Replies to post #148306 on NorthWest Biotherapeutics Inc (NWBO)

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I did get the chance to listen to the entire presentation. There wasn't really anything new and riveting in the testimony there.

There was something worth noting and I don't think it was noted on this board yet.

One of the senators asked Dr. Gottlieb about a laboratory test that received approval. It had been given breakthrough designation, and it was given simultaneous CMS coverage at the same time (which is new, I guess).

Anyhow... this laboratory test approval is for F1CDx by Foundation Medicine. Why this seems relevant to me is that their test is for genetic mutations to help identify which treatments might be best for patients. And there has been a lot of talk about the importance of such tests in the future treatment of GBM.

FDA Announces Approval, CMS Proposes Coverage of First Breakthrough-designated Test to Detect Extensive Number of Cancer Biomarkers
FDA approves test to detect mutations in 324 genes, two genomic signatures. Second to be approved with proposed coverage under FDA/CMS Parallel Review Program.

The U.S. Food and Drug Administration today approved the FoundationOne CDx (F1CDx), the first breakthrough-designated, next generation sequencing (NGS)-based in vitro diagnostic (IVD) test that can detect genetic mutations in 324 genes and two genomic signatures in any solid tumor type. The Centers for Medicare & Medicaid Services (CMS) at the same time proposed coverage of the F1CDx. The test is the second IVD to be approved and covered after overlapping review by the FDA and CMS under the Parallel Review Program, which facilitates earlier access to innovative medical technologies for Medicare beneficiaries.

“By leveraging two policy efforts aimed at expediting access to promising new technologies, we’ve been able to bring patients faster access to a breakthrough diagnostic that can help doctors tailor cancer treatments to improve medical outcomes and potentially reduce health care costs,” said FDA Commissioner Scott Gottlieb, M.D. “The FDA’s Breakthrough Device Program and Parallel Review with CMS allowed the sponsor to win approval for this novel diagnostic and secure an immediate proposed Medicare coverage determination within six months of the FDA receiving the product application.”

Compared to other companion diagnostics previously approved by the FDA that match one test to one drug, the F1CDx is a more extensive test that provides information on a number of different genetic mutations that may help in the clinical management of patients with cancer. Additionally, based on individual test results, the new diagnostic can identify which patients with any of five tumor types may benefit from 15 different FDA-approved targeted treatment options. Its results provide patients and health care professionals access to all of this information in one test report, avoiding duplicative biopsies.

“The F1CDx can help cancer patients and their health care professionals make more informed care decisions without the often invasive process of extracting tumor samples multiple times to determine eligibility for a single treatment or enrollment in a clinical trial,” said Jeffrey Shuren, M.D., director of the FDA’s Center for Devices and Radiological Health (CDRH). “With the run of one test, patients and health care professionals can now evaluate several appropriate disease management options.”

Today, CMS also issued a proposed national coverage determination of the F1CDx and other similar NGS IVDs for Medicare beneficiaries with advanced cancer (i.e., recurrent, metastatic or advanced stage IV cancer), who have not been previously tested using the same NGS technology and continue to seek further cancer therapy. The proposed national coverage determination provides coverage of NGS IVD tests to assist patients and their treating physicians in making informed cancer treatment decisions that improve health outcomes. Use of a test as a diagnostic also includes the ability to help patients and their treating physicians determine candidacy for cancer clinical trials.

“Through parallel review and collaboration, we speed access to innovative diagnostics, so that doctors are better able to deliver the best quality care to their patients and patients have access to these state-of-the-art tests,” said Seema Verma, Administrator of CMS. “Our proposal establishes clear expectations, while at the same time delivering better outcomes for the people we serve.”

This determination was made under the FDA-CMS Parallel Review Program, where the agencies concurrently review medical devices to help reduce the time between the FDA’s approval of a device and Medicare coverage. This voluntary program is open to certain premarket approval applications for devices with new technologies and to medical devices that fall within the scope of a Part A or Part B Medicare-benefit category and have not been subject to a national coverage determination.

The F1CDx detects gene mutations that may be found in any solid tumor and this information can be used by physicians according to professional guidelines to manage cancer patients. Moreover, it can be used as a companion diagnostic to identify patients with specific mutations who may benefit from certain FDA-approved treatments for non-small cell lung cancer, melanoma, breast cancer, colorectal cancer or ovarian cancer. Importantly, the F1CDx can detect genetic mutations that are indicated for multiple FDA-approved treatments, which extends beyond the previous “one test for one drug” model.

The device works by sequencing DNA from a patient’s tumor sample to determine the presence of gene mutations and alterations. It also detects certain molecular changes (microsatellite instability and tumor mutation burden). Clinical performance of the test was established through a least burdensome means by comparing the F1CDx to previously FDA-approved companion diagnostic tests that are currently used to determine patient eligibility for certain treatments. Results indicated that the test’s ability to detect select mutation types (substitutions and short insertions and deletions) representative of the entire 324 gene panel is accurate approximately 94.6 percent of the time.

The F1CDx had not been previously submitted for the FDA’s review because it is a laboratory-developed test, for which the agency has generally not enforced premarket review and other applicable requirements. However, at the test developer’s request, the FDA worked closely with them to help enter it into the agency’s newly established Breakthrough Device Program. Because of the test’s potential to consolidate multiple companion diagnostic claims for patients and health care providers in a single test, the F1CDx was granted Breakthrough Devicedesignation. Under the Breakthrough Device Program, the FDA provides intensive interaction and guidance to the company on efficient device development, which expedites evidence generation and the agency’s review of devices that provide for more effective treatment or diagnosis for life-threatening or irreversibly debilitating diseases for which no approved or cleared treatment exists or that offer significant advantages over the existing standard of care.

The FDA also reviewed the F1CDx application using a coordinated, cross-agency approach; the clinical review was conducted by FDA’s CDRH with support from FDA's Oncology Center of Excellence, while all other aspects of review and the final product approval determination was conducted by the FDA’s CDRH.

The FDA granted approval for the F1CDx test to Foundation Medicine, Inc.

www.practiceupdate.com/c/61478/1/12/?elsca1=emc_enews_daily-digest&elsca2=email&elsca3=practiceupdate_onc&elsca4=oncology&elsca5=newsletter&rid=MjU5OTIzOTQ4MTYxS0&lid=10332481

So I took a quick look at Foundation Medicine's website. A quick look at the FoundationOne "Genomic Testing" link - given below - indicates that this flagship assay is for solid tumor cancers including but not limited to: Non-Small Cell Lung Cancer (NSCLC), Colorectal, Breast, Ovarian, and Melanoma.

They feature two clinical studies that are as follows:
Tumor Mutational Burden as an Independent Predictor of Response to Immunotherapy in Diverse Cancers
and
Clinical utility and treatment outcome of CGP in high-grade glioma

Clinical utility and treatment outcome of comprehensive genomic profiling in high grade glioma patients.

Blumenthal DT1,2, Dvir A3, Lossos A4, Tzuk-Shina T5, Lior T6, Limon D7, Yust-Katz S8,7, Lokiec A5, Ram Z8,9, Ross JS10,11, Ali SM10, Yair R3, Soussan-Gutman L3, Bokstein F12,8.
Author information
Abstract
Genomic research of high grade glioma (HGG) has revealed complex biology with potential for therapeutic impact. However, the utilization of this information and impact upon patient outcome has yet to be assessed. We performed capture-based next generation sequencing (NGS) genomic analysis assay of 236/315 cancer-associated genes, with average depth of over 1000 fold, to guide treatment in HGG patients. We reviewed clinical utility and response rates in correlation to NGS results. Forty-three patients were profiled: 34 glioblastomas, 8 anaplastic astrocytomas, and one patient with anaplastic oligodendroglioma. Twenty-five patients were profiled with the 315 gene panel. The median number of identified genomic alterations (GAs) per patient was 4.5 (range 1-23). In 41 patients (95?%) at least one therapeutically-actionable GA was detected, most commonly in EGFR [17 (40?%)]. Genotype-directed treatments were prescribed in 13 patients, representing a 30?% treatment decision impact. Treatment with targeted agents included everolimus as a single agent and in combination with erlotinib; erlotinib; afatinib; palbociclib; trametinib and BGJ398. Treatments targeted various genomic findings including EGFR alterations, mTOR activation, cell cycle targets and FGFR1 mutations. None of the patients showed response to respective biologic treatments. In this group of patients with HGG, NGS revealed a high frequency of GAs that lead to targeted treatment in 30?% of the patients. The lack of response suggests that further study of mechanisms of resistance in HGG is warranted before routine use of biologically-targeted agents based on NGS results.

This indicates to me there must be a fairly high level of interest in profiling gliomas - and if DCVax-L were approved, it could be used to determine whether this treatment would work more effectively on the patient's GBM, depending upon the type.

Anyhow, I did think this merited a mention.

Also, Dr. Lamar Alexandar, of Tennessee (home of Cognate) the Chairman of the Senate Health, Education, Labor and Pensions Committee, and the Senate Sponsor of the 21st Century Cures Act, had this to say to Dr. Gottlieb at minute 56:15:

Well I’m out of time but as we continue our oversight, and I’m sure you’re going to do this, we need to think of this as a seamless process. We need to go from idea to the doctor’s office to the patient. And we need to get through the F… through the research and into the FDA, through CMS, to make these things work. And I hope you’ll pay a great deal of attention to that.