Novo Nordisk announces FDA approval of Tresiba (insulin degludec injection) for diabetes treatment

Novo Nordisk, a world leader in diabetes care, today announced that the U.S. Food and Drug Administration (FDA) approved the new drug application for Tresiba® (insulin degludec injection), a once-daily, long-acting basal insulin. Tresiba® is indicated for use alone, or in combination with oral antidiabetic medicines or bolus insulin, and is approved for glycemic control in adults with type 1 and type 2 diabetes. Tresiba® provides a long duration of action beyond 42 hours. While patients are encouraged to take their insulin at the same time each day, Tresiba® allows patients to dose at any time of the day.

"Since 1923, Novo Nordisk has been committed to advancing insulin therapy for patients with diabetes, and we are proud to bring forward the first new basal insulin molecule to be approved by the FDA in 10 years," said Jesper Høiland, president of Novo Nordisk in the U.S. and executive vice president of Novo Nordisk A/S. "Novo Nordisk is excited to launch Tresiba® in the United States in the first quarter of 2016."

Ref : http://www.diapedia.org/management/insulin-degludec 

Novo Nordisk announces FDA approval of Tresiba (insulin degludec injection) for diabetes treatment

Allergan releases generic INVEGA (paliperidone extended-release tablets) in the U.S.

In continuation oof my update on paliperidone

Allergan plc (NYSE: AGN), a leading global pharmaceutical company, today announced that it has launched a generic version of Janssen's INVEGA® (paliperidone extended-release tablets) in the U.S. Allergan is the first company to receive FDA approval for and launch a generic version of INVEGA®, demonstrating the deep expertise of the Company's global generics R&D, regulatory and supply chain teams.

"This launch reinforces Allergan's commitment to developing, manufacturing and bringing to market high-quality, affordable versions of challenging products like INVEGA®, benefiting patients and reducing healthcare costs," said Robert Stewart, Allergan's Executive Vice President & President, Generics and Global Operations.

INVEGA® extended-release tablets are indicated for the treatment of schizophrenia in adults and adolescents (12-17 years of age).

For the 12 months ended July 31, 2015, INVEGA® had total U.S. brand sales of approximately $612 million, according to IMS Health data.

Allergan releases generic INVEGA (paliperidone extended-release tablets) in the U.S.

TUM scientists develop molecules that could pave way for new treatments to fight Alzheimer's, diabetes

When proteins change their structure and clump together, formation of amyloid fibrils and plaques may occur. Such 'misfolding' and 'protein aggregation' processes damage cells and cause diseases such as Alzheimer's and type 2 diabetes. A team of scientists from the Technical University of Munich (TUM) headed by Professor Aphrodite Kapurniotu have now developed molecules that suppress protein aggregation and could pave the way for new treatments to combat Alzheimer's, type 2 diabetes and other cell-degenerative diseases.

The scientists designed and studied 16 different peptide molecules in order to find out which of them are able to impede the 'clumping' of the proteins amyloid beta (Aß) and islet amyloid polypeptide (IAPP), which are associated with Alzheimer's and type 2 diabetes.

The molecules were designed on the basis of scientific work that shows that the Aß and IAPP proteins interact with each other, and that this 'cross-amyloid interaction' suppresses their clumping. The researchers selected short sequences of the IAPP protein that correspond to the key regions involved in the interaction with the Alzheimer's protein. These "hot segments" were then chemically linked to each other by using specific peptide segments as 'linkers' in order to mimic and optimize the IAPP cross-amyloid interaction surface.

Ref : http://www.tum.de/en/about-tum/news/press-releases/short/article/32611/

TUM scientists develop molecules that could pave way for new treatments to fight Alzheimer's, diabetes

SMC approves Bayer's Xofigo for treatment of castration-resistant prostate cancer in NHS Scotland

The Scottish Medicines Consortium (SMC) has today announced that Xofigo® (radium-223 dichloride) has been accepted for use within NHS Scotland for the treatment of adult patients with castration-resistant prostate cancer (CRPC), symptomatic bone metastases and no known visceral metastases.

While the National Institute for Health and Care Excellence (NICE) has published draft guidance recommending radium-223 dichloride in advanced prostate cancer, this does not cover all patients and may not be confirmed for a number of months and could change. In Scotland, under SMC guidance clinicians will have the choice to use Xofigo prior to chemotherapy or after. So while patient access has improved in Scotland, it is worsening in the rest of the UK.

“This is a positive step for advanced prostate cancer patients in Scotland. However, the picture in England, Wales and Northern Ireland is very different. Historically radium-223 dichloride has been available only in England, funded through the Cancer Drugs Fund (CDF). This CDF funding is due to cease later this year following the recent CDF delisting round,” said Mr Hugh Gunn, Tackle Prostate Cancer. “If NICE pass radium-223 dichloride for use, this will be for post chemotherapy patients only. This will prevent the use of radium-223 dichloride in men who, for one reason or another do not progress to chemotherapy.”

SMC approves Bayer's Xofigo for treatment of castration-resistant prostate cancer in NHS Scotland

Patients with advanced kidney cancer benefit from cabozantinib treatment

In continuation of my update on cabozantinib

Patients with advanced kidney cancer live for nearly twice as long without their disease progressing if they are treated with cabozantinib, a drug that inhibits the action of tyrosine kinases - enzymes that function as an "on" or "off" switch in many cellular processes, including cancer.

In the second of two late-breaking presentations of research that is predicted to change the way kidney cancer patients are treated, Professor Toni Choueiri will tell the presidential session of the 2015 European Cancer Congress, about results from the first 375 patients out of a total of 658 patients recruited to the phase III clinical METEOR trial comparing cabozantinib with everolimus, the current standard treatment for the disease.

Analysis of results in July 2015 showed that the estimated median (average) progression-free survival time for patients with advanced clear cell kidney cancer, randomised to receive cabozantinib, was 7.4 months, while it was 3.8 months for those receiving everolimus. The objective response rate (the proportion of patients whose tumours shrank, assessed up to 17 months) was 21% for cabozantinib and 5% for everolimus.

An interim analysis of overall survival among all of the 658 patients found that it was a third better for patients receiving cabozantinib. The findings are published simultaneously with the ECC2015 presentation in the New England Journal of Medicine.

Prof Choueiri, who is Associate Professor of Medicine at Harvard Medical School and Clinical Director and Kidney Cancer Center Director at The Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, USA, said: "I am very excited about the outcome of the study since the results may change the standard of care in patients with advanced kidney cancer who have received prior standard therapy that targets the vascular endothelial growth factor receptor (VEGFR).

"Although treatment with VEGFR-targeted drugs has been very effective in the first line of therapy for patients with advanced kidney cancer, in many cases tumour cells find ways to escape control by these drugs. Cabozantinib is a new drug that targets possible escape mechanisms of tumour cells, including the tyrosine kinases MET, VEGFR and AXL. The results of the METEOR trial indicate that cabozantinib is able to shrink tumours and slow down tumour growth much better than current standard treatment in patients who previously received VEGFR-targeted drugs. This has resulted in a significant reduction in the rate of disease progression or death in the cabozantinib arm as compared with the everolimus arm. Regaining tumour control after prior targeted therapy may reduce symptoms related to kidney cancer and eventually help patients live longer.

Patients with advanced kidney cancer benefit from cabozantinib treatment

Dried plum diet may help reduce colon cancer risk

Researchers from Texas A&M University and the University of North Carolina have shown a diet containing dried plums can positively affect microbiota, also referred to as gut bacteria, throughout the colon, helping reduce the risk of colon cancer.

The research was funded by the California Dried Plum Board and presented at the 2015 Experimental Biology conference in Boston.

"Through our research, we were able to show that dried plums promote retention of beneficial bacteria throughout the colon, and by doing so they may reduce the risk of colon cancer," said Dr. Nancy Turner, Texas A&M AgriLife Research professor in the nutrition and food science department of Texas A&M University, College Station.

According to the American Cancer Society, colon cancer is the third leading cause of cancer-related deaths in the U.S. when men and women are considered separately, and the second-leading cause when the figures are combined. During 2015, colon cancer is expected to cause about 49,700 deaths nationwide.

A good amount of research has already shown that one's diet can alter the metabolism and composition of colon microbiota, which has major implications for disease prevention and treatment, Turner said.

She said there are trillions of bacteria in the intestinal tract and so far more than 400 individual species have been identified. Previous research has shown that disruptions to the microbiota are involved in the initiation of intestinal inflammation and recurrence of inflammatory bouts that can promote development of colon cancer.

"Our research explored the potential cancer-protective properties of dried plums using a well-established rat model of colon cancer," she said. "Dried plums contain phenolic compounds, which have multiple effects on our health, including their ability to serve as antioxidants that can neutralize the oxidant effect of free radicals that can damage our DNA.

"The hypothesis we tested in this experiment was that consumption of dried plums would promote retention of beneficial microbiota and patterns of microbial metabolism throughout the colon. If it did this, then it might also help reduce the risk of colon cancer."

Dried plum diet may help reduce colon cancer risk

The Nobel Prize in Chemistry 2015

The cells’ toolbox for DNA repair

The Nobel Prize in Chemistry 2015 is awarded to Tomas Lindahl, Paul Modrich and Aziz Sancar for having mapped, at a molecular level, how cells repair damaged DNA and safeguard the genetic information. Their work has provided fundamental knowledge of how a living cell functions and is, for instance, used for the development of new cancer treatments.

Each day our DNA is damaged by UV radiation, free radicals and other carcinogenic substances, but even without such external attacks, a DNA molecule is inherently unstable. Thousands of spontaneous changes to a cell’s genome occur on a daily basis. Furthermore, defects can also arise when DNA is copied during cell division, a process that occurs several million times every day in the human body.

The reason our genetic material does not disintegrate into complete chemical chaos is that a host of molecular systems continuously monitor and repair DNA. The Nobel Prize in Chemistry 2015 awards three pioneering scientists who have mapped how several of these repair systems function at a detailed molecular level.

In the early 1970s, scientists believed that DNA was an extremely stable molecule, but Tomas Lindahl demonstrated that DNA decays at a rate that ought to have made the development of life on Earth impossible. This insight led him to discover a molecular machinery, base excision repair, which constantly counteracts the collapse of our DNA.

Aziz Sancar has mapped nucleotide excision repair, the mechanism that cells use to repair UV damage to DNA. People born with defects in this repair system will develop skin cancer if they are exposed to sunlight. The cell also utilises nucleotide excision repair to correct defects caused by mutagenic substances, among other things.

Paul Modrich has demonstrated how the cell corrects errors that occur when DNA is replicated during cell division. This mechanism, mismatch repair, reduces the error frequency during DNA replication by about a thousandfold. Congenital defects in mismatch repair are known, for example, to cause a hereditary variant of colon cancer.

The Nobel Laureates in Chemistry 2015 have provided fundamental insights into how cells function, knowledge that can be used, for instance, in the development of new cancer treatments.

The Nobel Prize in Chemistry 2015

S1 Biopharma supports FDA's approval of flibanserin for women living with HSDD

Approval of flibanserin by the U.S. Food and Drug Administration (FDA) was a significant advancement for women's health, addressing the important unmet medical need for women living with HSDD. The condition is marked by a lack of sexual thoughts and desire for sexual activity that cannot be accounted for by another medical, physical, psychiatric, or medication-induced condition. An estimated one in 10 women may have HSDD at some point in their life, for which therapies like flibanserin and Lorexys, S1 Biopharma's next-generation first in class drug, are being developed to address.

We are pleased for Dr. Robert Pyke, who before joining S1 Biopharma as Chief Medical Officer in 2012 to develop Lorexys, had fathered flibanserin at Boehringer Ingelheim before it was acquired by Sprout Pharmaceuticals.

S1 Biopharma, Inc. is continuing the development of Lorexys, a unique multi-receptor oral tablet being studied for the treatment of HSDD in pre-menopausal women. Lorexys will provide first-line treatment for women suffering from HSDD as an easy to administer daily pill.

S1 Biopharma supports FDA's approval of flibanserin for women living with HSDD

STA inks license and commercialisation agreement with PharmaMar for APLIDIN (plitidepsin)

Australian biopharmaceutical company Specialised Therapeutics Australia has struck an exclusive license and commercialisation agreement with European pharmaceutical partner company PharmaMar to market and distribute the novel oncology drug APLIDIN® (plitidepsin) in Australia and New Zealand.

Under the terms of the agreement, PharmaMar will receive an upfront payment, royalties and additional remunerations for regulatory and sales milestones achieved by APLIDIN® (plitidepsin).

PharmaMar will retain production rights and will supply the finished product to STA for exclusive commercial use in Australia and New Zealand.

APLIDIN® (plitidepsin) is PharmaMar´s second anticancer drug candidate obtained from a marine organism. This first in class drug is currently in development for the treatment of multiple myeloma and a type of T cell lymphoma. The company announced in June that patient recruitment of the international pivotal Phase III trial (ADMYRE) for APLIDIN® (plitidepsin) in refractory/relapsed multiple myeloma was successfully completed.

STA inks license and commercialisation agreement with PharmaMar for APLIDIN (plitidepsin)

AbbVie's venetoclax Phase 2 trial meets primary endpoint in patients with relapsed/refractory CLL with 17P deletion

 

AbbVie (NYSE: ABBV), a global biopharmaceutical company, announced that a Phase 2 trial of its investigational medicine
venetoclax met its primary endpoint of achieving overall response ratesin patients with relapsed/refractory or previously untreated chroniclymphocytic leukemia (CLL) with 17p deletion, according to anindependent review analysis. The open-label study evaluated the efficacy and safety of venetoclax, an inhibitor of the B-cell lymphoma-2 (BCL-2)
protein that is being developed in partnership with Genentech and Roche.

Data from this study will be presented at an upcoming medical conference and will serve as the pivotal registration data forapplications to the FDA, EMA and other health authorities. The safety profile was similar to previous studies and no unexpected safety signals were reported for venetoclax.

AbbVie's venetoclax Phase 2 trial meets primary endpoint in patients with relapsed/refractory CLL with 17P deletion

Envarsus XR granted FDA orphan drug designation for prophylaxis of organ rejection in kidney transplant patients

Veloxis Pharmaceuticals A/S (OMX: VELO), today announced that Envarsus^® XR was     granted Orphan Drug status by the U.S. Food and Drug Administration(FDA) for prophylaxis of organ rejection in patients who convert fromimmediate-release tacrolimus. Envarsus^® XR received marketing authorization from the FDA on July 10, 2015.

"We view Orphan Drug status as the FDA's recognition of thedifferentiated profile and the unique 'switch' indication of Envarsus^® XR compared  to  other               tacrolimus products," said William Polvino, M.D.,
president and chief executive officer of Veloxis. "We now look forwardto making Envarsus^® XR available to conversion patients by the end of 2015."

Orphan drug designation is designed is to encourage the developmentof drugs that may provide significant benefit to patients suffering from rare diseases. The designation is granted by the FDA upon recognition
that the prevalence of the U.S. target patient population is 200,000patients or less. Orphan drug designation entitles Veloxis to a waiver of the FDA prescription drug user fees for Envarsus^® XR aswell as for potential tax incentives. Additionally, U.S. dataexclusivity protection may be extended for up to seven years.

 

Envarsus XR granted FDA orphan drug designation for prophylaxis of organ rejection in kidney transplant patients

AbbVie's venetoclax Phase 2 trial meets primary endpoint in patients with relapsed/refractory CLL with 17P deletion

Venetoclax, also known as ABT-199 or GDC0199, is an orally bioavailable, selective small molecule inhibitor of the anti-apoptotic protein Bcl-2, with potential antineoplastic activity. Venetoclax mimics BH3-only proteins, the native ligands of Bcl-2 and apoptosis activators, by binding to the hydrophobic groove of Bcl-2 proteins thereby repressing Bcl-2 activity and restoring apoptotic processes in tumor cells. Bcl-2 protein is overexpressed in some cancers and plays an important role in the regulation of apoptosis; its expression is associated with increased drug resistance and tumor cell survival. Compared to the Bcl-2 inhibitor navitoclax, this agent does not inhibit bcl-XL and does not cause bcl-XL-mediated thrombocytopenia....

AbbVie (NYSE: ABBV), a global biopharmaceutical company,  announced that a Phase 2 trial of its investigational medicine venetoclax met its primary endpoint of achieving overall response rates in patients with relapsed/refractory or previously untreated chronic lymphocytic leukemia (CLL) with 17p deletion, according to an independent review analysis. The open-label study evaluated the efficacy and safety of venetoclax, an inhibitor of the B-cell lymphoma-2 (BCL-2) protein that is being developed in partnership with Genentech and Roche.

Data from this study will be presented at an upcoming medical conference and will serve as the pivotal registration data for applications to the FDA, EMA and other health authorities. The safety profile was similar to previous studies and no unexpected safety signals were reported for venetoclax.

AbbVie's venetoclax Phase 2 trial meets primary endpoint in patients with relapsed/refractory CLL with 17P deletion

Vascular side effects prevent first-line ponatinib use in chronic phase CML

 

In continuation of my update on Ponatinib 

Ponatinib is highly active when given to patients within 6 months of developing chronic phase chronic myeloid leukaemia (CML), phase II results show, but its toxicity profile is unacceptable for first-line treatment.

The investigators, from the University of Texas MD Anderson Cancer Center in Houston, USA, report “deep and early responses” to the third-generation tyrosine kinase inhibitor (TKI) in The Lancet Haematology.

“However, due to the risk of vascular thrombotic events and the availability of alternative options for these patients, other drugs should be considered first in the frontline setting”, recommend Jorge Cortes and co-authors.

At 6 months, a complete cytogenetic response (CCyR) was achieved by 94% of 46 assessed patients and a major molecular response (MMR, BCR–ABL1 ≤0.1%) by 83%, with undetectable levels of BCR–ABL1 in 22% of assessed patients and a level of 1% or below in 96%.

The median times to a complete haematological response, CCyR and MMR were 0.6, 2.89 and 2.90 months, respectively, and there was 100% overall and transformation-free survival after 2 years.

But the initial starting dose of 45 mg/day in 43 patients was reduced to 30 mg/day or 15 mg/day for 18 patients after tolerability issues, while six of eight patients started on 30 mg/day had the dose reduced to 15 mg/day. At least one treatment interruption was required by 85% of patients, while 88% had their dose reduced due to adverse events (66%) or US Food and Drug Administration (FDA) advice (24%).

All of these patients finally discontinued ponatinib therapy and switched to an alternative TKI following adverse events or FDA concerns about an increased risk of thromboembolism.

In all, 49% of patients experienced cardiac or vascular events and 22% had more than one such episode. These included worsening or new-onset of hypertension, one case each of acute coronary syndrome and myocardial infarction, and three cases of vaso-occlusive disease. Two patients experienced cerebrovascular events, and one patient developed pulmonary hypertension within a month of discontinuing ponatinib.

Vascular side effects prevent first-line ponatinib use in chronic phase CML

MedDay announces additional positive results from MD1003 Phase III trial in patients with progressive MS

MedDay, a biotechnology company focused on the treatment of nervous system disorders, reports additional positive data from its pivotal Phase III clinical trial, MS-SPI, with MD1003, a highly-concentrated pharmaceutical grade biotin, in patients with Progressive Multiple Sclerosis. The data, to be announced on Saturday 20th June at The 1st Congress of the European Academy of Neurology (EAN), shows an improvement of the Clinical Global Impression of change observed after 12 months of treatment with MD1003 and confirms the positive results presented at the American Academy of Neurology in April 2015.

The Clinical Global Impression of change is a 7 point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention and rated as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. During the MS-SPI trial, the Clinical Global Impression of change has been assessed by the clinician (clinician global impression, CGI) as well as by the patient (subject global impression, SGI) after 12 months of treatment. Mean CGI and SGI scores assessed at month 12 were statistically significantly better in the intervention group compared with the placebo group (p<0.0001 and p=0.0094, respectively).

These important results confirm the previously reported data of MS-SPI where the primary endpoint was defined as the proportion of patients who improved either on EDSS or on timed 25-foot walk (TW25) at M9, with a confirmation of the improvement at 12 months (M12) was met (p=0.0051). The mean change of EDSS between M0 and M12 decreased in the MD1003 group (-0.03) compared to progression in the placebo group (+0.13, p=0.014). In the MD1003 arm, only 4% of patients treated with MD1003 exhibited EDSS progression at M9 confirmed at M12 vs 13% in the placebo group (p=0.07), which equates to a 67% decreased risk of progression in the active arm within the studied period.

MedDay announces additional positive results from MD1003 Phase III trial in patients with progressive MS

Scientists identify new agent to combat tuberculosis

(Griselimycin)

Above pic: The protein forms a homodimeric ring (shown as blue cartoon & surface representation). Each polypetide chain binds one molecule of griselimycin (red). The optimized compound cyclohexylgriselimycin contains an additional cyclohexane moiety (yellow, shown only for the ligand in the foreground).

According to figures of the World Health Organization, some 8.7 million people contracted tuberculosis in 2012 and this disease is fatal for approximately 1.3 million people throughout the world each year. One of the main problems is that the tuberculosis pathogens have become resistant to the antibiotics used to fight them. Scientists from the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) in Saarbrücken, the Helmholtz Centre for Infection Research (HZI) in Braunschweig and the German Center for Infection Research (DZIF) joined forces with scientists from Sanofi, a global health care company, and identified a new agent, which might potentially remedy these problems. The scientists just described this agent and its unique mechanism of action in the highly renowned scientific journal Science.

Mycobacterium tuberculosis is the main cause of tuberculosis. The treatment for drug-susceptible tuberculosis consists of the daily administration of multiple drugs for a minimum of six months. Lack of adherence to this regimen can result in treatment failure and the emergence of drug resistance. "Complexity and duration of the treatment are true issues and the main reasons for the development of resistant pathogens," says Prof Rolf Müller, who is the Executive Director and head of the Microbial Natural Substances department of the HIPS, an institution jointly sponsored by the HZI and Saarland University.

Consequently, there is an urgent need for new medications and therapeutic approaches to both fight the resistant pathogens, as well as to shorten the duration for the treatment of drug-susceptible organisms. Based on earlier reports, Müller, in collaboration with Prof Jacques Grosset from the Johns Hopkins University School of Medicine in Baltimore, and his colleagues from the HZI and Sanofi scientists, initially focused on the natural substance called griselimycin. The potential of this natural substance, was discovered in the 1960s. However, due to the success of other tuberculosis medications and its low efficacy in an infection model, the substance was not developed any further at the time.

"We resumed the work on this agent and optimised it such that it shows excellent activity in the infection model - even against multi-resistant tuberculosis pathogens," says Müller. In the course of their work, the scientists discovered that cyclohexylgriselimycin, a variant of griselimycin, is particularly effective against Mycobacterium tuberculosis, both in cells and in the animal model. Importantly, cyclohexylgriselimycin was effective when administered orally, which is key in tuberculosis treatment, non-orally available drugs are extremely burdensome to administer daily during the many months of treatment. Moreover, combining this substance with current TB antibiotics increases the efficacy compared to the antibiotic cocktail that is usually administered.

Scientists identify new agent to combat tuberculosis