ph.D., from the CHA University in Seongnam, South Korea, and colleagues examined the association of smoking, alcohol consumption, and obesity with MD among the population older than 40 years of age in the Korean National Health Insurance Service-Health Screening Cohort from 2002 to 2019. A total of 15,208 MD patients were matched with 499,658 controls.

The researchers found that in the overall adult population, there was no association for smoking and alcohol consumption with MD. The odds of MD were lower in association with being underweight (adjusted odds ratio, 0.80; 95 percent confidence interval, 0.68 to 0.93; P = 0.004). Smoking was positively associated with MD in men, while there was a negative association observed for alcohol consumption with MD (adjusted odds ratios, 1.08 [95 percent confidence interval, 1.00 to 1.17; P = 0.043] and 0.87 [95 percent confidence interval, 0.81 to 0.94; P < 0.001], respectively).

"The current study improved previous knowledge on the associated factors of MD by concurrently assessing multiple lifestyle factors, including smoking, alcohol consumption, and obesity," the authors write. "As these are modifiable factors, lifestyle modifications can be clinically valuable management strategies for patients who suffer from MD."

Ref : For men, smoking is positively related and alcohol consumption is negatively related to the risk for Meniere disease (MD), according to a study published online Aug. 26 in the Journal of Clinical Medicine.

So Young Kim, Ph.D., from the CHA University in Seongnam, South Korea, and colleagues examined the association of smoking, alcohol consumption, and obesity with MD among the population older than 40 years of age in the Korean National Health Insurance Service-Health Screening Cohort from 2002 to 2019. A total of 15,208 MD patients were matched with 499,658 controls.

The researchers found that in the overall adult population, there was no association for smoking and alcohol consumption with MD. The odds of MD were lower in association with being underweight (adjusted odds ratio, 0.80; 95 percent confidence interval, 0.68 to 0.93; P = 0.004). Smoking was positively associated with MD in men, while there was a negative association observed for alcohol consumption with MD (adjusted odds ratios, 1.08 [95 percent confidence interval, 1.00 to 1.17; P = 0.043] and 0.87 [95 percent confidence interval, 0.81 to 0.94; P < 0.001], respectively).

"The current study improved previous knowledge on the associated factors of MD by concurrently assessing multiple lifestyle factors, including smoking, alcohol consumption, and obesity," the authors write. "As these are modifiable factors, lifestyle modifications can be clinically valuable management strategies for patients who suffer from MD."

Ref : Smoking May Increase Odds of Meniere Disease in Men 

Daily Multivitamin May Protect Against Cognitive Decline in Older Adults

In continuation of my update on Vitamin and their importance 

A daily multivitamin may provide cognitive benefits for older adults, according to a study published online Sept. 14 in Alzheimer’s & Dementia.

Laura D. Baker, Ph.D., from the Wake Forest University School of Medicine in Winston-Salem, North Carolina, and colleagues assessed whether daily use of cocoa extract (containing 500 mg/day flavanols) versus placebo and a commercial multivitamin-mineral (MVM) versus placebo improved cognition in 2,262 older women and men (mean age, 73 years).

The researchers found that cocoa extract had no effect on global cognition. However, compared with placebo, daily MVM supplementation resulted in a statistically significant benefit on global cognition, with a more pronounced effect seen in participants with a history of cardiovascular disease. Benefits of MVM were also seen for memory and executive function. There were no significant interactions observed between cocoa extract and MVM for any of the cognitive composites.

"Our study showed that although cocoa extract did not affect cognition, daily multivitamin-mineral supplementation resulted in statistically significant cognitive improvement. This is the first evidence of cognitive benefit in a large longer-term study of multivitamin supplementation in older adults," Baker said in a statement. "It's too early to recommend daily multivitamin supplementation to prevent cognitive decline. While these preliminary findings are promising, additional research is needed in a larger and more diverse group of people."

Ref : Daily Multivitamin May Protect Against Cognitive Decline in Older Adults 

FDA Approves Zoryve (roflumilast) Cream for the Treatment of Plaque Psoriasis

 

 

 

Arcutis Biotherapeutics, Inc.   an early commercial-stage biopharmaceutical company focused on developing meaningful innovations in immuno-dermatology, announced the U.S. Food and Drug Administration (FDA)   approval of the  the New Drug Application (NDA) for Zoryve (roflumilast) cream 0.3% for the treatment of plaque psoriasis, including intertriginous areas, in patients 12 years of age or older. The first and only topical phosphodiesterase-4 (PDE4) inhibitor approved for the treatment of plaque psoriasis, Zoryve provides rapid clearance of psoriasis plaques and reduces itch in all affected areas of the body. Zoryve — a once-daily, steroid-free cream in a safe and well tolerated, patient-friendly formulation — is uniquely formulated to simplify disease management for people living with plaque psoriasis.

“Today Arcutis has reached a major milestone, with our ability to offer this next generation topical PDE4 inhibitor to both adults and adolescents with plaque psoriasis. Zoryve’s combination of efficacy, safety, and tolerability, coupled with our proprietary HydroARQ Technology formulation, is designed to fit into patients’ everyday lives with no restrictions on duration of use,” said Frank Watanabe, President and CEO of Arcutis. “Additionally, Zoryve has been shown to rapidly clear plaques and reduce itch across all areas of the body. Zoryve is the only topical for which data focused on the treatment of intertriginous plaques — a common area affected by plaque psoriasis — have been specifically generated. This FDA approval is the fruition of our efforts, and we are excited to launch Zoryve, with expected product availability by mid-August.”

Topical therapies remain the primary treatment option for the vast majority of individuals with plaque psoriasis, a common immune-mediated skin disease that affects approximately nine million people in the U.S. and is the most frequent type of psoriasis occurring in both adults and adolescents. Severity can range between mild, moderate, and severe, with itch being the most burdensome and frequently reported symptom.

While the disease may affect any area of the body, plaques in certain areas, like the face, elbows and knees, genitalia, and intertriginous areas (areas of skin-to-skin contact), present unique treatment challenges. As a result, individuals with psoriasis are often prescribed multiple topical medications for different areas, which makes for a complicated treatment regimen.

“In multiple clinical trials, Zoryve was proven to be safe and effective, with improvements in disease clearance in hard-to-treat areas like knees and elbows, as well as in sensitive areas such as the face, genitalia, and intertriginous areas. Zoryve is very well tolerated, which is an important consideration for treating a chronic skin disease such as plaque psoriasis,” said Mark Lebwohl M.D., FAAD, principal investigator and Dean for Clinical Therapeutics and Chairman Emeritus of the Kimberly and Eric J. Waldman Department of Dermatology at the Icahn School of Medicine at Mount Sinai. “With this FDA approval, adults and adolescents with psoriasis and their dermatologists have a new steroid-free treatment option for use on all affected areas of the body.”

Zoryve features HydroARQ Technology™, a proprietary drug delivery formulation that creates a non-greasy moisturizing cream that spreads easily and absorbs quickly.

“Plaque psoriasis is a challenging disease and finding the right treatment option can be complicated, especially if individuals have to use multiple treatments for different parts of their body. We welcome a new treatment option that can make a meaningful difference for adults and adolescents with plaque psoriasis,” says Leah M. Howard, President and CEO of the National Psoriasis Foundation. “Our hope is that new treatments translate into improved outcomes and help alleviate the burdens of chronic disease for people impacted by psoriasis.”

Arcutis intends to make Zoryve widely available via key wholesaler and national dermatology pharmacy channels as a new treatment option by mid-August, and the Company is dedicated to affordable access to therapy. The Zoryve Direct patient support program will help commercially insured individuals with plaque psoriasis get access and start Zoryve treatment as prescribed by their healthcare provider quickly and easily by helping them navigate the payer process, lowering the out-of-pocket cost for eligible patients, and offering programs that support staying on therapy.^† Arcutis will also offer the Arcutis Cares patient assistance program (PAP) – the first of its kind for a topical psoriasis treatment – that will provide Zoryve at no cost for financially eligible patients who are uninsured or underinsured.^‡

With this approval, Arcutis has access to, and plans to draw, an additional $125 million tranche as part of the Company’s non-dilutive financing agreement with SLR Capital Partners. Combined with the Company’s cash, cash equivalents, restricted cash, and marketable securities as of June 30, 2022, this additional $125 million will provide for capital resources of over $400 million to support the launch and commercialization efforts for Zoryve, as well as continue to advance the Company’s pipeline development initiatives.

 

 Ref : https://en.wikipedia.org/wiki/Roflumilast