On April 08, 2016 PharmaCyte Biotech, Inc. (OTCQB:PMCB), a clinical stage biotechnology company focused on developing targeted treatments for cancer and diabetes using its signature live-cell encapsulation technology, Cell-in-a-Box, reported that the encapsulation facility located in Bangkok, Thailand, that will be used to encapsulate the live cells used for PharmaCyte’s pancreatic cancer therapy has recently been inspected by the Food and Drug Administration of Thailand (Thai FDA) (Press release, PharmaCyte Biotech, APR 8, 2016, View Source [SID:1234510768]). In its report on that inspection, the Thai FDA stated that, "The facility is built according to the pre-approved floor plan and is now deemed suitable for the manufacture of pharmaceutical products."

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PharmaCyte Biotech’s Chief Executive Officer, Kenneth L. Waggoner, commented, "We are very pleased that our partner, Austrianova, has received a positive opinion from the Thai FDA for Austrianova’s live-cell encapsulation facility. This is an important milestone in the development of PharmaCyte’s treatment for pancreatic cancer and a pre-requisite for our upcoming pancreatic cancer clinical trial."

The main role of the Thai FDA is to protect consumer’s health, especially, to ensure safety, quality and efficacy of health products within its purview. These products include: foods, drugs, psychotropic substances, narcotics, medical devices, volatile substances, cosmetics and hazardous substances. It is an absolute requirement that the construction and operation of Austrianova’s live-cell encapsulation facility be in accordance with both Thai national legislation as well as international agreements.

PharmaCyte’s product for pancreatic cancer will be manufactured in Austrianova’s facility in Bangkok. It consists of live human cells that have been genetically engineered to convert the anticancer prodrug ifosfamide into its "cancer-killing" form and then encapsulated using the Cell-in-a-Box encapsulation technology. In PharmaCyte’s upcoming clinical trial, these encapsulated live cells will be used with low doses of ifosfamide (one third the normal dose) as a "consolidation therapy" with the current standard of care for advanced pancreatic cancer when a patient no longer benefits from first line therapy. PharmaCyte’s therapy will be compared with the combination of the anticancer drug capecitabine plus radiation in patients with locally advanced, non-metastatic, inoperable pancreatic cancer whose tumors are stable or progressing after 4-6 cycles of treatment with either the combination of Abraxane plus gemcitabine or the four-drug combination known as FOLFIRINOX.

On April 8, 2016, iCAD, Inc., (Nasdaq: ICAD), an industry-leading provider of advanced image analysis, workflow solutions and radiation therapy for the identification and treatment of cancer, reported that its mammography Computer Aided Detection (CAD) solution is now available on Fujifilm’s Aspire Cristalle full field digital mammography system (Press release, Fujifilm, APR 8, 2016, View Source [SID:1234510617]).

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"iCAD is pleased to provide our leading mammography CAD solution to Fujifilm’s Aspire Cristalle customers worldwide. We trust our integrated solutions will now provide radiologists with a clinical decision support tool designed to help provide the highest quality care for mammography patients", said Diane Clifford, director of marketing for cancer detection solutions at iCAD.

The PowerLook Advanced Mammography Platform is a flexible solution supporting iCAD’s industry leading computer-aided detection algorithm for digital mammography that assists radiologists in the detection of breast cancer. The iCAD solution is used by more than 3,000 mammography facilities worldwide.

"Fujifilm is happy to have reached this important milestone with iCAD, moving our customers another important step forward with the ability to simplify the reading of digital mammography exams" said Rob Fabrizio, director of marketing and product development at FUJIFILM Medical Systems U.S.A., Inc. "We trust our customers will be pleased with this coupling of the most requested CAD platform with the exceptional imaging capabilities of our Aspire Cristalle mammography system."

Fujifilm is constantly working to develop the most advanced digital mammography systems, to assist in the early detection of breast cancer. Aspire Cristalle brings together Fujifilm’s extensive research, expertise and experience. The unique platform allows easy upgradability to future technologies, while offering optimal imaging of all breast types at lower dose. The Aspire Cristalle will be on display at the National Consortium of Breast Centers (NCoBC) conference from April 9-13, 2016 in Las Vegas, NV.

The FDA today raised a host of thorny issues for an upcoming advisory committee meeting scheduled to review Clovis Oncology’s ($CLVS) application for an accelerated approval of its non-small cell lung cancer drug rociletinib (Article, FierceBiotech, APR 8, 2016, View Source [SID:1234510595]).

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In an internal review released Friday morning, the agency noted that it wants its group of outside experts to consider whether rociletinib is better than existing drugs on the market, offered its opinion that serious safety issues associated with the drug will require a "black box" warning to patients and added that the agency challenged the company’s use of unconfirmed responses in its data on the drug last fall.

The comparison the FDA is asking for will pit rociletinib directly against AstraZeneca’s Tagrisso, which won an approval last year based on an overall response rate of 59%, far above the final 32% mark that the Boulder, CO-based company has posted for a 625-mg dose of its drug. Tagrisso and rociletinib both inhibit EGFR and are designed to target lung cancers with a T790M mutation.

The agency’s review also notes serious adverse events in the rociletinib studies, singling out hyperglycemia and QTc prolongation leading to Torsades de pointes–a lethal irregular heart rhythm–which should require the black box warning if the drug is allowed on the market.

Significantly, the review includes a timeline on the interactions between the FDA and Clovis execs for this drug, which won the agency’s breakthrough drug designation based on an overall tumor response rate that was reported early on at more than 50%. By last June, though, the response rate reported by the company for its 500-mg dose was 38%.

Then, on November 9, the FDA noted: "During the Mid-Cycle Communication with Clovis, FDA provided an update of the status of the review and communicated significant issues arising from the review. The FDA stated its disagreement with Clovis’ reported efficacy results of the pooled analysis for Studies CO-1686-008 and CO-1686-019. The disagreement was based on Clovis’ inclusion of patients with unconfirmed responses in the efficacy assessment."

Clovis admitted that it was using unconfirmed responses and submitted an update that required a three-month extension of the FDA review. Several days later, the company updated its data for investors, triggering a collapse of its stock price and sparking outrage among its investors over the company’s timing.

In a word, concluded Stifel, the FDA review is "awful" for Clovis. "We think the drug is dead," noted their analysts, with regulators likely looking to stiff-arm the drug until Tiger-3 data are ready in 2018. That would leave Clovis spending a huge sum on a drug with little or no upside on the market. Clovis is likely to stop all studies, Stifel projected, except for a PD-L1 combination that could open a door to a workable combination therapy.

At the beginning of this week, noted cancer drug development expert Kapil Dhingra stirred considerable discussion with a new analysis which questions Clovis’s use of unconfirmed data long after most investigators would have nailed down a final confirmed response. In an interview with FierceBiotech, he charged the company with misrepresenting its data.

"I feel that the efficacy data have, consistently and repeatedly, over many years, been misrepresented," Dhingra told me earlier. "This is not simply a case of gray zones, this is black and white untrue presentation of the data. And it is not just a minor misrepresentation (such as photoshopping a western blot image etc that can get a basic scientist in trouble); the true efficacy is about half of what they represented."

Typically, the FDA’s cancer advisory group would limit themselves to a conversation devoted to a drug’s risk/benefit profile. Recently, practically any drug that offered a clinical benefit could expect an endorsement, even with serious safety issues. But this time around the FDA may be setting the stage for putting off an approval and waiting for confirmatory study data, or at the very least leaving the drug seriously hobbled in a head-to-head market fight with a competitor.

That’s all something that the FDA advisers will get a chance to comment on next Tuesday. It’s also a subject that FDA cancer czar Richard Pazdur could address. I asked him by email earlier this week if he plans to attend the AdComm next week, and in a one-word reply he responded "yep."

Increased bioavailability of phenylephrine is reported when combined with paracetamol in over-the-counter formulations for the symptomatic treatment of the common cold and influenza. Such formulations could increase phenylephrine-related cardiovascular adverse events particularly in susceptible individuals. Quantification of the effect of phenylephrine concentration on blood pressure allows simulation of potential adverse combination therapy effects.
MEDLINE and EMBASE databases were searched for papers discussing or describing any adverse effect, hypersensitivity or safety concerns related to phenylephrine alone or in combination with other drugs. The pharmacodynamic relationship between plasma phenylephrine concentration and mean arterial blood pressure was characterized using published observations of blood pressure changes after ophthalmic eye drops. The resulting pharmacokinetic and pharmacodynamic parameters were then used to predict mean arterial blood pressure (MAP) changes in that population if given an oral combination of phenylephrine and paracetamol.
There were 1172 papers identified for examination. Forty-seven reports fulfilled the inclusion criteria. Increases in blood pressure and decreases in heart rate have been reported with doses over 15 mg. It has been estimated that a 20-mmHg increase in systolic blood pressure would occur with an oral dose of 45 mg phenylephrine in normotensive healthy people. Those taking monoamine oxidase inhibitors report increased systolic blood pressure of greater than 60 mmHg. Blood pressure and heart rate changes are potentiated in patients with underlying hypertension. Simulation showed a modest increase in MAP when phenylephrine 10 mg was co-administered with paracetamol 1 g (4.2 vs 12.3 mmHg).
Combination paracetamol phenylephrine oral therapy has potential to increase blood pressure more than phenylephrine alone in those with cardiovascular compromise.

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H.P. Acthar Gel (Acthar) is a highly purified repository gel preparation of adrenocorticotropic hormone (ACTH1-39), a melanocortin peptide that can bind and activate specific receptors expressed on a range of systemic lupus erythematosus (SLE)-relevant target cells and tissues. This study was performed to evaluate the effects of Acthar in a mouse model of SLE, using an F1 hybrid of the New Zealand Black and New Zealand White strains (NZB/W F1). Twenty-eight week old NZB/W F1 mice with established autoimmune disease were treated with Acthar, Placebo Gel (Placebo), or prednisolone and monitored for 19 weeks. Outcomes assessed included disease severity (severe proteinuria, ≥ 20% body weight loss, or prostration), measurement of serial serum autoantibody titers, terminal spleen immunophenotyping, and evaluation of renal histopathology. Acthar treatment was linked with evidence of altered B cell differentiation and development, manifested by a significant reduction in splenic B cell follicular and germinal center cells, and decreased levels of circulating total and anti-double-stranded DNA (IgM, IgG, and IgG2a) autoantibodies as compared with Placebo. Additionally, Acthar treatment resulted in a significant decrease of proteinuria, reduced renal lymphocyte infiltration, and attenuation of glomerular immune complex deposition. These data suggest that Acthar diminished pathogenic autoimmune responses in the spleen, peripheral blood, and kidney of NZB/W F1 mice. This is the first preclinical evidence demonstrating Acthar’s potential immunomodulatory activity and efficacy in a murine model of systemic lupus erythematosus.
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