October 1, 2017 (Vol. 37, No. 17)

Industry Watch: As Blockbuster Hepatitis C Sales Sag, Gilead Goes Kite Fishing

With its Hepatitis treatments losing sales steam, Gilead Sciences is looking to cancer immunotherapies to drive future growth, hence its $11.9-billion deal to acquire Kite Pharma.

Kite is one of the two leading developers of chimeric antigen receptor T-cell (CAR-T) immuno-oncology treatments. And while Novartis was first across the proverbial finish line by winning FDA approval on August 30 for its CAR-T treatment Kymriah (tisagenlecleucel), Kite is expected to get a similar nod from the regulator for its axicabtagene ciloleucel (axi-cel), a treatment for relapsed or refractory aggressive non-Hodgkin’s lymphoma in patients who are ineligible for autologous stem cell transplant.

That may explain why Gilead is expected to hold onto as much of Kite as it can, according to one analyst.

“We believe Gilead will move aggressively to retain Kite employees, especially those in cell manufacturing, given manufacturing will be absolutely key for the axi-cel launch, and life of the product,” Canaccord Genuity Biotechnology Analyst John Newman, Ph.D., said in a note to investors. “We would absolutely expect Gilead to stay with Kite’s initial launch plan in terms of number of centers at launch and pace of adding new centers by [year-end] ‘18, even if FDA approves the product early in September or October 2017.”

The FDA has set a November 29, 2017 prescription drug user fee act (PDUFA) target action date. But a decision could come earlier, since Novartis won its Kymriah approval more than a month ahead of its early October PDUFA date.

Dr. Newman also cautioned that competitors—including Novartis and another CAR-T cancer therapy developer, Juno Therapeutics—may try to poach key Kite employees ahead of potential FDA approval for axi-cel.

Gilead expanded into hepatitis C drugs when it acquired Pharmasset for about $11 billion in 2011. Three years later, Gilead achieved blockbuster status for hepatitis C treatment Sovaldi (sofosbuvir), which was controversial because of its $84,000 list price.

Drug cost and competition lowered Sovaldi sales 24% last year, to $4.001 billion. Gilead also saw a year-over-year sales decline for hepatitis C drug Harvoni (ledipasvir 90 mg/sofosbuvir 400 mg) which dropped 34.5%, to $9.081 billion, due to larger discounts to insurers.

Discovery & Development: Antiviral Platform Looks to Broaden Its Horizons

Unlike antibiotics, which usually fight multiple pathogens, antivirals tend to follow a “one drug/one bug” approach. Consequently, antiviral development is fragmented. Candidate antivirals are narrowly targeted, in the sense they are developed against specific viruses, and they explore diverse mechanisms of action across distinct stages of the virus life cycle.

Fragmented development is expensive, particularly when it must, eventually, grapple with the problem of resistance. To prevent a viral infection from becoming resistant to treatment, antiviral regimens may incorporate multiple antivirals.

Antiviral development approaches that would attack multiple “bugs”—and thereby emphasize economy—are conceivable. Some researchers advocate the disruption of processes that are common across multiple viruses, such as the membrane fusion process. Other researchers focus on the host elements that participate in viral infections. Targeting host elements could increase the risk of side-effects, though perhaps this risk could be managed, if the targeted host elements were confined to host-pathogen interactomes.

Antiviral development could also emphasize economy by using common platforms to generate antiviral candidates against diverse viruses. This approach is being explored by Abivax, a French biotech that recently partnered with Evotec, a German contract research organization. Abivax intends to focus on discovering initial antiviral candidates, while relying on Evotec to optimize the candidates and perform early target development.

To identify antiviral candidates, Abivax uses an antiviral technology platform that targets mRNA biogenesis. This platform has already generated a chemical library of more than one thousand small molecules, including ABX464, the company’s Phase II candidate for reducing HIV reservoirs. The platform has also produced hits for human respiratory syncytial virus, influenza, and dengue.

Bioprocessing: MilliporeSigma Acquires Natrix Separations

MilliporeSigma said it will acquire Natrix Separations for an undisclosed sum; the purchase is designed to accelerate the buyer’s monoclonal antibody (mAb) and vaccine manufacturing offerings and complement its next-generation bioprocessing efforts through expansion of its single-use chromatography portfolio.

Based in Burlington, Ontario, Canada, Natrix provides hydrogel membrane products for single-use chromatography. Natrix markets both an anion-exchange membrane and cation-exchange membrane—and is developing additional products designed to help companies carry out fully single-use, full-scale biological purification processes.

The company says its technology platform can deliver high productivity and impurity removal in a single-use format, an ideal fit with next-generation processing.

That platform is designed to combine the high binding capacity, selectivity, and specificity normally associated with resin-based chromatography with the high throughput and ease of use of traditional membrane products.

Natrix says its technology enables highly selective chromatographic separations in many applications where no commercially viable separation process exists. Other advantages cited by the company are a 60–80% smaller footprint for processing, and the elimination of large, fixed glass columns.

“The Natrix technology platform, and the development options and capabilities that this brings for single-use and rapid cycling chromatography, will allow us to accelerate our offering in mAb and vaccine manufacturing,” MilliporeSigma CEO Udit Batra, Ph.D., said in a statement. “This acquisition creates tremendous opportunity to drive growth and advancement in next-generation processing—an area of increasing importance to our customers.”

MilliporeSigma—the life science business of Merck KGaA—defines next-gen processing as any technology, expendable, or system that changes the existing mAb manufacturing template through an evolution of unit operation intensification, connecting processes, resulting in a fully continuous process. 

Molecular Diagnostics: PCR-Based Liquid Biopsy Is a Simple and Sensitive Cancer Diagnostic

Noninvasive cancer diagnostics are rapidly becoming an essential part of precision medicine therapies. These cutting-edge assays are not only useful in the preliminary diagnosis of various cancerous conditions, but also help physicians track the progression of cancers during and after treatment. Typically, these tests have employed the use of next-generation sequencing (NGS) techniques; while they are sensitive, they are also complicated and costly. Now, a team of investigators from Stanford University has just released findings from their work on a new type of test that can detect genetic mutations in minute amounts of DNA released from cancer cells into the blood using a relatively simple PCR-based assay. 

The results from this study— published in The Journal of Molecular Diagnostics in an article entitled, “Single-Color Digital PCR Provides High-Performance Detection of Cancer Mutations from Circulating DNA”—show that this highly sensitive test has the potential to be personalized to recognize mutations unique to any individual cancer. The test, which the researchers dubbed “single-color digital PCR”, requires only a fraction of a tube of blood and can detect as few as three mutation-bearing molecules in a single reaction.

“For monitoring patient tumors, only a handful of blood tests are available that are limited to only several types of cancers,” explained senior study investigator Hanlee Ji, M.D., associate professor in the department of medicine at Stanford University and senior associate director of the Stanford Genome Technology Center. “Nearly all cancer patients require monitoring by whole-body imaging, which can be costly, complex, and time-consuming.”

In the study, the researchers described the use of the test to analyze samples from six patients. Of these patients, five were previously diagnosed with colorectal cancer and one with bile duct cancer. The research team was able to identify tumor-derived circulating DNA from three out of six patients. In one patient, the assay showed the presence of three different mutations. The three patients, whose samples did not show elevated cancer DNA, were undergoing active treatment at the time of collection.

“Molecular tests like the one we have developed will enable patients to be monitored at every visit, and thus have the potential for quickly tracking cancer growth and spread,” Dr. Li noted. “Moreover, the test’s rapid turnaround and relatively low cost, especially compared to next-generation DNA sequencing, provide a potential opportunity for universal monitoring of more patients than is currently done.”

The single-color digital PCR test offers several advantages over other methods of circulating tumor DNA analysis, such as next-generation targeted sequencing and fluorescent probe-based digital PCR assays. The main advantage is that the new technique does not rely on preamplification, which can introduce errors and biases. And, due to the speed of the assay and its reduced costs, the research team is hopeful that their test could be employed in an array of physician’s offices and clinics for routine cancer monitoring. 

“This test is simple enough to set up and analyze without extensive training, and, therefore, it can be implemented by anyone, making it highly accessible to any laboratory,” concluded lead study author Christina Wood-Bouwens, who is a research professional at Stanford University School of Medicine.

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