FDA Grants Orphan Drug Status to Mocetinostat for DLBCL

Editor’s note: When a newly developed drug for a rare (“orphan”) disease seems particularly promising for patients, the U.S. Food and Drug Administration (FDA) may choose to grant it “orphan drug designation.” The designation removes certain barriers that might otherwise keep a drug company from being able to successfully develop and profit from the drug in the U.S. A new drug called mocetinostat has now been granted orphan drug designation for treating diffuse large B-cell lymphoma. The drug might be particularly effective for people whose tumors have mutations in the CREBBP and EP300 pathways; these mutations can be detected by molecular testing.

“The FDA granted orphan drug designation to mocetinostat for the treatment of patients with diffuse large B-cell lymphoma, its manufacturer announced today.

“Mocetinostat (Mirati Therapeutics), a histone deacetylase inhibitor developed as a single-agent treatment for patients with DLBCL and bladder cancer with specific genetic mutations in histone acetyl transferases, reverses aberrant acetylation from these mutations and is expected to halt tumor progression and reduce tumor burden.

“ ‘We have identified genetic alterations in histone acetylation pathways (CREBBP and EP300) in approximately one-third of DLBCL and bladder tumors. Nonclinical tumor models exhibiting these mutations are particularly responsive to mocetinostat,’ Charles Baum, MD, PhD, president and CEO of Mirati, said in a press release. ‘Among other benefits, orphan designation provides seven years of market exclusivity to target these genetically defined patients with unmet medical need in the event we achieve regulatory approval.’ ”

FDA Staff Questions Prostate Cancer Device Effectiveness

“A device used in Europe to treat prostate cancer with lower rates of erectile dysfunction raised concerns from U.S. regulators over data the company says shows it prevents the disease’s return.

“The device, called Ablatherm, is manufactured by EDAP TMS SA (EDAP), a French company. It’s an alternative to traditional surgical and radiation treatments, and uses a robotic arm to insert a high-intensity, focused ultrasound device that heats and kills cancer cells. The Food and Drug Administration said it will convene a panel of outside advisers on July 30 to discuss the risks and benefits of the device before the agency decides whether to approve it.

“While the company claims Ablatherm produces lower rates of side effects than traditional treatments, the FDA questioned whether the device’s effectiveness holds up, agency staff wrote in a report released today ahead of the advisory meeting.

“ ‘The clinical benefit of the subject device in the treatment of the low risk population is unclear,’ agency staff wrote in their report.

“The majority of men who get surgery or radiation for prostate cancer suffer from immediate or delayed erectile dysfunction. Of patients who used Ablatherm, 30 percent to 40 percent of men treated with the device in the 14 years it has been used in Europe had erection problems, less than traditional treatments, EDAP Chief Executive Officer Marc Oczachowski said in a telephone interview.”

FDA Expands Approved Use of Imbruvica for Chronic Lymphocytic Leukemia

Editor’s note: When a drug company creates a new cancer treatment, the treatment must be approved by the U.S. Food and Drug Administration (FDA) before doctors in the U.S. can prescribe it. An FDA approval for a new drug usually specifies the particular kinds of patients who are allowed to be treated. A drug called Imbruvica was recently FDA-approved for treating people with chronic lymphocytic leukemia (CLL) who have been previously but unsuccessfully treated with at least one other drug. Now, the FDA has also approved Imbruvica for people with CLL whose tumors have a genetic mutation called del 17p, as detected by molecular testing. People with this mutation are less likely to have success with standard CLL treatments, so Imbruvica could be a good alternative.

“The U.S. Food and Drug Administration today expanded the approved use of Imbruvica (ibrutinib) to treat patients with chronic lymphocytic leukemia (CLL) who carry a deletion in chromosome 17 (17p deletion), which is associated with poor responses to standard treatment for CLL. Imbruvica received a breakthrough therapy designation for this use.

“The FDA is also approving new labeling to reflect that Imbruvica’s clinical benefit in treating CLL has been verified. In February 2014, Imbruvica received accelerated approval to treat CLL based on its effect on overall response rate. New clinical trial results examining progression-free survival and overall survival have confirmed the drug’s clinical benefit.

“A type of non-Hodgkin lymphoma, CLL is a rare blood and bone marrow disease that usually gets worse slowly over time, causing a gradual increase in white blood cells called B lymphocytes, or B cells. The National Cancer Institute estimates that 15,720 Americans will be diagnosed and 4,600 will die from CLL in 2014. Imbruvica works by blocking the enzyme that allows cancer cells to grow and divide.”

FDA Grants Breakthrough Status to Immunotherapy Combination for Pancreatic Cancer

The gist: A new pancreatic cancer treatment combines two drugs, known as CRS-207 and GVAX Pancreas. This combo treatment boosts a patient’s own immune system to fight cancer. It has been tested in volunteer patients in clinical trials, and has shown promising results for people with metastatic pancreatic cancer. The U.S. Food and Drug Administration (FDA) has now granted breakthrough therapy designation for CRS-207 plus GVAX Pancreas, meaning that review and approval will be accelerated so that the drug can more quickly reach patients in the U.S., outside of clinical trials.

“The FDA today granted breakthrough therapy designation to the combination of two immunotherapies — CRS-207 and GVAX Pancreas — for the treatment of metastatic pancreatic cancer, according to Aduro BioTech, the combination treatment’s manufacturer.

“The combination of GVAX, an irradiated, granulocyte-macrophage colony–stimulating factor vaccine, and CRS-207, an immunotherapy vaccine containing live-attenuated Listeria monocytogenes bacteria, induces a potent innate and T-cell–mediated immune response.

“ ‘We are extremely pleased to receive Breakthrough Therapy Designation and the high degree of FDA collaboration toward advancement of our program that it confers,’ Stephen T. Isaacs, chairman, president and CEO of Aduro, said in a press release. ‘This designation underscores the potential of our combination immunotherapy approach to make a difference in the lives of patients with pancreatic cancer, which remains a very difficult cancer to treat. We are encouraged by our phase 2 results and look forward to completing enrollment in our phase 2b ECLIPSE trial by end of 2015.’ “

HCC Inhibitor Receives FDA Orphan Drug Designation

The gist: When a newly developed drug for a rare (“orphan”) disease seems particularly promising for patients, the U.S. Food and Drug Administration (FDA) may choose to grant it “orphan drug designation.” The designation removes certain barriers that might otherwise keep a drug company from being able to successfully develop and profit from the drug in the U.S. A new drug called ENDM-2076 has just received an orphan drug designation for the treatment of hepatocellular carcinoma (HCC).

“Casi Pharmaceuticals has received an orphan drug designation from the FDA for ENMD-2076 to treat hepatocellular carcinoma, according to a press release.

“With the status, Casi will be able to market ENMD-2076, an Aurora A/angiogenic kinase inhibitor, exclusively for 7 years, seek opportunities for additional funding and receive expert protocol assistance, according to the release.

“ ‘We are pleased with the orphan drug designation, as it confirms our belief in the versatility of ENMD-2076 as a promising treatment for HCC and for other tumor types that we are currently evaluating in the clinic,’ Ken K. Ren, PhD, chief executive officer of Casi Pharmaceuticals, said in the release. ‘Orphan drug status also enhances the commercial value of ENMD-2076 to treat HCC, a disease which is difficult to treat. We are finalizing our next steps for ENMD-2076 in HCC and/or in fibrolamellar carcinoma, a subset of HCC and for which there is no treatment available, and look forward to advancing our overall development plan for ENMD-2076.’ ”

FDA Grants Genentech’s Avastin Priority Review for Certain Types of Cervical Cancer

“Genentech, a member of the Roche Group (six:RO)(six:ROG)(otcqx:RHHBY), today announced that the U.S. Food and Drug Administration (FDA) has accepted the company’s supplemental Biologics License Application (sBLA) and granted Priority Review for Avastin® (bevacizumab) plus chemotherapy for the treatment of women with persistent, recurrent or metastaticcervical [sic] cancer.

“ ‘This regulatory application for Avastin is important because chemotherapy is the only approved treatment for women with metastatic, recurrent or persistent cervical cancer,’ said Sandra Horning, M.D., chief medical officer and head of Global Product Development. ‘Treatment with Avastin plus chemotherapy may help women with these conditions live longer than chemotherapy alone, and we look forward to working with the FDA on potentially making this medicine available to patients.’ ”

“The designation of Priority Review status is granted to medicines that the FDA believes have the potential to provide ‘significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions when compared to standard applications.’ The sBLA for Avastin plus chemotherapy in persistent, recurrent or metastaticcervical cancer is based on data from the Phase III GOG-0240 trial with an FDA action date of October 24, 2014.”

The gist: In the U.S., a drug must be approved by the U.S. Food and Drug Administration (FDA) in order for it to be prescribed to patients with specific diseases. Particularly promising drugs might be granted Priority Review, meaning that the FDA agrees to work with the drug manufacturer to accelerate the approval process. The drug Avastin (bevacizumab), already FDA-approved for several subtypes of several different cancers, was recently granted Priority Review status for the treatment of women with persistent, recurrent or metastatic cervical cancer. These patients currently only have the option of being treated with chemotherapy, but clinical trial evidence indicates that adding Avastin to the standard chemotherapy regimen might help these women live longer.

FDA Weighs Cancer Risk of Fibroid Removal Devices

“Federal health advisers say there is little to no evidence that a popular technique for removing fibroids can be performed without the risk of spreading undetected cancers to other parts of the body.

“The panel of Food and Drug Administration experts also said Friday that women who do undergo the procedure should sign a written consent form stating they understand the serious risks of laparoscopic power morcellation, in which electronic tools are used to grind tissue and remove it through a small incision in the abdomen.

“Surgeons developed the technique as an alternative to traditional surgery, which requires a larger incision that often results in more bleeding and longer hospital stays. But the FDA convened a two-day meeting this week after concluding that the risk of accidentally spreading undetected cancer to other organs may be far more common than previously thought.

“The agency asked its panel of obstetrics and gynecology experts to weigh in on potential methods for minimizing the risk, including using plastic specimen bags to catch bits of shredded tissue. Some surgeons already use that technique, but panelists said it is based on ‘intuition.’

” ‘There’s no evidence that the bags or any containment devices prevent the outcome we are trying to prevent,’ said Dr. Craig Shriver of the Walter Reed Medical Center.”

Bristol to Seek Melanoma Approval for Opdivo Ahead of Expectations

Editor’s note: Opdivo (aka nivolumab) is a drug that has shown promise for treating advanced melanoma in clinical trials with volunteer patients. The company that makes Opdivo, Bristol-Myers Squibb, has submitted an application to the U.S. Food and Drug Administration (FDA) that, if approved, would allow the company to market Opdivo to patients in the U.S. Opdivo is an immunotherapy treatment, meaning that it boosts a patient’s own immune system to fight cancer. Immunotherapies are a promising area of melanoma research, as described by our Chief Scientists on our Need to Know blog.

“Bristol-Myers Squibb Co said on Thursday it plans to seek U.S. marketing approval in the third quarter for its experimental cancer immunotherapy Opdivo as a treatment for advanced melanoma, which would be months sooner than Wall Street expected.

“The company said it would seek approval to market the drug to patients who had previously been treated with Bristol-Myers’ already approved melanoma drug Yervoy, which works through a different mechanism than Opdivo…

“Opdivo works by blocking a protein called PD-1, thereby enabling the immune system to recognize cancer cells and then attack them. It is considered one of Bristol-Myers’ most important experimental drugs, with potential to generate multibillion-dollar annual sales, if approved.”

FDA Grants Breakthrough Designation to Personalized Immunotherapy for ALL

“The FDA today granted breakthrough therapy designation for CTL019, an investigational personalized immunotherapy, for the treatment of relapsed and refractory adult and pediatric acute lymphoblastic leukemia, according to a press release issued by Penn Medicine.

“CTL019 (Novartis), developed by the University of Pennsylvania, is the first personalized cellular therapy for the treatment of cancer to receive this classification.

“In early-stage clinical trials conducted at the Hospital of the University of Pennsylvania and Children’s Hospital of Philadelphia, 89% of patients with ALL who were not responding to conventional therapies achieved complete remission after treatment with CTL019.

“ ‘Our early findings reveal tremendous promise for a desperate group of patients, many of whom have been able to return to their normal lives at school and work after receiving this new, personalized immunotherapy,’ Carl H. June, MD, director of translational research in the Abramson Cancer Center of the University of Pennsylvania. ‘Receiving the FDA’s Breakthrough Designation is an essential step in our work with Novartis to expand this therapy to patients across the world who desperately need new options to help them fight this disease.’ ”

Editor’s note: This story describes a new leukemia treatment called CTL019, which boosts a patient’s own immune system to fight cancer. CTL019 treatment is personalized for each patient, since it involves altering a patient’s immune system cells to attack tumor cells. It has been tested in volunteer patients in clinical trials, and has shown promising results for adults and children with relapsed or refractory acute lymphoblastic leukemia (ALL). The U.S. Food and Drug Administration (FDA) has now granted breakthrough therapy designation for CTL019, meaning that review and approval will be accelerated so that the drug can more quickly reach patients outside of clinical trials.