12 more patients dosed, Bluebird boosts strong profile for gene therapy

• Fresh data on Bluebird Bio’s Lenti-D reinforced the encouraging efficacy and safety profile the gene therapy demonstrated in the clinic last year, adding support to regulatory filings planned for 2019.
• Bluebird is testing Lenti-D in boys with a rare metabolic disorder called cerebral adrenoleukodystrophy, or CALD. Last year, early results from the Phase 2/3 STARBEAM trial showed 15 of 17 patients treated with the therapy were alive and free of major functional disabilities (MFDs) after two years. As of April 25, an additional 12 boys were given Lenti-D, none of whom experienced MFDs by a median follow-up of 4.2 months, the company said in a Wednesday statement.
• STARBEAM’s primary safety endpoint is the proportion of patients with grade 2 or higher acute graft-versus-host disease (GvHD) or chronic GvHD two years after treatment. None of the 29 patients on Lenti-D have experienced such diseases as of April 25, though there have been three adverse events potentially related to treatment with the therapy, including a grade 3 case of bladder inflammation caused by a virus.

Bluebird has a few busy years ahead. The Massachusetts-based biotech expects to file three therapies, including Lenti-D, for approval by the end of 2019. And by 2022, the aim is to have at least two products on the market.

In a Sept. 5 statement, Bluebird said it reached agreements with the Food and Drug Administration and the European Medicines Agency on regulatory pathways for Lenti-D. Meeting STARBEAM’s primary endpoints — MFD-free survival for efficacy, GvHD occurrence for safety — will be key to any approval decisions.

While proponents of gene therapy often tout it as an ultra-effective, one-time remedy for difficult-to-treat diseases, regulators have held some apprehension, particularly when it comes to safety. The FDA halted 27 gene therapy trials in 2003, for instance, after leukemia-like symptoms arose in two children enrolled in a gene therapy study. More recently, investors have been spooked by safety too. Spark Therapeutics lost around $1 billion in its market capitalization earlier this year as data on its hemophilia gene therapy raised some safety concerns.

“Even when there may be uncertainty about some questions, we need to make certain we assure patient safety and adequately characterize the potential risks and demonstrated benefits of these products,” FDA Commissioner Scott Gottlieb said in a July statement on new agency guidance for gene therapies.

To the point on safety, Bluebird is running an observational study that looks at outcomes of boys 17 and younger who have CALD and received allogeneic hematopoietic stem cell transplants (HSCTs). The biotech intends to compare data from that study with STARBEAM’s safety results.

In that study, 34% of the 41 patients who received allogeneic HSCTs experienced grade 2 or higher acute GvHD or chronic GvHD.

What’s more, it’s also conducting a long-term safety and efficacy follow-up study for STARBEAM participants treated with Lenti-D.

Bluebird said Lenti-D’s safety profile has so far been consistent with certain conditioning therapies used to suppress the immune system before allogeneic HSCTs.

“Data from the Phase 2/3 Starbeam study suggest that Lenti-D, which utilizes a child’s own cells and does not require a matched donor, may be a potential treatment for CALD,” Paul Gissen, a consultant in pediatric metabolic diseases at London’s Great Ormond Street Hospital and an investigator in the STARBEAM study, said in the Sept. 5 statement.

https://www.biopharmadive.com/news/with-12-more-patients-dosed-bluebird-reinforces-strong-profile-for-lenti-d/531635/

Chi-Med wins landmark cancer drug approval in China

• London-listed drugmaker Hutchinson China MediTech has won the first unconditional approval from Chinese regulators of a cancer medicine both discovered and developed in China, marking a milestone for the country’s emerging biotech sector.
• Better known as Chi-Med, the company on Wednesday said its drug, a VEGF inhibitor called fruquintinib, is now cleared to treat metastatic colorectal cancer in patients who have failed two other systemic therapies.
• Fruquintinib’s approval is a tangible sign of the progress made by a new crop of Chinese biotech companies that aim to invent novel therapies and shift away from the country’s historical role as a manufacturer of raw pharmaceutical ingredients.

Chi-Med began work on what would become fruquintinib in 2007, pushing the compound into clinical testing four years later. That decade-plus of drug development has now paid off, with an approval that puts the drugmaker at the forefront of China’s biotech scene.

Clinical progress from biotechs like Chi-Med, coupled with sweeping regulatory reforms and the recent opening of Hong Kong’s stock exchange to pre-revenue biotech companies, has fueled a surge of interest in Chinese drug development.

Historically, China’s contribution to drug supply chains has been the active pharmaceutical ingredients that make up foreign-made medicines. Chi-Med and its Chinese biotech peers, on the other hand, hope to take their place alongside U.S. and European companies in developing new drugs.

It’s clear why drugmakers are interested in introducing more branded drugs in China. The country is the second-largest market for drugs globally, trailing only the U.S. in overall size.

Fruquintinib’s approval was backed up by a Phase 3 study, published in JAMA earlier this year, that showed the drug improved median overall survival versus placebo by nearly three months in 416 colorectal cancer patients whose tumors had grown after prior treatment with two chemotherapies.

The National Medical Products Administration of China approved fruquintinib roughly a year after granting the drug priority review status.

“What that illustrates is that Chinese companies now are conducting science and developing drugs in a way that meets the height of global standards,” said Brad Loncar, head of Loncar Investments, in an interview with BioPharma Dive. “I think that this is a sign of things to come.”

That optimism is tempered, however, by continued concerns over production quality among Chinese manufacturers. A recent vaccine scandal and global recalls of a heart drug made by a Chinese drugmaker indicate that, even as biotech companies push forward, the broader industry still lags in meeting global standards.

Under a 2013 collaboration deal with Chi-Med, Eli Lilly will launch fruquintinib in China under the brand name Elunate.

Studies of the drug in gastric and lung cancer are ongoing and, in December of last year, Chi-Med initiated a Phase 1 trial in the U.S.

Beyond fruquintinib, Chi-Med hopes to win approval of two other cancer drugs within the next three years.

Other Chinese biotechs are making strides in drug development as well. Beigene recently filed for Chinese approval of its anti-PD-1 cancer immunotherapy tislelizumab and Jiangsu Hengrui Medicine won a conditional approval for its breast cancer drug pyrotinib.

At the same time, Chinese regulators have ramped up the pace of approvals of foreign-made drugs, particularly in cancer. Just in the past few months, Merck & Co., Bristol-Myers Squibb, Roche and AstraZeneca have all secured OKs for key drugs, including the immuno-oncology stars Opdivo (nivolumab) and Keytruda (pembrolizumab).

https://www.biopharmadive.com/news/chi-med-wins-landmark-china-approval-cancer-drug-fruquintinib/531612/

More Bad News About Benzos

Hello. I’m Dr Arefa Cassoobhoy, a practicing internist, Medscape advisor, and senior medical director for WebMD. Welcome to Medscape Morning Report, our 1-minute news story for primary care.

Benzodiazepines are in the news again—this time, not for the increased risk for falls and fractures that can come with their use.

A case-control study was conducted in Finland among community-dwelling adults who had been diagnosed with Alzheimer disease. Benzodiazepines and related Z drug use was associated with a modestly increased risk for Alzheimer disease. No real differences were seen for the drug subcategories. This included short-, medium-, and long-acting benzodiazepines, as well as zolpidem, zaleplon, and eszopiclone.

The analysis showed that 5.7% of dementia cases among adults using benzodiazepines were due to the drugs. Even this small increased risk could be significant because they are widely prescribed to elderly adults, often long term. The drugs are given to treat prodromal and neuropsychiatric symptoms of dementia like insomnia and anxiety.

The authors concluded that benzodiazepines and Z drugs should be avoided when possible, given their adverse-event profile. For patients who you would like to wean off benzodiazepines, deprescribing can be tough and take a long time. Guidelines are now available to help you with the process.

https://www.medscape.com/viewarticle/901271

Bovie Medical initiated at Piper Jaffray

Bovie Medical resumed with an Overweight at Piper Jaffray. Piper Jaffray analyst Matt O’Brien resumed Bovie Medical with an Overweight rating and a price target of $8 after the company’s business update call today regarding the completed divestiture of its core franchise, saying the company now intends to invest the proceeds in its J-Plasma sales channel. O’Brien notes that this is a “correct” strategic decision in spite of the uncertainty regarding the company’s financials in the coming quarters, adding that revenue growth will likely be “considerable” in 2019 and 2020. The analyst recommends that risk-tolerant investors begin to accumulate positions in the stock.

https://thefly.com/landingPageNews.php?id=2786277

Embattled blood-testing firm Theranos to dissolve

Theranos Inc, the once-celebrated Silicon Valley blood-testing firm, is about to dissolve itself months after top executives were indicted for defrauding investors, the Wall Street Journal reported on Wednesday.

The move follows a failed attempt by Theranos to sell itself, during which it reached out to more than 80 potential buyers through Jefferies Group, the Journal reported, citing an email to shareholders from Chief Executive David Taylor.

“Unfortunately, none of those leads has materialized into a transaction. We are now out of time,” Taylor wrote in the letter, a copy of which was published by the WSJ.

The firm will attempt to pay unsecured creditors its remaining cash in the coming months, the Journal reported, adding that big name investors had lost about $1 billion.

Neither Taylor nor representatives for Palo Alto, California-based Theranos immediately responded to Reuters’ requests for comment.

Theranos founder Elizabeth Holmes, who started the company when she was 19, was celebrated as a rising Silicon Valley star until it became clear that many of the claims about the company’s supposedly revolutionary blood test were bogus.

In June this year, Holmes and former Theranos president Ramesh “Sunny” Balwani were indicted on charges that they engaged in schemes to defraud investors, doctors and patients.

They used advertising and solicitations to encourage doctors and patients to use Theranos’s blood testing laboratory services despite knowing the company could not produce accurate and reliable results consistently, prosecutors had said.

Theranos was in default under its credit facility with Fortress Investment Group, Taylor said in the letter.

He said the company was attempting to reach an agreement with Fortress to give it ownership of Theranos’ patents but leaving its remaining cash of about $5 million for distribution to other unsecured creditors.

Besides Fortress, Theranos owes at least $60 million to unsecured creditors, Taylor said. “Because the company’s cash is not nearly sufficient to pay all of its creditors in full, there will be no distributions to shareholders,” he added.

The company aims to seek board and shareholder consent for the Fortress settlement and corporate dissolution later this week and proceed with the actions starting Monday, Taylor said.

https://www.reuters.com/article/us-theranos-bankruptcy/embattled-blood-testing-firm-theranos-to-dissolve-wsj-idUSKCN1LL077

Westlake Bio Unveils $320M Fund to Put Los Angeles on the Biotech Map

Los Angeles has long been in San Francisco’s shadow when it comes to life sciences investment. But a new venture capital firm led by industry veterans is trying to cast the City of Angels in a new light.

Westlake Village BioPartners is launching today with $320 million in committed capital. The Los Angeles-based firm is led by managing directors Beth Seidenberg, a former general partner at venture capital firm Kleiner Perkins, and Sean Harper, the outgoing executive vice president of research and development at Amgen (NASDAQ: AMGN). Harper will start with Westlake in January after retiring from Amgen. Scott Ryles, chief operating officer of Kleiner Perkins, is joining Westlake as its COO.

Seidenberg shares Amgen ties with Harper. Before joining Menlo Park, CA-based Kleiner Perkins in 2005, she was Amgen’s chief medical officer. Kleiner Perkins invests in both technology and life sciences, and although there is growing overlap between the two fields, Seidenberg says she’ll have more opportunities at Westlake.

“At Kleiner Perkins, the amount of capital I would have to focus on life sciences was less than what I thought a dedicated life sciences fund would be able to have,” she says.

Westlake will invest primarily in pharmaceutical and biotech companies, but the firm will be open to other technologies with medical applications, says Seidenberg. Most investments will be in early-stage startups. Seidenberg adds that Westlake will incubate some technologies with seed money before committing to a full Series A round of financing. Westlake has already started talking with entrepreneurs, though Seidenberg declined to discuss additional details such as the therapeutic areas of potential investments.

The Los Angeles area attracts a fair amount of venture capital—it was the nation’s fifth largest market from 2006 to 2016, according to Pitchbook—but most of the investment is in is in high tech.

Harper says Westlake can play a role in boosting the L.A. life sciences sector. UCLA and CalTech are already churning out biotech innovations, and large pharmaceutical companies such as Thousand Oaks, CA-based Amgen and Allergan (NYSE: AGN), which has a large presence in Irvine, CA, have helped broaden the pool of life science workers throughout the region.

“The thing that’s really been missing in terms of sparking a really vibrant ecosystem like you see in Boston and San Francisco is having a dedicated life sciences venture group that knows what it’s doing from a scientific and technical perspective,” Harper says.

Harper has lived in Southern California for 16 years. For Seidenberg, Westlake represents a homecoming, though she points out that she never really left. For the past 13 years, she’s been commuting to the Bay Area from her L.A. home. She says that many of the L.A.-area biotech entrepreneurs are like her: industry veterans who are returning to Southern California from other parts of the country to try something new.

“This is the golden age of biotech,” Seidenberg says. “The opportunities for biotech investing, having been in this industry for nearly 30 years, are better than I’ve ever seen.”

https://www.xconomy.com/national/2018/09/05/westlake-bio-unveils-320m-fund-to-put-los-angeles-on-the-biotech-map/

FDA OKs Loxo in 2nd ‘breakthrough’ in tissue-agnostic cancer therapy

Three months ago at ASCO, Loxo Oncology wowed the crowd at the big cancer conference with some early-stage data for its second genetically targeted cancer drug candidate. Today, the biotech announced that the FDA seems similarly impressed, offering a breakthrough drug designation to shorten the regulatory timeline just as Loxo has hoped.

In the interim Phase I/II snapshot provided at ASCO, LOXO-292 spurred a 77% overall response rate for RET fusion-positive cases, the majority of which belonged to the non-small cell lung cancer. In RET-mutant medullary thyroid cancer the rate dropped to 45%.
Correspondingly, the BTD was granted for the treatment of two types of patients, both heavily pretreated: those with metastatic RET-fusion-positive non-small cell lung cancer who require systemic therapy and have progressed following chemo and checkpoint therapies; and those with RET-mutant medullary thyroid cancer needing systemic therapy who have progressed following prior treatment without any alternatives.

Stamford, CT-based Loxo $LOXO is one of the trailblazers in personalized cancer therapies, where patients are grouped no by the site of tumor development but by genetics — an approach that calls for broader sequencing to ID the genetic mutations underpinning each patients’ cancer.

Following a game plan that has catapulted larotrectinib to the final run-up of a widely expected approval in November, Loxo says it will design the next steps in clinical development based on feedback from regulators worldwide — with the final plan expected in 2019.

“We look forward to working with FDA to streamline the development of LOXO-292 in the two patient populations that have comprised the bulk of our initial clinical trial enrollment,” said Josh Bilenker. “Given the many available therapies for non-small cell lung cancer and medullary thyroid cancer, we are pleased that LOXO-292 has shown encouraging data in refractory patients, and hope to demonstrate the full potential of this treatment in additional populations over time.”

https://endpts.com/fda-waves-loxo-through-for-second-breakthrough-in-tissue-agnostic-cancer-therapy/