Archive for the ‘Therapeutic Classification’ Category

Irinotecan and Temozolomide Shows Promise in Breast Cancer Study

Friday, October 24th, 2014

Irinotecan and Temozolomide Shows Promise in Breast Cancer StudyEwing sarcoma tumors disappeared and did not return in more than 70% of mice treated with combination therapy that included Irinotecan and Temozolomide, which are experimental agents developed to fight breast cancer, reported St. Jude Children’s Research Hospital scientists. The study will appear in the November 6 edition of the scientific journal Cell Reports. The treatment paired two chemotherapy drugs currently used to treat Ewing sarcoma (EWS) with experimental drugs called poly-ADP ribose polymerase (PARP) inhibitors that interfere with DNA repair. PARP inhibitors are currently in clinical trials for the treatment of certain breast and ovarian cancers as well as other solid tumors. EWS is a cancer of the bone and soft tissue that strikes primarily adolescents and young adults.

A clinical trial using the three-drug combination therapy detailed in this research is expected to open later this year for adolescents and young adults with EWS whose tumors have not disappeared with standard therapy or have returned after treatment. The trial is a collaboration of researchers at St. Jude and the Dana-Farber/Harvard Cancer Center in Boston. The therapy will pair the PARP inhibitor Olaparib with the chemotherapy drugs Irinotecan and Temozolomide. The study is one of two clinical trials St. Jude plans to open soon combining Irinotecan and Temozolomide with PARP inhibitors for the treatment for EWS. The tumor is diagnosed in about 250 U.S. residents each year, making it the second most common bone tumor in children and adolescents. Long-term survival for EWS patients whose disease has not spread remains stalled at about 75 to 80 percent, and the outcome for patients with metastatic disease is dismal. “During the past 20 years there has been no significant improvement in the cure rate for Ewing sarcoma, and survival is just 15 to 20 percent for patients whose disease has spread or comes back after treatment,” said co-corresponding author Michael Dyer, Ph.D., a Howard Hughes Medical Institute (HHMI) investigator and a member of the St. Jude Department of Developmental Neurobiology. The other corresponding author is Anang Shelat, Ph.D., an assistant member of the St. Jude Department of Chemical Biology and Therapeutics.

This study builds on earlier research from other investigators who reported that EWS cells growing in the laboratory were sensitive to the PARP inhibitor Olaparib. A clinical trial of Olaparib for treatment of adults with EWS that had spread or returned opened a short time later. The latest report includes the St. Jude discovery that EWS cells have a defect in DNA damage repair. DNA is the molecule contained in nearly every cell that carries the instructions needed to assemble and sustain life.

Working with EWS cells grown in the laboratory and mice, investigators showed the EWS defect could be exploited to help patients by combining DNA-damaging chemotherapy with a PARP inhibitor. PARP inhibitors work by interfering with activity of an important DNA-repair enzyme. St. Jude researchers conducted a series of mouse experiments designed to mirror the human phase I, II and III studies that gauge the safety and effectiveness of experimental treatment in humans. The research showed that PARP inhibitors work synergistically with Irinotecan and Temozolomide to kill EWS. The Phase III study included 274 mice with EWS treated in a double-blind, placebo controlled, randomized study. The study included 15 different treatment groups using different combinations and doses of Irinotecan, Temozolomide and three PARP inhibitors currently in development for pediatric cancer treatment. EWS disappeared and had not returned in more than four months in 71 percent of mice treated with Irinotecan, Temozolomide and the PARP inhibitor Olaparib. The results were even better when Irinotecan and Temozolomide were combined with the PARP inhibitor talazoparib. The combination led to a durable, complete remission in 88 percent of the 16 mice treated. “Our preclinical results suggest Ewing sarcoma is particularly sensitive to this combination therapy, a possible indication that the tumor’s DNA repair defect provides us with a much needed advantage to knock out tumor cells,” Shelat said. “There is some evidence that this type of defect is present in other pediatric tumors, and we are actively investigating drug sensitivity in those cancers.”

Researchers used the low-dose, protracted Irinotecan treatment schedule pioneered at St. Jude to reduce Irinotecan toxicity. Adult cancer patients receive fewer, but higher doses of Irinotecan. The adult treatment regimen led to higher toxicity in mice. “The only way to move forward was using the irinotecan approach proven in earlier St. Jude solid tumor clinical research,” Dyer said. One of the planned St. Jude-led clinical trials will combine talazoparib and Irinotecan for the treatment of patients age 1 and older. The other will involve triple drug therapy for treatment of patients age 16 and older.

LGM Pharma is a supplier / distributor of the APIs Irinotecan CAS# 100286-90-6 and Temozolomide CAS# 85622-93-1 for research and development purposes. Clients can be assured of quality API products and continuous support throughout the R&D process.

Products currently covered by valid US Patents are offered for R&D use in accordance with 35 USC 271(e)+A13(1). Any patent infringement and resulting liability is solely at buyer risk.

Early EU Approval for Ibrutinib

Tuesday, October 21st, 2014

IbrutinibThe early EU approval for Ibrutinib was granted by the European Commission (EC), for Ibrutinib to be sold in the 28 European Union (EU) member states.

Ibrutinib is a first-in-class, oral, once-daily, non-chemotherapy treatment option, and will be used to treat adult patients with relapsed or refractory mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL).

This likely new cancer blockbuster is marketed as the trade name Imbruvica, and is being jointly developed and commercialized in the U.S. by Pharmacyclics and Janssen Biotech, Inc. (Janssen). Janssen affiliates will sell Imbruvica in EMEA (Europe, Middle East, Africa), as well as the rest of the world, outside the U.S. In addition to EU markets, a worldwide regulatory filing program for ibrutinib is currently underway.

In the US, Imbruvica obtained approval to treat patients with MCL and CLL who have received at least one prior therapy, and for the treatment of CLL patients with deletion of the short arm of chromosome 17 (del 17p), including treatment-naive and previously treated del 17p CLL patients.

The EC approval was based on data from the Phase 2 study (PCYC-1104) in MCL, the Phase 3 RESONATE™ study (PCYC-1112-CA) in CLL and small lymphocytic lymphoma (SLL) and the Phase Ib/II study (PCYC-1102) in CLL/SLL. This approval is based on the Imbruvica Marketing Authorization Application (MAA) submitted to the European Medicines Agency (EMA) last year.

In 2013 the NDA for Ibrutinib was placed on a priority basis by the FDA after a Phase 2 multicenter study of Ibrutinib was presented, and it identified a staggering 70% response rate from MCL patients with 68% of patients demonstrating an overall response rate after roughly nine months.

In June 2014, study results revealed Ibrutinib elicited a significant improvement for patients with either CLL or SLL in both overall survival and progression free survival in a study comparing it with Ofatumumab.

LGM Pharma is a provider of the APIs Ibrutinib, CAS # 936563-96-1 for research and development purposes. Clients can be assured of quality API products and continuous support throughout the R&D process.

Products currently covered by valid US Patents are offered for R&D use in accordance with 35 USC 271(e)+A13(1). Any patent infringement and resulting liability is solely at buyer risk.

Tavaborole Approved as Antifungal Toenail Treatment

Monday, October 20th, 2014

Tavaborole CAS 174671-46-6 Onychomycosis TreatmentAnacor Pharmaceuticals, Inc. ANAC, announced on Jul 08, 2014 that the FDA has approved the New Drug Application for Tavaborole, which is marketed as KERYDIN™ topical solution, 5%. Tavaborole was designed to be convenient for patients to use and it’s the first oxaborole antifungal approved for the topical treatment of onychomycosis of the toenails.

Onychomycosis is a progressive, recurring fungal infection of the nail and nail bed that affects approximately 35 million people in the United States, according to Podiatry Today.

Tavaborole is a broad-spectrum oxaborole antifungal agent with low molecular weight, permitting optimal nail plate penetration. Tavaborole is a clear, colorless, alcohol-based solution applied with a dropper to the infected toenail once daily for 48 weeks. Debridement of the nail is not required during the treatment period. Due to its topical application, KERYDIN has low systemic absorption and has not demonstrated systemic side effects.

Studies have demonstrated the superior nail-penetrating properties of tavaborole compared to existing topical antifungal medications approved for the treatment of onychomycosis.

Onychomycosis is one of the most common diseases diagnosed causing approximately one-half of all nail disorders, and it’s prevalence has been steadily increasing. It is difficult to treat, partly due to the subungual location and the inability of both oral and topical antifungals to reach the site of infection. Historically, a large number of patients with onychomycosis would choose not to treat their infection. With the approval of Tavaborole, physicians can now offer patients a safe, effective and easy-to-use topical treatment for their onychomycosis of the toenail.

LGM Pharma can assist clients as a supplier/distributor of Tavaborole CAS No: 174671-46-6, for research and development purposes. Clients can be assured of quality API products and continuous support throughout the R&D process.

Products currently covered by valid US Patents are offered for R&D use in accordance with 35 USC 271(e) +A13(1). Any patent infringement and resulting liability is solely at buyer risk.

Idelalisib EU Approval Granted For Treating CLL and FL Patients

Wednesday, September 24th, 2014

Idelalisib CAS 870281-82-6Gilead Sciences has been granted marketing authorization by the European Commission for its Idelalisib 150mg tablets (to be marketed as Zydelig) to treat the two incurable blood cancers Chronic Lymphocytic Leukemia (CLL) and Follicular Lymphoma (FL). This formidable first-in-class oral inhibitor of phosphoinositide 3-kinase (PI3K) delta, plays a key role in the activation, proliferation and viability of B cells, a critical component of the immune system.

The EU indications are similar, but not identical, to those in the U.S., where Idelalisib was approved in July 2014. For the treatment of CLL, the Idelalisib EU approval covers the use of Idelalisib combined with Rituximab for patients who have received at least one prior therapy (same as the US indication).

chronic lymphocytic leukemia (CLL)This Idelalisib EU approval was based mainly on a trial in 220 patients that was stopped early after it showed a significantly longer progression-free survival in patients receiving Idelalisib plus Rituximab. The results were published earlier this year in the New England Journal of Medicine. Researchers concluded that the addition of Idelalisib to Rituximab “provided effective durable disease control and improved overall survival for patients with relapsed CLL who were not suitable for cytotoxic chemotherapy, including high-risk patients.” Researchers also mentioned that treatment for CLL can be worse than the disease, leading to a great deal of side effects and death.

Idelalisib will be administered along with Rituximab for patients fighting refractory CLL. While there is a slight risk of serious toxicities, the majority of patients had common adverse reactions that were not deemed severe, and included pyrexia, abdominal pain, diarrhea, nausea and a mild rash. These adverse effects were seen in patients who were administered Idelalisib both with and without the addition of Rituximab.

Idelalisib is also EU approved to treat Follicular Lymphoma (FL) as monotherapy in patients who are refractory to two prior lines of treatment. This approval is supported by positive data from a phase 2 study of Idelalisib monotherapy in 125 patients.

The researchers concluded that Idelalisib “appears to provide effective oral monotherapy in patients with previously treated indolent non–Hodgkin’s lymphoma,” and these data were described as “eyebrow raising” when they were first presented at the 2103 American Society of Hematology meeting.

The advent of Idelalisib offers patients with these hard to treat forms of blood cancers better options for treatment and hope for tangible progression free survival. Idelalisib is also easy to administer as oral tablets which are typically taken twice daily, either with or without food. There are over 200,000 patients in the United States who suffer from relapsed follicular B-cell non-Hodgkin lymphoma, relapsed chronic lymphocytic leukemia or small lymphocytic lymphoma. This patient population is clearly in need of innovative and effective treatments.

LGM Pharma can assist clients as a supplier/distributor of Idelalisib, CAS # 870281-82-6, for research and development purposes. Clients can be assured of quality API products and continuous support throughout the R&D process.

 

Products currently covered by valid US Patents are offered for R&D use in accordance with 35 USC 271(e) +A13(1). Any patent infringement and resulting liability is solely at buyer risk.

FDA Approves Contrave – A Naltrexone Hydrochloride and Bupropion Hydrochloride Drug Combo

Friday, September 12th, 2014

Bupropion NaltrexoneOn September 10, 2014, The U.S. Food and Drug Administration (US FDA) approved Contrave (naltrexone hydrochloride and bupropion hydrochloride extended-release tablets) for anti-obesity treatments in combination with a reduced-calorie diet and exercise. Contrave is distributed by Takeda Pharmaceuticals America Inc. of Deerfield, Illinois for Orexigen Therapeutics, Inc. of La Jolla, California.

The FDA approved the naltrexone hydrochloride and bupropion hydrochloride drug combo for use by people with a body mass index of 30 or higher. It is also approved for use by people with a BMI of 27 or higher who also have a weight-related medical condition such as high blood pressure (hypertension), diabetes, or high cholesterol (dyslipidemia).

The naltrexone and bupropion drug combo are already approved for alcohol and narcotic dependence. In addition, naltrexone has already been approved for treating alcohol and narcotic dependence, and bupropion has already been approved as an antidepressant to help people quit smoking.

obesity in america In addition to Contrave, the FDA has approved 2 other drugs for anti-obesity treatments, including Qsymia from Vivus Inc. and Belviq from Arena Pharmaceuticals Inc. Sales of the drugs, once considered potential billion-dollar sellers, have been below expectations because of limited insurance coverage and high costs for patients.

In experiments, non-diabetic patients lost 4.1 percent more weight than patients who took a fake pill.

The drug will have a boxed warning about the risk of suicidal thoughts associated with antidepressants like Bupropion. Additional risks include the possibility of seizures, as well as increased blood pressure and heart rates.

The heart effects created a long road to approval for Contrave. The FDA refused to approve the drug in 2011, citing cardiovascular risks. Orexigen resubmitted its application to regulators in December, saying that the drug fared well in an early analysis of a study designed to rule out excessive cardiovascular risk.

Contrave will be distributed in the U.S. by Japanese drugmaker Takeda Pharmaceuticals, which will pay Orexigen royalties on sales. Orexigen and Takeda plan to start selling the drug in the fall of 2014.

 

Products currently covered by valid US Patents are offered for R&D use in accordance with 35 USC 271(e) +A13(1). Any patent infringement and resulting liability is solely at buyer risk.