Eli Lilly (LLY) and Incyte (INCY) confirmed earlier that the U.S. FDA has approved the 2-mg dose of Olumiant, a once-daily oral medication for the treatment of adults with moderately-to-severely active rheumatoid arthritis who have had an inadequate response to one or more tumor necrosis factor inhibitor therapies. Lilly said it will launch Olumiant in the U.S. by the end of the second quarter of 2018. The price of Olumiant will be 60% less than the leading TNF inhibitor, noted Lilly, which will also be offering a patient support program, “Olumiant Together.” Incyte is now eligible to receive a $100M milestone payment from Lilly as a result of the Olumiant approval, which Incyte expects to recognize in the second quarter of 2018
Friday, June 1, 2018
ASCO 2018: Extending the Reach of Precision Medicine
The 54th annual meeting of the American Society of Clinical Oncology (ASCO) will once again feature the latest news, information, and data about advances in clinical cancer, but the program content also reflects a desire to broaden the reach of those advances and ensure that the maximum number of patients derive maximum benefit.
With a working theme of “Delivering Discoveries: Expanding the Reach of Precision Medicine,” ASCO will provide the venue for more than 2,500 research abstracts that will be reported during the meeting. An additional 3,350 abstracts were accepted for publication online. Beyond conventional basic and clinical research, a substantial portion of the program will be devoted to issues such as access to care; social, economic, and clinical disparities; use of technology to broaden the reach of cancer care and make it more efficient; greater emphasis on patient-reported outcomes and shared decision-making; and caring for the growing population of cancer survivors.
“The promise of precision medicine is only as good as our ability to make these treatments available to all patients,” said ASCO President Bruce E. Johnson, MD.
Recent advances in cancer research, and their subsequent translation into clinical practice, have had a transformative effect on the way cancer is treated. In a video developed for the 2018 annual meeting, Johnson talked about how advances that began in laboratories often have evolved into life-changing experiences for patients. He said that as a lung cancer specialist, his personal favorite is the discovery that mutations in the EGFR gene drive the progression of cancer in some patients, a development that for the first time allowed many patients to be treated with a pill instead of chemotherapy.
One example of potential practice-changing clinical research at this year’s meeting has already emerged: A study showing that 6 months of adjuvant trastuzumab (Herceptin) is at least as effective as the standard-of-care 12 months for women with HER2-positive breast cancer, causes less cardiac toxicity, and costs less.
Something for Everyone
Oncology practitioners look forward to ASCO for a variety of reasons. Heading the list for many attendees are the opportunities to learn about new research, attend discussions and lectures by leaders in the field of oncology, and participate in interactive sessions to exchange information and ideas.
“I like to attend ASCO each year because it allows me to think about the new data presented and have vibrant discussions with colleagues in terms of how we can use this data to establish great practice patterns that may best benefit our cancer patients,” said Daneng Li, MD, of City of Hope in Duarte, Calif.
One study in particular caught Li’s attention: A randomized trial showing improved progression-free survival in patients with pancreatic neuroendocrine tumors treated with temozolomide and capecitabine instead of temozolomide alone.
Gynecologic oncologist Rebecca Arend, MD, of the University of Alabama at Birmingham, said she is attracted to several studies in ovarian cancer: the value of secondary debulking in platinum-resistant disease, retreating patients with bevacizumab (Avastin), and long-term survival data from a study of upfront treatment with bevacizumab. A session on developmental therapeutics in immunotherapy and another on emerging therapeutics in gynecologic cancers also hold special interest for her.
“ASCO, for me as a physician-scientist, is a meeting where the basic science is all extremely relevant to patient care and the data presented helps shape how we should treat our patients in the future,” she said. “More importantly, it provides platforms for discussions about understanding where the field is going and what we should be exploring further in order to better focus our research effectors in the lab and in clinical trials.
“In addition, clinicians have always been extremely collaborative and traditionally keep the focus on helping the patients and improving survival of the cancer survivors that we see in clinic and in our practice, which makes ASCO a very productive and important meeting for me.”
Connecting, Reconnecting, Affirming
Hossein Borghaei, DO, a lung cancer specialist at Fox Chase Cancer Center in Philadelphia, said he is looking forward to hearing the results of a late-breaking study comparing the PD-1 inhibitor pembrolizumab (Keytruda) with standard platinum-based chemotherapy as first-line treatment for patients with advanced non-small cell lung cancer and different levels of PD-L1 expression.
“This study potentially could affect what we do in the clinic, if it shows a benefit for single-agent immunotherapy,” he said. “This study will be included in the plenary session, and to be included in an ASCO plenary session is a big deal, indicating that a study is important.”
Several studies of immunotherapy-containing combinations for lung cancer will likely attract a lot of interest among lung cancer specialists, he added. Updated information on some previously reported clinical trials also will provide anticipated information that might readily apply to clinical practice, particularly mature data from studies involving targeted therapies.
“Some of these studies have the potential to change clinical practice, and others may affirm what we are already doing,” said Borghaei, who will also moderate an education session about strategies for treating patients with lung cancers that are not molecularly driven (without EGFR, ALK, or ROS1 mutations, for example).
Borghaei said that as a frequent attendee of ASCO, he has found that the meeting also affords opportunities for interactions that go beyond scientific research and clinical practice: “It’s a good way to reconnect with colleagues and friends, establish collaborations, and affirm existing connections with people you know.”
Two studies in advanced/metastatic renal cell carcinoma (RCC) head the list of new research on the radar of genitourinary cancer specialist Elizabeth Plimack, MD, also of Fox Chase Cancer Center. One study showed an “impressive response rate” with the immune checkpoint inhibitor pembrolizumab as first-line therapy for patients with advanced clear-cell RCC.
The second study provided insight into patient-reported outcomes (PROs) for treatment with the combination of a VEGF inhibitor and another immune checkpoint inhibitor for metastatic RCC.
“This trial shows better overall PROs with the combination of bevacizumab and atezolizumab [Tecentriq] versus sunitinib [Sutent],” said Plimack. “This refutes the dogma that combination therapy typically leads to higher side effects compared with monotherapy.”
The meeting continues here through Tuesday, and MedPage Today will have comprehensive coverage of the news and developments.
US-China Xynomic preps broad push for HDAC cancer drug after new financing
U.S.-China biotech Xynomic Pharma has raised additional funding to take an HDAC inhibitor in-licensed last year into seven new cancer trials.
The company hasn’t revealed the amount of the series B financing but says it will be enough to start trials of abexinostat—originally developed by Pharmacyclics—in blood cancers and solid tumors over the next 12 months. It will also fund initial clinical testing of XP-102, a pan-RAF inhibitor licensed from Boehringer Ingelheim in a $502 million deal last November, in colorectal cancer and melanoma.
Four of the seven abexinostat trials will be pivotal studies that could support registration, saysXynomic, including a multicountry study testing the drug as a monotherapy for follicular lymphoma and a similar trial in China. The other pivotal studies include a Chinese trial of abexinostat in diffuse large B-cell lymphoma (DLBCL) and a multicountry combination trial pairing the drug with Novartis’ Votrient (pazopanib) in patients with locally advanced or metastatic renal cell carcinoma.
The other three nonpivotal studies include a phase 1/2 assessment of abexinostat with Johnson & Johnson’s Imbruvica (ibrutinib) in DLBCL and mantle cell lymphoma, a phase 1b trial of the drug alongside Merck & Co.’s Keytruda (pembrolizumab) in multiple solid tumors, and a combination study in estrogen receptor-positive breast cancer.
Xynomic acquired exclusive rights to abexinostat in February 2017, without revealing any financial details or even who it had licensed the drug from. While Pharmacyclics originated the drug, it was initially licensed to French drugmaker Servier, which gave back rights to it in 2014 ahead of Pharmacyclics’ $21 billion takeover by AbbVie the following year.
The HDAC inhibitor class has come under pressure of late after an ASCO abstract for one of the leaders in the category, Syndax’s entinostat, revealed less-than-stellar results in a Keytruda combination trial which spooked investors and led to a dip in the company’s share price.
Meanwhile, Xynomic says it launched a dedicated R&D center in Shanghai last month that will focus on the discovery and early-stage development of small-molecule drugs focused on kinase inhibition, immuno-oncology and epigenetic modification. It’s already working on two candidates, says the biotech, namely XP-103, a TRK/Fra-1 inhibitor, and XP-104, a RET inhibitor.
Northern Light Venture Capital, Zhongshan Bison Healthcare Investment and Hakim Unique Internet Company led the round, with Xynomic’s existing investors—including Prosperico Ventures and the company’s founder and chairman Yinglin Mark Xu—also taking part.
Small molecule quells cancer-driving RNA, previously undruggable targets
Despite all the excitement gene-editing systems like CRISPR have generated, there have been challenges when it comes to delivering the technology. Viral vectors are commonly used but can lead to off-target editing and side effects such as cancer. Researchers from The Scripps Research Institute have been working on an alternative: a small molecule that can selectively target RNA and could pave the way to a pill that can treat genetic diseases.
DNA-targeting CRISPR has dominated the gene editing landscape, but RNA-focused systems are on the rise. These systems target RNA to bring about reversible changes to DNA, but are delivered in much the same way—via injection.
Matthew Disney, a professor at Scripp’s Florida campus, has been working on small molecules that target RNAs, which have historically been considered undruggable due to their small size and relative lack of stability. What’s more, it is difficult to selectively target RNAs because they are made of just four ingredients: the nucleotide bases A, T, G and C. Proteins, on the other hand, are composed of many different amino acids.
Disney’s approach combines an RNA-degrading enzyme with a druglike molecule that binds selectively to a specific RNA. The complex, dubbed RIBOTAC (ribonuclease-targeting chimeras) is designed to latch onto and destroy an “undesirable gene product,” such as a disease-causing RNA, according to a statement from Scripps.
The team tested their technology against miRNA-96, a microRNA oncogene that fosters cancer cell proliferation. They tethered the RNA-degrading enzyme RNase L to Targaprimir-96, a molecule they created in 2016 to bind with miRNA-96. The treatment selectively cleaved the miRNA-96 precursor in cancer cells, silencing the oncogene. It “derepressed” the transcription factor FOXO1, unleashing cell death in triple-negative breast cancer cells, but not in healthy breast cells. The findings appearin the Journal of the American Chemical Society.
Others have tried to target RNA with an antisense approach, using strands of DNA or RNA to knock down specific molecules of RNA and treat disease. Ionis Pharma has licensed out antisense treatments to Roche, AstraZeneca and Janssen in deals targeting Huntington disease, kidney disease and gastrointestinal disease, for example.
On the flip side, Accent Therapeutics launched this year to drug RNA-modifying proteins (RMPs), which have been linked to certain cancers. The biotech is working to understand which proteins are involved in which cancer indications and to identify the patients who would be most likely to respond to treatment.
Accent has selected 20 RMPs it believes have “strong implications” in specific cancer indications and prioritized them according to unmet medical need and what it knows about the biology of those targets, including whether they are likely to be a druggable. Of these, it has picked four targets and is working to identify chemical matter for each one, Chief Scientific Officer Robert Copeland told FierceBiotech.
Awakening the body’s ability to kill its own cancer by exploiting cells’ RNA degradation system offers a novel approach to attacking cancer, says Disney of Scripps.
Scripps intends to apply its technology to hard-to-treat cancers, genetic disorders and other diseases for which there are no known cures. “The applications range from cancer to incurable disease—basically any disease where RNA is a key driver,” Disney told FierceBiotechResearch in an email.
STAAR Surgical (STAA) Short Interest Update
STAAR Surgical (NASDAQ:STAA) was the recipient of a large decline in short interest during the month of May. As of May 15th, there was short interest totalling 494,547 shares, a decline of 49.1% from the April 30th total of 971,594 shares. Approximately 1.2% of the shares of the stock are short sold. Based on an average daily trading volume, of 872,862 shares, the short-interest ratio is currently 0.6 days.
Amgen latest drugmaker with Herceptin biosimilar sidelined by FDA letter
Amgen, in a two-sentence announcement today, said it received a complete response letter for the biosimilar of Roche’s cancer med Herceptin it developed with Allergan. It marks the third Herceptin biosimilar that has been stalled by the FDA but has won approval in Europe.
The Thousand Oaks, California-based drugmaker offered no insight into what the FDA found lacking in its version. “We will work closely with the FDA to bring this important medicine to patients in the U.S. We do not expect this to impact our U.S launch plan,” it said in the announcement.
Biosimilar makers have been hot to develop their own versions of Roche’s Herceptin, a long-in-the tooth oncology drug that still raked in $2.5 billion in U.S. sales last year and $7 billion worldwide. Mylan and partner Biocon, Pfizer and now Amgen have all had their initial applications rejected by U.S. regulators. Pfizer just today won an European Medicines Agency approval for its Trazimera.
None of the drugmakers have provided much detail as to what triggered their CRLs, so it is unknown whether there has been a common theme for the denials or what the hangup is for the FDA that has not bothered the EMA. FDA concerns about Biocon’s Indian plant figured into the rejection of the version from Mylan and its Indian partner.
Mylan and Biocon won an FDA thumbs-up for their Herceptin biosimilar in December, but only after a three-month delay in which the FDA looked over some new technical data that had resulted from changes made in their manufacturing operations. When the partners got their CRL it looked like they would go from the front of the line to the back of the line as the FDA considered applications from other drugmakers. But the partners ended up being the first to win approval as competitors also had their versions sidelined.
These delays have allowed Roche to continue to go to the Herceptin cash machine. Despite recent approvals for biosimilars in the EU, Herceptin sales worldwide were up 3% last year to about $7 billion on higher sales in the U.S. and Brazil. While most of those sales come from the U.S., $2.7 billion, EU revenue is also significant, at $2.1 billion.
While regulatory and manufacturing stumbles have protected Roche’s Herceptin sales, the Swiss drugmaker is also throwing up roadblocks. Last fall, Roche sued Pfizer for infringement on 40 Herceptin patents, asking a court to block a potential biosim launch. Pfizer said it will defend its “position vigorously and in the appropriate venue.”
Medtronic recalls HeartWare HVAD over electrical disconnection
Medtronic is recalling the HeartWare HVAD because of the possibility for an interruption to occur in the electrical connection between the system’s power source and the HVAD controller, the FDA said in a statement on its website. The agency added, “Interruptions to the electrical connection could cause unintended intermittent electrical disconnection, which could result in a pump stop. A pump stop could cause patient harm such as exacerbation of heart failure symptoms, or symptoms such as mild weakness, dizziness, anxiety, nausea, loss of consciousness, or death.”
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