Our proprietary gene therapy candidate, AVXS-101, is in human clinical trials for the treatment of spinal muscular atrophy (SMA) Type 1. SMA is a severe neuromuscular disease caused by a genetic defect in the SMN1 (survival motor neuron 1) gene, leading to the loss of motor neurons and resulting in progressive muscle weakness and paralysis.
The AVXS-101 Design We’ve developed AVXS-101 to possess four key elements of an optimal gene therapy approach to SMA. 1) Recombinant AAV9 Capsid Shell is a non-replicating adeno-associated virus capsid used to deliver a functional copy of the human SMN gene across the blood-brain barrier to cells without modifying the patient’s existing DNA 2) Human SMN Transgene is a stable, functioning SMN gene that is introduced into the cell’s nucleus 3) scAAV ITR (Self-complementary DNA Technology) is a human SMN transgene introduced as a self-complementary double- stranded molecule. The inclusion of this technology enables rapid onset of effect 4) Continuous Promoter activates the transgene and is designed to allow for continuous and sustained SMN expression
ESSENTIAL FACTS ABOUT SMA Spinal muscular atrophy (SMA) is a genetic neuromuscular disease. Here are some quick SMA stats:
1) It's the number 1 genetic cause of infant death 2) As many as 1 in 10,000 live births may be affected 3) 6,000,000 people or 1 in 50 americans are genetic carriers 4) SMA can affect people of any race or gender 5) There is NO approved treatment (survivors require lifelong care and support)
Jefferies analyst Biren Amin reiterated a Buy rating and boosted his price target on AveXis (NASDAQ: AVXS) to $50.00 (from $42.00) after they found a patient we believe is in the AVXS-101 trial whose parents posted a video of her walking.
While the firm does not have 100% confirmation that this patient is indeed in the AVXS trial, they think there's a strong likelihood that she is in the AVXS-101 trial.
"We believe her achievement to walk is significant given that she a Type 1 SMA baby w/ 2 copy number and would not in any normal circumstance be expected to walk (walking seen in Type 3 SMA). Our finding comes ahead of AVXS' plan to disclose patient data on motor milestones from its PI trial later this year."
Post by Gene Editing on Sept 20, 2016 2:25:10 GMT -6
Jefferies a baby is walking
We have found a patient we believe is in the AVXS-101 trial whose parents posted a video of her walking. We believe her achievement to walk is significant given that she a Type 1 SMA baby w/ 2 copy number and would not in any normal circumstance be expected to walk (walking seen in Type 3 SMA). Our finding comes ahead of AVXS' plan to disclose patient data on motor milestones from its PI trial later this year. What We Know About This Walker: We first would state that we do not have 100% confirmation that this patient is indeed in the AVXS trial; however we think there's a strong likelihood that she is in the AVXS-101 trial. We will withhold from publishing the patient's name outright for patient/family sensitivity. She is approximately 20 months old and has shown motor function improvement as seen in photographs posted on social media for the last ~12 months. At ~8 months of age, she is able to slightly scoot along the floor laying on the stomach and unable to rollover onto her back. At 16 months of age, she has the ability to sit unaided and stand with support. At 19 months old, we see her able to walk unaided, take 15+ steps twice in a row with no break. In addition, the mother provides a link to the AVXS-101 trial and states "here is the update on gene therapy by our Doc and one of the families from the trial". We Match Patient to AVXS-101 Data: AVXS has provided quarterly updates of the PI trial of AVXS-101 in SMA Type 1. Based on the CHOP INTEND scores for each patient in the AVXS-101 trial, the profile of the patient in the video lines up quite well with patient E.06 in the high dose cohort who we have seen improve CHOP INTEND scores to a perfect score (64) and maintained that score for >6 months. As of July 1, 2016, this patient is slightly less than 18 months old, which matches the current age of the patient seen on social media, which reports 20 months of age. The pt was treated at 2 mos, which suggests she was either a Type Ia or Ib pt. Increased Confidence in AVXS-101: We view this data of at least one patient walking and the matching up with the profile of a patient seen in the AVXS-101 reported data as additional evidence of AVXS-101's effect. With this additional anecdotal evidence, we are more confident in AVXS-101's prospects and lower our risk discount to 30% from our previous 40% estimate and increase our PT to $50 from $42. Valuation/Risks Our $50 PT vs prev $42 is DCF based. Risks include clinical, regulatory, and commercial.
Valuation We raise our PT to $50 from $42 based on the likely confirmation of strong efficacy and de-risking of AVXS-101 in SMA Type 1. This comes from evidence on social media of a patient we believe to be in the AVXS-101 trial walking unaided. We use a DCF valuation model, which assumes a WACC of 14% and outstanding shares of 27.4 million, driven by our risk-adjusted AVXS-101 worldwide peak sales of $526M in 2025. AveXis management continues to expect to provide quarterly updates on the progress of the ongoing PI clinical trial. Full data set from all 15 patients in the PI is expected in 1Q17 and would drive the start of pivotal trials in both the EU and US in 1H17. AveXis also plans to explore the use of AVXS-101 in SMA Type II, and a trial in this population is expected to initiate in 2H16 utilizing intrathecal administration of AVXS-101. We currently do not provide any value for Type 2 and 3 SMA opportunity as there has been no clinical data generated. We assume a significant increase in R&D expenses in 2016 as AveXis initiates the trial in SMA Type II and continues investing in the ongoing PI in SMA Type I. We assume an R&D expense trend for 2016-2020 to be $50-70 million. We estimate SG&A expense will increase to $35M in 2020 to support the launch of AVXS-101. Exhibit 1: DCF sensitivity analysis Source: Jefferies estimates Risks Clinical Failure: As with all companies in biotechnology and pharmaceuticals developing treatments of the future, a clinical failure can lead to delays in approval or possibly discontinuation of programs. AveXis relies on the success of AVXS-101 for SMA, currently the only product in the pipeline. Regulatory Failure: The FDA could determine the data produced by AveXis is inadequate and could delay approval. Any delays in approval timelines could impact our earnings estimates, price target, and/or rating. Commercial Failure: We currently project $270 million (risk-adjusted) in U.S. sales for AVXS-101 in 2030. Our estimates may rely on the success of the company/partners to receive drug reimbursement from private/public payers. Financing Risks: We expect AveXis to have adequate cash through commercialization of AVXS-101. However if additional trials or drugs are tested AveXis and may need additional financing(s) to fund its R&D programs and a sales and marketing infrastructure. The company could partner AVXS-101 ex-U.S. licensing rights; however, we currently do not assume this as our base case.
Novartis Launches CRISPR Collaborations with Intellia, Caribou Alex Philippidis Novartis said today it is launching collaborations with a pair of partners that will enable it to use CRISPR genome editing technology to discover and develop new medicines. The value of both collaborations was undisclosed.
The pharma giant will team up with Intellia Therapeutics to explore options for using CRISPR to engineer chimeric antigen receptor (CAR) T cells and hematopoietic stem cells.
Both potential uses tie in with Novartis R&D priorities that the company has sought to advance in recent months.
In October, Novartis disclosed preliminary study results showing that 27 of 30 pediatric and adult patients with relapsed/refractory acute lymphoblastic leukemia (90%) experienced complete remissions with CTL019, a personalized cellular immunotherapy being co-developed by the company with the University of Pennsylvania under an exclusive global research and licensing agreement signed in 2012.
And in August, Novartis signaled again its interest in stem cell medicine by investing $35 million to take a 15% stake in Gamida Cell, developer of the investigational stem cell therapy NiCord.® The experimental drug—now in Phase I/II trials for hematological malignancies such as leukemia and lymphoma—received orphan drug designations by both the FDA and the European Medicines Agency, the company said yesterday.
Novartis has an option to fully acquire Gamida Cell for $165 million. But that option is only available for an undisclosed limited time, and tied to achieving unspecified milestones related to the development of NiCord —milestones that Gamida Cell has said it anticipates being met this year. The deal came less than a year after the September 2013 launch of Novartis’ collaboration with Regenerex allowing the pharma to use the latter’s hematopoietic stem cell-based Facilitating Cell Therapy (FCRx) platform, which has been investigated in kidney transplantation.
Under its collaboration with Intellia, Novartis will receive exclusive rights to develop all collaboration programs focused on engineered CAR Ts, as well as the right to develop an undisclosed number of targets for ex vivo editing of HSCs. In addition, Novartis is receiving nonexclusive rights for limited in vivo therapeutic applications of CRISPR systems.
Novartis also agreed to increase an equity investment made earlier in Intellia through an upfront payment of undisclosed amount, and consented as well to provide technology access fees and funding for R&D programs during the five-year term of the collaboration. Intellia could also receive downstream payments tied to successfully achieving milestones, as well as royalties.
Intellia’s launch was announced November 18. The startup received an undisclosed amount of financing from Novartis, as well as $15 million each from Atlas Venture and Caribou Biosciences, in a Series A financing round.
Caribou is the second company with which Novartis is launching a CRISPR-related collaboration. The pharma giant said it plans to use Caribou’s foundational CRISPR platform and intellectual property as a research tool for drug discovery. Novartis is receiving nonexclusive rights to Caribou's CRISPR platform for research conducted during the collaboration, and has agreed to fund the companies’ one-year research program. Novartis is also making a series A equity investment of undisclosed amount in the company.
Caribou's CRISPR technology is based on research by the laboratory of Jennifer Doudna, Ph.D., of the University of California, Berkeley, and collaborators. Caribou'sCRISPR technologies IP portfolio is centered on an exclusive license to the foundational CRISPR-Cas9 work from the University of California and the University of Vienna.
The Novartis-Caribou partnership is designed to draw upon Intellia's CRISPR expertise as well as Novartis’ expertise in research and in cell and gene therapy development at the Novartis Institutes for BioMedical Research (NIBR).
“We have glimpsed the power of CRISPR tools in our scientific programs in NIBR, and it is now time to explore how to safely extend this powerful technology to the clinic,” NIBR President Mark Fishman said in a statement. “Much remains to be learned, and we are delighted to explore these directions with colleagues from Intellia and Caribou.”
Novartis gene therapy approval signals new cancer treatment era Bill Berkrot
(Reuters) - Novartis AG on Wednesday won highly anticipated U.S. approval for the first of a new type of potent gene-modifying immunotherapy for leukemia, a $475,000 treatment that marks the start of a potential new treatment paradigm for some cancers.
The approval was widely expected after an FDA advisory panel last month unanimously recommended the action.
Novartis shares closed virtually unchanged in Swiss trading.
Novartis also announced an agreement with the U.S. Centers for Medicare and Medicaid Services under which payment for the therapy will be based on clinical outcomes achieved.
The treatment, called Kymriah, was approved for patients up to 25 years of age who have relapsed or not helped by prior treatment for B-cell acute lymphoblastic leukemia (ALL).
Dr Kevin Curran, a pediatric oncologist at Memorial Sloan Kettering Cancer Center in New York, noted the treatment’s high cost.
“Of course, we have to talk about pricing from a national standpoint,” he said. “But if I have a parent and a (sick) child in front of me, and I have an opportunity to save them, we’re going to take that.”
Kymriah belongs to a new class of treatments called CAR-T therapies. It involves removing disease-fighting T cells from a patient, genetically modifying them to better recognize and attack cancer, and then replacing them, where they can circulate for years seeking out the disease.
Novartis estimates some 600 ALL patients a year would be eligible for Kymriah. It expects to open five treatment centers within days and 35 by year-end.
”We’re entering a new frontier in medical innovation with the ability to reprogram a patient’s own cells to attack a deadly cancer,” Food and Drug Administration Commissioner Scott Gottlieb said in a statement.
The FDA said it has granted 76 applications for trials involving experimental CAR-T therapies.
Shares of Gilead Sciences Inc, which this week announced an $11.9 billion deal to buy Kite Pharma, were up 6.2 percent to $80.47 on Wednesday afternoon, as Kite is widely expected to receive the next U.S. approval of a CAR-T therapy for a different blood cancer.
Shares of Bluebird Bio Inc, which is developing a promising CAR-T treatment, were up 11.1 percent at $113.73.
“Two years ago many people would have told you these types of treatments were science fiction,” said Brad Loncar, chief executive of Loncar Investments, which runs the Loncar Cancer Immunotherapy ETF
In clinical trials, CAR-T therapies have shown remarkable efficacy against blood cancers. In the pivotal Novartis trial, 83 percent of patients achieved remission with a disease that has historically poor outcomes.
“We’ve never seen anything like this before and I believe this therapy may become the new standard of care for this patient population,” Dr Stephan Grupp of Children’s Hospital of Philadelphia said in a statement.
However, this type of therapy carries risk of severe side effects. Kymriah will have a boxed warning for cytokine release syndrome, a potentially lethal systemic response to the activation and proliferation of CAR-T cells, causing high fever and potential for neurological problems.
Shares of Juno Therapeutics Inc, which last year reported a handful of patient deaths during trials of its CAR-T therapy, were down 8.9 percent at $39.92.
Reporting by Bill Berkrot and Mike Erman in New York, Natalie Grover in Bengaluru, Deena Beasley in Los Angeles and Julie Steenhuysen in Chicago; Editing by Shounak Dasgupta and Matthew Lewis
Why Celgene's Acquisition Of Juno Matters For Biotech And Investors Steve Brozak , CONTRIBUTOR
Opinions expressed by Forbes Contributors are their own. Celgene’s acquisition of Juno is probably the most anticipated acquisition of the last 24 months. Having previously made a $1 billion investment a little over two years ago, Celgene completed its courtship of the company yesterday in a $9 billion takeover. But the path to acquisition wasn’t straightforward (nothing really ever is when you’re dealing with biotech), and there was some doubt when Juno’s lead program, JCAR14, stumbled in the clinic, putting the company two years behind its competition, and casting a shadow over its next lead therapy, JCAR17.
A few years ago the rise of CAR-T technology was being whispered about in biotech circles as a potential Celgene killer. The biotech bellwether’s franchise had solidly dominated the blood cancer space as a near hegemon, but the rise of CAR-T and other immunotherapies over the last seven years threatened to shift entirely the way hematology and oncology are practiced. Meanwhile, Novartis and Gilead jumped feet first into the CAR-T space.
In 2012 Novartis entered into an alliance with the University of Pennsylvania, which included a $20 million investment by the pharmaceutical company. The Novartis-Penn Center for Advanced Cellular Therapeutics opened up four years later in 2016, and this past August, Novartis received the first FDA approval for a CAR-T cell therapy called Kymriah for pediatric B-cell acute lymphoblastic leukemia (ALL). The Novartis-Penn team-up was a landmark event in science and medicine which shouldn’t be overlooked for its significance. Novartis was the first major pharmaceutical company to fully enter CAR-T therapy arena, accelerating investment and development in the field, taking a build-it-and-they-will-come approach to big pharma concerns around an incredibly risky therapeutic approach with complicated manufacturing and product delivery process.
Compare Novartis’ transition to Bristol Myers Squibb, once considered the leader in immunotherapy, which has entangled itself in an attempt to use its successful checkpoint inhibitor programs to pivot the entire company into a “biopharma” company. The pivot is a business restructuring/re-branding process Bristol Myers Squibb kicked off 10 years ago with the fanfare of a new drug approval. Bristol Myers Squibb has also been locked in a duel with Merck with its checkpoint inhibitors, meanwhile Bristol’s once vaunted business development strategy of externally investing in smaller biotechs it referred to as its “string-of-pearls” has been crushed to dust. It should have been a company like BMS that entered full on in the immunotherapy realm.
Novartis’ unlikely entry and then approval must have sent the alarm bells ringing at Celgene. But it wasn’t until Gilead, one of biotech’s fiercest competitors, acquired Kite Pharmaceuticals, another CAR-T company, that Celgene was forced to protect its own position in the space and fully acquire Juno. Gilead acquired Kite Pharma in August 2017 and received approval for its CAR-T product, Yescarta, in October 2017.
PHILADELPHIA — In an alliance aimed at bringing a new, personalized immunotherapy approach to patients with a wide variety of cancers, the University of Pennsylvania and Novartis announced today an exclusive global research and licensing agreement to further study and commercialize novel cellular immunotherapies using chimeric antigen receptor (CAR) technologies. The agreement, which follows a Penn research team's 2011 publication of breakthrough results in several chronic lymphocytic leukemia patients treated with this personalized immunotherapy technique, paves the way for pivotal studies that have the potential to expand the use of CAR therapies for additional cancers.
The new alliance represents a marquee achievement in Penn's commitment to translational science aimed at expediting the process of bringing novel therapies to patients. Together, Penn and Novartis will build a first-of-its-kind Center for Advanced Cellular Therapies (CACT) on the Penn campus in Philadelphia -- a venture which will bring full circle the 1960 discovery of the Philadelphia chromosome, the first description of a chromosome abnormality that causes cancer. The center will be devoted to the discovery, development and manufacturing of adoptive T cell immunotherapies through a joint research and development program led by scientists and clinicians from Penn, Novartis, and the Novartis Institutes for Biomedical Research.
"Penn's intellectual resources, combined with a pharmaceutical industry leader like Novartis, offer a powerful symbiotic relationship in our mutual goal of finding more effective treatments for cancer," said J. Larry Jameson, MD, PhD, dean of the Perelman School of the Medicine at the University of Pennsylvania and executive vice president for the Health System. "With our shared commitment to rapidly advancing new therapies and cures, this new alliance will provide the support for the essential clinical trials with engineered T cells, which could open doors for use of promising treatment options for many cancer patients who have reached the end of currently available treatments."
Under the terms of the agreement, Penn grants Novartis an exclusive worldwide license to the technologies used in an ongoing trial of patients with chronic lymphocytic leukemia (CLL) as well as future CAR-based therapies developed through the collaboration. Novartis will invest in the establishment of the CACT and future research of the technology. Additional milestone and royalty payments to Penn are also part of the agreement.
In August 2011, the Penn team detailed the results of an early trial utilizing the modified T cell approach among a small group of advanced chronic lymphocytic leukemia patients in the New England Journal of Medicine and Science Translational Medicine. The findings — including reports on two patients who remained in remission more than a year after their treatment — served as the first successful and sustained demonstration of the use of gene transfer therapy to create T cells aimed at battling cancerous tumors. The protocol involves removing a patient's cells and modifying them in Penn's cell and vaccine production facility, then infusing the new cells back into the patient's body following chemotherapy to attack their remaining tumors. Thus far, the study has involved only patients whose cancers have not responded to traditional therapy. These patients' only remaining treatment options would have been a bone marrow transplant, a procedure which carries a mortality risk of at least 20 percent.
"Our early results in patients treated with chimeric antigen receptors represent two decades of investment and perseverance in our effort to treat cancer in an entirely new way, combining a highly targeted cell-based therapy with the might of a patient's own immune system," said the study's leader, Carl June, MD, a professor of Pathology and Laboratory Medicine in the Perelman School of Medicine and director of Translational Research at Penn's Abramson Cancer Center. "By joining forces with Novartis, we will now have the resources and space to expand our research in new directions that we hope will change the way cancers of all kinds are treated."
Although further studies are needed to explore the long-term viability of the treatment, June's team showed that in the patients studied so far, months after infusion, the new cells had multiplied throughout the patients' bodies and were capable of continuing their "seek-and-destroy" mission against cancerous cells.
In addition to continued trials in CLL, Penn also has engineered T cell trials underway for other leukemias as well as lymphoma, mesothelioma, myeloma, and neuroblastoma. To read more about the early results of Penn's work using the new treatment approach and watch a video of June and his co-investigators discussing the research, visit Penn Medicine's online press kit.
Spark Therapeutics Enters into a Licensing and Supply Agreement for Investigational Voretigene Neparvovec Outside the U.S. Novartis Pharmaceuticals will commercialize investigational voretigene neparvovecwhen and if approvedin Europe and all other markets outside the U.S.; Spark Therapeutics retains U.S. commercial rights for LUXTURNA™ (voretigene neparvovec-ryzl)
Agreement leverages Novartis’ extensive ex-US ophthalmology capabilities and infrastructure to the benefit of patients outside of U.S.
Spark Therapeutics to receive $105 million as an upfront fee and is eligible to receive up to $65 million in milestone payments, as well as receive a royalty on net sales outside the U.S.
PHILADELPHIA, Jan. 24, 2018 (GLOBE NEWSWIRE) -- Spark Therapeutics (NASDAQ:ONCE), a fully integrated gene therapy company dedicated to challenging the inevitability of genetic disease, today announced it has entered into a licensing agreement with Novartis Pharmaceuticals to develop and commercialize investigational voretigene neparvovec outside the U.S., while Spark Therapeutics will continue to exclusively commercialize LUXTURNA™ (voretigene neparvovec-ryzl) in the U.S. Under the agreement, Spark Therapeutics will retain regulatory responsibility for obtaining European Medicines Agency approval for investigational voretigene neparvovec. Spark Therapeutics also entered into a separate agreement to manufacture and supply investigational voretigene neparvovec to Novartis. No other programs in Spark Therapeutics’ pipeline are part of this agreement.
Under the terms of the licensing agreement, Novartis will pay Spark Therapeutics$105 million in cash as an upfront fee. Spark Therapeutics is eligible to receive up to an additional $65 million in cash milestone payments based on near-term European Regulatory Agency (EMA) regulatory approval and initial sales outside the U.S. in certain markets. Spark Therapeutics is also entitled to receive royalty payments on net sales of investigational voretigene neparvovec outside the U.S.
“By leveraging Novartis’ large, existing commercial and medical infrastructure in ophthalmology, as well as its commitment to commercializing genetic-based medicines, we help ensure that more patients with confirmed biallelic RPE65 mutation-associated retinal dystrophy who live outside the U.S., and importantly outside of Europe, have access to investigational voretigene neparvovec,” said Dan Faga, chief business officer, Spark Therapeutics. “We intend to use the proceeds from this transaction to continue to develop our robust pipeline of investigational gene therapies to create a path to a world where no life is limited by genetic disease.”
The Pharma Exec behind the First Approved Gene Therapy Is Hunting for His Next Big Break Novartis’s retiring CEO hopes such treatments will soon be deployed against lymphoma, other cancers
By Karen Weintraub on January 25, 2018 The Pharma Exec behind the First Approved Gene Therapy Is Hunting for His Next Big Break
Joseph Jimenez retires at the end of the month after eight years in the top job at Novartis, one of the world’s largest pharmaceutical companies. Under his leadership the company sold off its vaccine division and shifted its focus to developing generic drugs as well as products for treating retinal diseases, glaucoma and dry eye, among other conditions. But his tenure will be remembered largely for putting gene therapies on the map.
Last year Novartis became the first company to get approval from the U.S. Food and Drug Administration for this type of treatment. The company’s CAR-T (short for chimeric antigen receptor T cells) therapy is a type of personalized medicine in which a patient’s own immune cells are removed, reengineered to target and kill cancer cells and infused back into the body. Marketed under the name Kymriah, this therapy is currently only approved to treat children and young adults with acute lymphoblastic leukemia, but the company expects it will eventually be approved for other cancers.
The catch, of course, is the price tag. Kymriah, developed in collaboration with researchers at the University of Pennsylvania under the name CTL019, is a one-time infusion that costs $475,000 per person. In an unusual move designed to counter complaints about unaffordability, Jimenez has promised Novartis will only charge for Kymriah if a patient sees a positive response within the first 30 days. (Studies show the treatment triggers a complete remission in more than 80 percent of patients, who typically start to see results within a few days.) Some patients relapse in the long term, or develop serious side effects—including an immune system overreaction that leads to intense flulike symptoms. Yet the extraordinarily high response rate puts Kymriah in the very small category of truly transformative treatments.
Scientific American spoke with Jimenez about CAR-T therapy, his hopes for new game-changing treatments that could target disease-causing proteins and problems with the U.S. health care system.
Do you think CAR-T immune therapies like Kymriah may ever be useful beyond blood cancers? We have mixed views at the company about that. Some [of us] believe that we will find a way to impact solid tumors, particularly in combination with other drugs. Right now we’re very confident in the technology for different blood cancers but we’re still in the proof-of-concept stages for solid tumors.
What made you pursue CAR-T, even as other large pharmaceutical companies decided not to bet on the technology? Novartis was known for breakthrough innovations in oncology back in the early 2000s. We developed Gleevec [which treats certain types of blood and intestinal cancers with less collateral damage to healthy cells than a typical chemotherapy]. When we saw the data on CTL019 CAR-T coming out of Penn—the really early data about five years ago—we decided that this was a place where we were going to place a big bet. The data reminded us of the early days of Gleevec, and so we went out on a limb.
Why is Novartis able to invest in such a long-term gamble while other companies aren’t? We’re a Swiss company, which makes us a little bit more insulated from the quarter-to-quarter pressures that some of the other pharmaceutical companies feel. We have a longer-term view and we have an investor base that is perhaps more patient than some others, so that gives us the ability to invest for the long term.
Is there another gamble like that in the works now? There’s a new technology that Jay Bradner, the head of our research organization, is championing: protein degradation [essentially tricking the body into disposing of harmful proteins], which is a new approach to addressing intractable [disease] targets. We’re also investing heavily in gene editing because we do believe there will be therapeutic value coming out of gene editing.
How confident are you that CRISPR will be usable to edit genes in sick people? So far it’s promising, but I think everybody is in a wait-and-see mode. There will be twists and turns along the path, as there is with any new technology.
After more than a decade working for a European drug company, have you come up with any ideas for fixing America’s health care system? Obviously, the current system is not sustainable. I really believe that the only way it’s going to shift is if we shift away from this transactional approach of selling pills or fee-for-service towards an outcomes-based one, where we get paid for the results that we deliver. If you were to say, “We’re only going to get paid based on the outcome we deliver,” you could eliminate a lot of the waste in the system.
Do you have a solution for the high cost of drugs? A pharmaceutical company gets 60 percent of the dollar that is paid for the drug. Forty percent goes to the supply chain: the pharmacy benefit manager, the wholesaler, the retailer. That seems wrong. We’re the ones taking all the risk. We’re the ones developing the drug. That 40 percent—how do we find a way to get [some of] that money into the hands of the patient at the pharmacy benefit counter? If we can do that, we can put a serious dent in pharma costs in the U.S.
So, you’re saying drug costs could come down by cutting the money made by insurance companies and retailers? How do you make that happen? Most Medicare patients are on fixed incomes, and when they go to the pharmacy counter they’re not able to get any kind of co-pay assistance. One way we could help these seniors that are seeing big increases in either deductibles or co-pays is to help them with that out-of-pocket expense. There is a legislative and regulatory approach that we’re working on to try to effect that.
What’s next for you? Will you be starting a company, or joining one? I haven’t decided if I want to do a portfolio of companies and be on the investing side—helping these companies get formed and started—or whether I want to enter an early-stage company and actually operate it.
AveXis steps up gene therapy pursuit of Biogen’s SMA pathfinder by Phil Taylor | Jan 16, 2018 9:35am
New trials expand the program into different SMA populations, and to Europe. is expanding trials of its gene therapy for children with spinal muscular atrophy (SMA) with a series of new trials as it plays catch-up with Biogen and Ionis, which claimed the first approval for an SMA drug.
The Chicago biotech already has pivotal trials of its AVXS-101 candidate underway in two variants of the severe neuromuscular disease—types 1 and 2—but says it will now start studies in patients with SMA type 3, older children with type 2, and very young children (less than six weeks old) who have yet to develop symptoms.
It’s also got an eye on the European development of the gene therapy, with a new SMA type 1 study that it hopes will support approval by the EMA.
Biogen and Ionis’ Spinraza (nusinersen) was approved by the FDA near the end of 2016 and is still the only drug approved to treat SMA, which can affect up to 10,000 children around the world and is one of the leading causes of early death and disability in young children.
The disease causes progressive muscle weakness and paralysis and has four types, with type 1 being the most severe. Biogen has tested its drug on types 1-3, so the expansion of AveXis’ trials program should help it cover the same clinical ground as its rival as well as helping it catch up in Europe, where Spinraza got a green light last July.
AVXS‐101 is based on an adeno‐associated virus vector (AAV9) containing the SMN1 transgene that is designed to deliver a working copy of the gene to cells and cause long-term expression of SMN, a protein which is deficient in SMA. It works in a different way to Spinraza, which is an SMN2 splicing modifier, trying to increase the amount of functional SMN produced by the faulty gene.
“Our focus has always been to serve the SMA community, and our expanded clinical development program is designed to evaluate the impact of AVXS-101 in a broader set of SMA patients,” said Sukumar Nagendran, M.D., AveXis’ chief medical officer.
“We believe the year ahead has the potential to be one of significant clinical progress as we continue toward our ultimate goal of bringing AVXS-101 to the patients and families devastated by SMA.”
With no other approved therapies, Spinraza is gaining ground rapidly in the market and is already on course for blockbuster revenues with sales of $271 million in the third quarter of 2017. Analysts at Leerink have predicted it could bring in $2 billion by 2020, helped by a window of opportunity before other therapies become available.
Aside from AveXis, other companies are also trying to bring SMA drugs through clinical trials, including some Big Pharma heavyweights. Novartis has an SMN2 splicing modifier called branaplam in phase 1/2 testing for SMA type 1, while fellow Swiss group Roche has mid-stage studies ongoing for its neuroprotectant olexisome for types 2 and 3 SMA, as well as SMN2-targeted RG7916—partnered with PTC Therapeutics—in types 1-3.
Meanwhile, Cytokinetics is also active in this area with its fast skeletal muscle troponin activator (FSTA) CK-2127107, which works independently of SMN to boost muscle fiber responses and is in phase 2 testing for SMA types 2, 3 and 4.
Rett Syndrome and Genetic ALS with SOD1 Mutation Presentation
Executing on Our Strategy: Expanding Beyond SMA Rett syndrome (MECP2) and ALS (SOD1) are rare, life-threatening, neurological monogenic diseases that have significant unmet need and limited treatment options – none addressing the root cause
Licensed preclinical data from NCH generated by Chief Scientific Officer, Dr. Brian Kaspar, that demonstrate promising efficacy and safety
AveXis intends to submit IND applications for both indications in late 2018/early 2019
Licensed preclinical data from NCH generated by Chief Scientific Officer, Dr. Brian Kaspar, that demonstrate promising efficacy and safety
Obtained exclusive worldwide rights to AAV9 for Rett syndrome (MECP2) and a genetic form of amyotrophic lateral sclerosis caused by mutations in the superoxide dismutase 1 (SOD1) gene
AveXis intends to submit IND applications for both indications in late 2018/early 2019
AveXis will leverage its scalable manufacturing platform for these programs
Next Steps • AVXS-201 and AVXS-301 leverage AveXis’ scalable manufacturing platform by interchanging 1 plasmid ▪ Engineering runs at scale completed for AVXS-201 and AVXS-301 ▪ GMP campaign ongoing for AVXS-201 and scheduled for AVXS-301
• Complete remaining IND-enabling preclinical work
• KOL meetings for both AVXS-201 and AVXS-301 have occurred and clinical plans are forthcoming
• AveXis intends to submit IND applications for both indications in late 2018/early 2019
Under: Been on the sidelines for a bit holding (building) cash. Now that "BIGLEY" has rolled out the tax plan its time to jump in.
Dec 21, 2017 19:06:02 GMT -6
martyc: Looks like you are buying Msft again!
Dec 15, 2017 11:23:29 GMT -6
martyc: The news that Trump called Rupert to congratulate him sure seems to indicate that this is heading to approval
Dec 15, 2017 11:22:23 GMT -6
Under: DIS finally getting some traction.?
Dec 14, 2017 17:08:45 GMT -6
martyc: I took an entry level position in DIS. Will add eventually to overweight when it becomes clearer that the deal will go thru. Can't believe how well positioned they will be. 60% Hulu. 20% of content watched on NFLX they can pull. More in thread
Dec 14, 2017 11:05:16 GMT -6
Under: Great posts on $DIS
Dec 13, 2017 17:50:49 GMT -6
Under: $ROKU Citron on a war path.
Nov 28, 2017 15:11:20 GMT -6
Under: $HAS takeover bid for $MAT?
Nov 10, 2017 16:16:07 GMT -6
martyc: Not looking like the market will provide any discounted opp for SGMO. Call was just too professional and all signs indicate they are on a great path for commercialization. Happy with core but wish I had some trading shs
Nov 10, 2017 9:04:05 GMT -6
martyc: For anyone looking to find an entry point into SGMO, I'm almost hoping is sells off in next few days so I can add more. They are really clicking but the fact they haven't signed new deals might cause some to exit. Watching as I have room for trading shs
Nov 9, 2017 18:28:09 GMT -6
martyc: Been an interesting ride so far. I figured the Bears would be about this good but hoped the O wouldn't look so lame. Another building yr but still possible to get to 8-8 IMO
Nov 9, 2017 18:26:08 GMT -6
Under: whats up with your Bears this year Marty?
Nov 9, 2017 17:35:25 GMT -6
martyc: Hope you were long ROKU. I wanted to see Q first so missed out
Nov 9, 2017 7:08:53 GMT -6