Mirati: Initial Data In Renal Cell Carcinoma Sitravatinib Combo Trial

Mirati Therapeutics, Inc. (NASDAQ: MRTX), a clinical stage targeted oncology company, today announced the presentation of initial data from an ongoing investigator sponsored Phase 1/2 clinical trial of sitravatinib in combination with nivolumab (OPDIVO^®) in patients with advanced clear cell renal cell cancer (aCCRCC) who have documented progression on a prior VEGF-targeted therapy. The data were presented today in an oral abstract presentation by Pavlos Msaouel, M.D., Ph.D., Assistant Professor, Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, at the 2020 ASCO Genitourinary Cancers Symposium in San Francisco, CA.

“The initial efficacy data from the Phase 1/2 clinical trial presented today demonstrates encouraging durable responses, when compared with progression-free survival rates expected with nivolumab alone in aCCRCC patients that progressed on prior VEGF-targeted therapy,” said Charles M. Baum, M.D., Ph.D., President and Chief Executive Officer of Mirati. “These data indicate the potential range of extended clinical benefit beyond checkpoint refractory non-small cell lung cancer and metastatic urothelial cancer.”

As of the data cut-off date of January 1, 2020, 38 out of 40 patients enrolled were evaluable for response at greater than 12 weeks on therapy:

• 15/38 (39%) patients achieved a confirmed partial response (PR) including one PR that has improved to an unconfirmed complete response (CR)
• 35/38 (92%) patients achieved clinical benefit (combination of stable disease plus PR plus CR)
• Initial median progression-free survival (PFS) was 10.3 months
• Median overall survival (OS) has not yet been reached (median follow-up was 17.7 months) with 30/38 patients (79%) still on study as of the data cut-off date.

The combination has been well-tolerated with manageable adverse events.

https://www.biospace.com/article/releases/mirati-therapeutics-announces-initial-data-in-renal-cell-carcinoma-from-ongoing-investigator-sponsored-clinical-trial-of-sitravatinib-in-combination-with-nivolumab-at-the-2020-asco-genitourinary-cancers-syposium/

FDA approves Glaxo Voltaren Arthritis Pain for over-the-counter use

GlaxoSmithKline (LSE/NYSE: GSK) today announced that the U.S. Food and Drug Administration (FDA) has approved Voltaren Arthritis Pain (diclofenac sodium topical gel, 1% (NSAID)- arthritis pain reliever) as an over-the-counter (OTC) product for the temporary relief of arthritis pain in the hand, wrist, elbow, foot, ankle or knee in adults (18 years and older).  With the FDA’s approval, Voltaren Arthritis Pain becomes the first and only prescription strength, nonsteroidal anti-inflammatory (NSAID) topical gel for arthritis pain available OTC in the United States.

Voltaren Gel, which GSKCH owns the rights to, is currently only available with a prescription in the US. Today’s OTC approval of Voltaren Arthritis Pain will provide the nearly 30 million Americans with osteoarthritisⁱ over-the-counter access to this topical treatment option.

Franck Riot, Head of R&D, GSK Consumer Healthcare said: “For the millions of people around the world living with arthritis, joint pain and stiffness are daily realities. At GSK, we are committed to improving the quality of life of these people and today’s approval is progress towards this, providing consumers in the US with increased access to an effective, proven arthritis pain relief option. Voltaren is currently the number 1 OTC topical pain relief brand globally, and we look forward to expanding its availability in the US.”

https://www.biospace.com/article/releases/fda-approves-gsk-s-voltaren-arthritis-pain-for-over-the-counter-use-in-the-united-states/

Bristol: Positive Long-Term Data for RCC Patients Treated with Opdivo and Yervoy

Long-term data boosts the efficacy of Bristol-Myers Squibb’s checkpoint inhibitor, Opdivo, as a treatment for renal cell carcinoma (RCC). Over the weekend, the company released follow-up results from two studies that support the survival benefits of patients treated with the medication.

At the American Society of Clinical Oncology 2020 Genitourinary Cancers Symposium in San Francisco, BMS presented long-term data from the CheckMate-214 and CheckMate-025 studies in advanced or metastatic renal cell carcinoma that showed the “durable, long-term survival benefits for Opdivo (nivolumab) with or without Yervoy (ipilimumab) across first and second-line treatment settings.”

In the CheckMate-025 study, BMS released five-year follow-up results that showed treatment with Opdivo continues to deliver “superior overall survival (OS) and objective response rates (ORR)” in patients with previously treated advanced or metastatic renal cell carcinoma compared to those treated with Novartis’ Afnitor (everolimus). The five-year data showed that patients treated with Opdivo continue to demonstrate OS benefit with 26% of patients alive compared to 18% of patients treated with everolimus, the company said during its presentation. Additionally, the percentage of patients experiencing an objective response was 23% for Opdivo versus 4% for everolimus.

When it came to the median duration of response (mDOR), the CheckMate-025 data showed that patients treated with Opdivo maintained their response longer than those on the Novartis medication, 18.2 months vs. 14 months, respectively.

The overall safety profile was consistent with that observed in previously reported analyses from CheckMate -025 in patients with RCC. No new safety signals or drug-related deaths occurred with extended follow-up, BMS said.

Brian Lamon, development lead of genitourinary cancers at BMS, said the updated results from CheckMate-025 support the reason Opdivo as a standalone treatment “became a standard of care for previously treated RCC patients worldwide and offer additional evidence that treatment with Opdivo has the potential to help patients live longer.” He added that the study represents exciting progress in the company’s mission to improve survival outcomes for all patients.

Renal cell carcinoma is the most common type of kidney cancer in adults, accounting for more than 140,000 deaths worldwide each year. Globally, the five-year survival rate for those diagnosed with metastatic, or advanced, kidney cancer is 12.1%.

In the CheckMate-214 follow-up, BMS said four-year data showed that those patients treated with a combination of Opdivo and Yervoy continued to yield superior overall survival (OS), objective response rates (ORR), duration of response and complete response rates compared to Pfizer’s Sutent (sunitinib) in patients with previously untreated advanced or metastatic RCC. The long-term data from CheckMate-214 showed that more than 50% of patients treated with Opdivo plus Yervoy were alive at 42 months compared to 39% of patients treated with sunitinib. The OS rate was 52% for patients treated with Opdivo and Yervoy compared to 39% for patients treated with sunitinib alone. The four-year data reinforces the depth and durability of response previously observed with the combination in the first-line patient population, BMS said.

The company said the complete response rates for the combination treatment were maintained and ongoing in more than 80% of the patients. Also, BMS said the four-year results from CheckMate-214 represent the longest follow-up “with any immuno-oncology-based therapy in this setting.”

The safety profile for the combination therapy remained consistent with previous studies.

Lamon said the findings from CheckMate-214 demonstrate the “complementary nature of dual immuno-therapy and reinforce the depth and durability of response the combination of Opdivo plus Yervoy can deliver for patients.”

https://www.biospace.com/article/long-term-data-shows-success-of-treating-rcc-with-opdivo-and-yervoy-bms-says/

PharmaMar, Jazz Eye Potential Approval of Lung Cancer Drug Lurbinectedin

Jazz Pharmaceuticals and Spain-based PharmaMar anticipate potential approval of a small cell lung cancer treatment by the end of summer. The U.S. Food and Drug Administration accepted the companies’ New Drug Application for lurbinectedin under Priority Review.

This morning the companies said the FDA gave a PDUFA target action date of Aug. 16 for the treatment of small cell lung cancer (SCLC) who have progressed after prior platinum-containing therapy. PharmaMar and Jazz submitted their NDA in December based on data from the Phase II monotherapy basket trial, which evaluated lurbinectedin for the treatment of relapsed SCLC. The trial met its primary endpoint of the objective response rate (ORR) and the results were presented at the 55th Annual Meeting of the American Society of Clinical Oncology (ASCO) in June 2019. The Phase II data showed that ORR was 35.2% in the total trial population and 45% in patients with sensitive disease, which was classified as those patients who suffered a relapse of the disease in a period greater than or equal to 90 days. The data also showed that ORR was 22.2% in patients with resistant disease, meaning patients who have suffered a relapse of the disease in a period of less than 90 days.

Following the Phase II data, PharmaMar announced in August 2019 that it would submit its NDA under accelerated approval of lurbinectedin as a monotherapy second-line treatment for SCLC. The accelerated approval program allows the submission of an NDA based on a Phase II study for serious conditions that satisfy an unmet medical need. SCLC is an aggressive form of the disease usually diagnosed in an advanced or metastatic state, which limits the role of traditional approaches. The treatment landscape has not changed substantially in more than two decades since the last new chemical entity, topotecan, was approved, PharmaMar said. SCLC represents between 10% and 15% of all lung cancers. There are approximately 30,000 new cases of SCLC diagnosed in the U.S. each year. Lurbinectedin was granted orphan drug designation for SCLC by FDA in August 2018.

Lurbinectedin (PM1183) is a selective inhibitor of the oncogenic transcription programs on which many tumors are dependent. Lurbinectedin inhibits oncogenic transcription in tumor-associated macrophages, downregulating the production of cytokines that are essential for the growth of the tumor, according to company data.

José María Fernández Sousa-Faro, president of PharmaMar, said in the United States, “lurbinectedin has the potential to become a therapeutic alternative for patients with relapsed small cell lung cancer, who have limited treatment options.”

In December, PharmaMar and Jazz entered into an exclusive license agreement for lurbinectedin in the United States. Ireland-based Jazz paid PharmaMar $200 million upfront, with the promise of nearly $800 million more in potential regulatory and commercial milestone payments.

As the company awaits the FDA’s decision of lurbinectedin as a monotherapy, last month it began to explore the drug in concert with immunotherapy drugs. The company launched a Phase I/II trial in combination with Roche’s Tecentriq (atezolizumab) as a potential treatment of patients with advanced SCLC.

https://www.biospace.com/article/pharmamar-and-jazz-eye-august-for-potential-approval-of-sclc-drug-lurbinectedin/

New Molecule Has the Potential of Stopping or Slowing Parkinson’s

Parkinson’s disease affects the brain’s nerve cells that produce dopamine. The symptoms include muscle rigidity, tremors, and changes in speech and gait. Researchers at the University of Helsinki have identified a molecule called BT13 that potentially can increase levels of dopamine.

By the time someone is diagnosed with Parkinson’s disease, they have typically lost 70 to 80% of their dopamine-producing cells, which assist in coordinating movement. Treatments today mask the symptoms, but there is nothing on the market that slows down the disease progression or prevents more brain cells from dying. As the levels of dopamine drop, symptoms get worse.

Their research builds on work on glial cell line-derived neurotrophic factor (GDNF), which is another molecule that targets the same receptors in the brain. In a large clinical trial funded by Parkinson’s UK, the molecule showed promise in restoring damaged cells in Parkinson’s, although the results were not completely clear.

Also, because GDNF is a very large molecule, it requires complex surgery to deliver it to the brain. BT13, on the other hand, is a small molecule, making it easier to administer.

“This molecule holds great promise. People with Parkinson’s desperately need a new treatment that can stop the condition in its tracks, instead of just masking the symptoms,” said David Dexter, deputy director of Research at Parkinson’s UK. “One of the biggest challenges for Parkinson’s research is how to get drugs past the blood-brain barrier, so the exciting discovery of BT13 has opened up a new avenue for research to explore.”

The research was published in the journal Movement Disorders.

RET is a receptor tyrosine kinase, which is a GDNF receptor. The authors write, “We characterized the ability of BT13 to activate RET in immortalized cells, to support the survival of cultured dopamine neurons, to protect cultured dopamine neurons against neurotoxin-induced cell death, to activate intracellular signaling pathways both in vitro and in vivo, and to regulate dopamine release in the mouse striatum as well as BT13’s distribution in the brain.”

At this point, BT13 showed promise worth further development.

“More research is needed to turn BT13 into a treatment to be tested in clinical trials, to see if it really could transform the lives of people living with Parkinson’s,” said Dexter.

Yulia Sidorova, the lead researcher of the study, said, “We are constantly working on improving the effectiveness of BT13. We are now testing a series of similar BT13 compounds, which were predicted by a computer program to have even better characteristics. Our ultimate goal is to progress these compounds to clinical trials in a few coming years.”

According to Parkinson’s News Today, seven to 10 million people worldwide have Parkinson’s disease. In people in their forties, it occurs in about 41 out 100,000 people, and more than 1,900 per 100,000 in people 80 and older. About 4% of people diagnosed are younger than 50. Men are 1.5 times more likely to have Parkinson’s than women.

In the U.S., the disease is thought to afflict 1 million people, with about 60,000 people newly diagnosed each year.

https://www.biospace.com/article/new-molecule-has-the-potential-of-stopping-or-slowing-parkinson-s/

FDA Action Alert: Merck, Baudax Bio, Alder and Esperion

The U.S. Food and Drug Administration (FDA) has a busy week planned for drug review. Here’s a look at this week’s schedule.

6 Supplemental BLAs for Merck’s Keytruda

Merck & Co. has a target action date of February 18, 2020 for six supplemental Biologics License Applications (sBLAs) to update the dosing frequency of its blockbuster checkpoint inhibitor Keytruda (pembrolizumab), to include every-six-weeks (Q6tW) dosing. It is seeking approval of a 400 mg Q6W dose infused over 30 minutes for indications in melanoma, classical Hodgkin lymphoma, primary mediastinal large B-cell lymphoma, gastric cancer, hepatocellular carcinoma and Merkel cell carcinoma.

“If approved, the six-week dosing schedule will provide physicians and patients with greater flexibility in their treatment plans across a variety of cancer types, including melanoma where Keytruda is indicated in both the adjuvant and metastatic settings,” said Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories, in July 2019.

Baudax Bio’s IV Meloxicam for Moderate to Severe Pain

Baudax Bio, headquartered in Malvern, Pennsylvania, has a target action date of February 20 for its New Drug Application (NDA) for IV meloxicam for the management of moderate to severe pain. The drug had received a complete response letter (CRL) in 2019 and after appealing, was accepted for review.

IV meloxicam is a non-opioid pain medication to treat moderate to severe pain. The submission was based on the results of three Phase III clinical trials, two efficacy studies and one safety study, four Phase II trials, and other studies. Maloxicam is a long-acting, preferential COX-2 inhibitor that shows analgesic, anti-inflammatory and antipyretic activities. The IV dosing was developed using the NanoCrystal platform.

In a January 22, 2020 statement, Gerri Henwood, president and chief executive officer of Baudax said, “We are pleased by the FDA’s acceptance of our latest response package, which we believe addresses their concerns and which includes proposed labeling for IV meloxicam for the management of moderate to severe pain, alone or in combination with other analgesics. We will be working closely with the FDA as they complete their review of the IV meloxicam NDA and work toward the PDUFA goal date.”

Baudax Bio launched in November 2019 as an independent, publicly-traded pharma company. It was launched with $19 million from Recro Pharma, its former parent company, and holds the rights to IV meloxicam, two neuromuscular blocking agents and a reversal agent, and dexmedetomidine dosage forms.

Alder BioPharma’s Eptinezumab for Migraine

Alder BioPharmaceuticals, headquartered in Bothell, Washington, has a target action date of February 21 for its BLA of eptinezumab for episodic and chronic migraine. The drug targets the calcitonin gene-related peptide (CGRP). The BLA is supported by positive data from the company’s PROMISE 1 and PROMISE 2 Phase III clinical trials and other data. If approved by the FDA, it will be the first IV CGRP therapy for migraine prevention.

On September 16, 2019, Denmark-based H. Lundbeck A/S announced the acquisition of Alder with an upfront payment of $18 per share and one non-tradeable Contingent Value Right (CVR) for another $2 per share if eptinezumab is approved by the European Medicines Agency (EMA). This is valued at up to $1.95 billion. The acquisition was completed on October 22, 2019.

Esperion’s Bempedoic Acid and Combo Tablet for High Cholesterol

Esperion, based in Ann Arbor, Michigan, has a target action date of February 21 and February 26 for its bempedoic acid and bempedoic acid/ezetimibe for increased low-density lipoprotein cholesterol (LDL-C), respectively.

On November 17, 2019, Esperion announced pooled analyses from four Phase III trials of bempedoic acid, which were presented at the American Heart Association (AHA) Scientific Sessions in Philadelphia. The drugs are also being reviewed by the European Medicines Agency (EMA).

Bempedoic acid reduced HbA1c by 0.19% compared to placebo in patients with diabetes at 12 weeks. In a study of the drug in patients with high cholesterol when added to maximally tolerated statin therapy, decreased LDL-C by 18% compared to placebo, and in patients not on statin background therapy and considered statin intolerant, decreased LDL-C by25% compared to placebo. The Bempedoic acid/ezetimibe combination showed a 29% placebo corrected LDL-C lowering when used with maximally tolerated statins, a 44% LDL-C lowering with no background statin, and a 34% reduction in high sensitivity C-reactive protein (hsCRP).

https://www.biospace.com/article/fda-action-alert-merck-baudax-bio-alder-and-esperion/

Apple warns on revenue for March quarter

Thanks to the coronavirus, Apple (NASDAQ:AAPL) says it doesn’t expect to meet its March quarter revenue guidance.

The company notes both its supply from and demand within China has been affected.

Outside of China, says Apple, demand has been strong so far this quarter, and inline with expectations.

Source: Press Release

https://seekingalpha.com/news/3542507-apple-warns-on-revenue-for-march-quarter