Search This Blog

Monday, September 3, 2018

Portola Submits Med Manufacturing Prior Approval Supplement to FDA


Portola Pharmaceuticals, Inc. (Nasdaq:PTLA) today announced the submission of a prior approval supplement (PAS) to the U.S. Food and Drug Administration(FDA) for the large-scale Generation 2 manufacturing process for Andexxa [coagulation factor Xa (recombinant), inactivated-zhzo].
If approved, the PAS will allow for broad commercial launch of Andexxa in the United States.
Andexxa received both U.S. Orphan Drug and FDA Breakthrough Therapy designations, and was approved on May 3, 2018 under the FDA’s Accelerated Approval pathway. It is the first and only antidote indicated for patients treated with rivaroxaban and apixaban, when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding.
‘We are pleased that patients are already benefitting from access to our limited supply Generation 1 product via an Early Supply Program,’ said John Curnutte, M.D., Ph.D., interim co-president of Portola and head of research and development. ‘With the recent completion of three successful Generation 2 manufacturing campaigns, we have enough supply to stock more than 1,000 hospitals, and we look forward to working with regulatory authorities to achieve our goal of expanding patient access to this potentially life-saving medicine.’
Based on FDA timelines, the Company expects a final decision on the PAS in Q1 2019. In Europe, andexanet alfa received a positive trend vote from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency in February 2018. Pending the submission of additional data requested by the CHMP, a final CHMP opinion is expected in Q4 2018 with the potential for approval in Q1 2019.

MicroPort Stent Trial Data to Be Published in The Lancet


MicroPort Scientific Corporation (“MicroPort®”, HK:0853) announced today that the clinical trial results for its Firehawk® Rapamycin Target Eluting Coronary Stent System (“Firehawk®”) which conducted a multi-center, randomized controlled trial called TARGET AC has been published online in The Lancet, a world leading medical journal currently ranked second out of 154 journals in the Medicine, General & Internal subject category. The title of The Lancet publication regarding Firehawk® is Targeted therapy with a localised abluminal groove, low-dose sirolimus-eluting, biodegradable polymer coronary stent (TARGET All Comers): a multicentre, open-label, randomised non-inferiority trial.
The TARGET AC trial was a prospective, multi-center, randomized controlled clinical trial consisting of entirely European based patients. This clinical study enrolled its first patient in December 2015 and completed enrollment of its last patient in October 2016. In total, there were 1,653 patients enrolled from 21 clinical study sites throughout Europe including countries such as the United Kingdom, France, Spain, Italy, Belgium, the Netherlands, Poland, Germany, Austria and Denmark.
Firehawk® met the trial’s non-inferiority primary endpoint which was the TLF (Target Lesion Failure) rate at 12 months as compared to the control arm represented by the Xience stent family, 6.1 percent versus 5.9 percent (pnon-inferior=0.004), respectively. No statistically significant differences in TLF components were observed between the two stents. The following data were also observed at 12 months post implantation for the Firehawk® stent and Xience family stents, respectively: cardiac death (1.2 percent vs. 0.9 percent, p=0.60), myocardial infarction (MI) related to the target vessel (4.5 percent vs. 3.9 percent, p=0.59), ischemia-driven target lesion revascularization (TLR, 1.2 percent vs. 2.4 percent, p=0.08), stent thrombosis rate (ARC definite, 1.2 percent vs. 1.2 percent, p=0.99). Of note, the TLR rate was lower in the Firehawk® stent group and the stent thrombosis rate was the same for both Firehawk® and Xience family stents.
“TARGET AC confirms that the Firehawk®, a low dose sirolimus eluting biodegradable polymer DES, is safe and effective across a broad spectrum of patient and lesion complexity,” said lead author Professor Alexandra Lansky, Yale University School of Medicine.
“This is a landmark achievement by MicroPort® given that this is the first time that clinical data from a China manufactured drug eluting stent has been published in such a prestigious medical journal such as The Lancet,” said Dr. Zhaohua Chang, Founder Chairman and CEO of MicroPort®. “With the Firehawk® clinical results having been validated in such a rigorous peer-reviewed publication, clinicians and patients should have every confidence in the safety and efficacy of Firehawk® to treat patients with coronary artery disease. We strongly believe and expect that the Firehawk® stent will be used to save millions of patients globally in the years to come. As a company, MicroPort® will continue to be at the forefront of developing and providing revolutionary medical technology solutions to meet the unending demand for health and longevity in extending patient lives.”
Firehawk® is MicroPort®’s third generation drug eluting stent developed to treat patients with coronary artery disease. The unique innovation of Firehawk® is the design where the drug and biodegradeable polymer are eluted from micro grooves laser-cut on the abluminal side of the stent struts. The total surface area of all the grooves is less than 5% of the total surface area of the stent struts while 95% of the stent surface area remains bare metal. This target eluting design allows Firehawk® to achieve the same level of clinical efficacy as the “best-in-class” drug-eluting stents, but with the lowest drug dosage. Furthermore, Firehawk® overcomes the late thrombosis event weakness inherent in drug eluting stents while maintaining a long-term safety profile commensurate of bare metal stents.

Bionomics to Host Call on Lead Med, Treatment of Agitation in Elderly Patients


Bionomics Limited (ASX:BNO, OTCQX:BNOEF), a global, clinical stage biopharmaceutical company, today announced that it will host a virtual Key Opinion Leader (KOL) event focused on BNC210 and the treatment of agitation in elderly patients, on Monday, September 10, 2018 at 8:30 a.m. ET.
The event will feature a keynote presentation from:
  • • Paul B. Rosenberg, M.D., Professor of Psychiatry and Behavioral Sciences; Johns Hopkins University School of Medicine; Associate Director, Memory and Alzheimer’s Treatment Center Division of Geriatric Psychiatry and Neuropsychiatry; Johns Hopkins University School of Medicine
Bionomics’ management will also provide an overview of the Company’s recent pipeline progress, including its ongoing Phase 2 study of BNC210 in PTSD. In addition, the conference call will feature a fireside chat discussion chaired by H.C. Wainwright Managing Director Joe Pantginis, Ph.D.
In order to participate in the conference call, please dial 866-866-1333 if calling within the US and +1-866-866-1333 if calling outside the US and refer to confirmation number 47442178. A live audio webcast can be accessed on the Bionomics website,www.bionomics.com.au.An archived replay will be available for 30 days after the live event concludes.

Addex Preclinical Med Data Shows Promise in Severe Panic Disorders, PTSD


Preclinical and Adhoc Clinical Data Published in Molecular Psychiatry
Addex Therapeutics (SIX: ADXN), a leading company pioneering allosteric modulation-based drug discovery and development, announced today publication of a study demonstrating the potential therapeutic effect of ADX71149 (JNJ-40411813), a selective metabotropic glutamate type 2 (mGlu2) receptor positive allosteric modulator (PAM), in severe panic disorders and post-traumatic stress disorder (PTSD). Data published in the leading peer-reviewed journal, Molecular Psychiatry, shows that a panic-prone state leads to specific reduction in mGluR2 function within the amygdala network in the brain and facilitates the fear response, suggesting treatment with an mGluR2 PAM, such as ADX71149, could provide an effective alternative in these difficult to treat disorders. ADX71149 is licensed to Janseen Pharmaceuticals Inc., and is currently being prepared for a Phase 2 study in patients with epilepsy.
“This excellent research by Dr Shekhar and his co-authors at Indiana University School of Medicine supports the potential of ADX71149 in additional, difficult to treat psychiatric disorders. We have hypothesized for some time on the multifaceted effects that the fear response has on certain areas of the brain but are now able to pinpoint specific molecular changes in the amygdala network, an area of the brain integrally involved in fear and generating a panic response,” commented Robert Lütjens, co-head of discovery at Addex. “We continue to study the role our allosteric modulators play in all types of neurological disorders and believe our approach could lead to safer and potentially more effective treatments.”
In the publication, the researchers show that optogenetic stimulation of the amygdala region enhances acquisition, delays the extinction of conditioned fear, and strengthens long-term fear memories. Using electrophysiological approaches on amygdala slices taken from panic-prone rats, an increase in the excitability of principal neurons in the amygdala was observed. Pretreatment with the selective mGluR2 PAM, JNJ-42153605, reduced the frequency of spontaneous excitatory postsynaptic potentials and significantly reduced glutamate release within the amygdala region.Treating panic-prone rats with the ADX71149 resulted in prevention of sodium lactate-induced panic responses and normalized conditioned fear extinction deficits. These findings led the researchers to re-analyze the results from a Phase 2 clinical study that evaluated ADX71149 as an adjunctive treatment for major depressive disorder (MDD) with significant anxiety symptoms. The post-hoc analysis shows that a subset of patients with panic disorder symptoms and treated with ADX71149 demonstrated remission of their panic symptom scores.

Inovio, Korean Partner Dose 1st Subject In Trial for World’s 1st Hep C Vaccine


Inovio Pharmaceuticals, Inc. (NASDAQ:INO) and GeneOne Life Science (KSE: 011000) today announced they have dosed the first patient in a Phase 1 study designed to evaluate a preventive vaccine against hepatitis C infection. Recruitment has already begun in South Korea, where GeneOne is responsible for conducting and funding this Phase 1 trial to assess the ability of Inovio’s hepatitis C vaccine (GLS-6150) to boost immunity in people who have been treated and cleared of the virus. Pending study results, Inovio’s vaccine could be employed to prevent infection and re-infection.
This jointly developed, open-label, Phase 1 study of GLS-6150 will evaluate a total of 24 persons who have a sustained virologic response (SVR) following treatment for Hepatitis C (n=8 per group) and an additional 8 healthy controls to compare immune responses. Subjects will receive one of two doses of vaccine, 1 or 2 mg, administered intra-dermally and followed by electroporation with Cellectra-3P device. Vaccinations will occur as a 3 dose priming series (0, 4, 12 weeks) or as a 2 dose priming series (0, 8 weeks) and followed by a booster dose at 6 months. Final study visit is 4 weeks following the 6 month booster vaccination.
Dr. J. Joseph Kim, Inovio’s President & CEO, said, “Developing the first successful vaccine against hepatitis C virus is a highly ambitious endeavor but a truly impactful effort for global health as well as being transformative for us commercially. The key to a successful hepatitis C vaccine will be its ability to activate the body’s immune system to prevent or treat infection by a virus with multiple or ever-changing strains. Inovio’s innovative DNA-based technology platform is uniquely positioned to address this challenge and it has been optimizing over the last several years in demonstrating strong in vivo immune responses against very tough-to-treat viruses like HIV, Zika and flu. We are very excited to launch this study with GeneOne’s funding and execution in Korea and we look forward to the data in 2019.”
Many insurers and governments, including the U.S., are seeking ways to control the high medical costs of treating hepatitis C infection and frequent re-infections especially in at-risk patient populations.  Efforts to develop a hepatitis C vaccine started more than 25 years ago when the hepatitis C virus was first identified. Progress has been slow because the hepatitis C virus is more variable than are the viruses that cause hepatitis A and B. The hepatitis C virus occurs in at least six genetically distinct forms (genotypes) with multiple strains. About 50 subtypes have been identified to date. Inovio’s synthetic DNA vaccines have an advantage over inactivated or attenuated virus products since they are not limited to one specific strain of virus. As such, they are well matched against viruses with multiple strains and have demonstrated in clinical trials the ability to produce broad-spectrum immune responses against numerous strains of targeted pathogens.

Smiths rebuffs ICU’s latest offer for medical division


ICU Medical Inc’s new offer to buy British engineering firm Smiths Group Plc medical division for 2.8 billion pounds ($3.60 billion) was rejected by Smiths’ board, Sky News reported on Monday.

The deal would have consisted largely of cash and partly of ICU Medical stock, Sky News said. http://bit.ly/2NiaAmU
The U.S.-based healthcare group tabled a written offer last month for Smiths Medical that would have also given Smiths a stake in the combined business, Sky News added.
ICU Medical has been flexible about the amount of stock that would be part of the transaction, which would have valued Smiths Medical at between 2.5 billion pounds to 2.8 billion pounds, Sky News said.
It is unclear where the rejection of ICU’s most recent offer leaves the two sides, according to the report.
Sky News said a source close to Smiths pointed out that talks must be ongoing ‎given the absence of a stock exchange announcement to the contrary.
The new proposal was made by ICU Medical soon after the two companies were close to abandoning their discussions about merging their healthcare divisions, according to the report.
Smiths Group and ICU Medical did not immediately respond to requests for comment outside regular business hours.

Celgene Shares Ready for a Recovery?


It hasn’t been a particularly good year for Celgene. In late 2017, the company abandoned a late-stage Crohn’s disease drug, GED-0301, and two clinical trials associated with it. This resulted in a drop in company share prices. The company then slashed its 2020 guidance, citing “certain market dynamics and recent pipeline events.” Then, completely unexpected for a company of Celgene’s size and stature, the U.S. Food and Drug Administration (FDA) issued a Refusal to File letter regarding its New Drug Application (NDA) for its multiple sclerosis drug ozanimod. Since October 2017, shares have dropped 37 percent.
Are company shares about to bounce back? Some analysts think so.
Keith Speights, writing for The Motley Fool, notes that Celgene’s pipeline, although promising, carries a great deal of risk. “Market research firm EvaluatePharma estimated cumulative sales for pipeline candidates between 2018 and 2024 as a percentage of total revenue for all major drugmakers,” he writes. “Celgene ranked at the top of the list, indicating the highest pipeline risk.”
And as the Refusal to File letter suggests, some of the company’s issues may be management-related. In addition, some of the company’s patents are tangled up in lawsuits, and if the company should lose, significant revenue could be in jeopardy.
None of this sounds like good news for Celgene investors. But Speights writes, “The flip side to Celgene’s pipeline risk is that there are many very promising treatments under development. Celgene expects to launch 10 blockbuster drugs over the next few years. Half of those could generate peak annual sales of $2 billion or more. In total, Celgene could add another $16 billion or more in peak revenue through 2030 just with these 10 pipeline candidates.”
Some of those pipeline compounds look very solid. And the company has made changes to its executive team, with Mark Alles, the company’s chief executive officer, stating there is “a more accountable structure” in place.
In terms of the lawsuits around the company’s Revlimid, Speights writes, “It’s important to know that this isn’t the first time Celgene has fought off a potential generic rival.”
Serge Berger, writing for Yahoo! Finance, takes a more technical approach, but comes to similar, though perhaps not quite as optimistic, conclusions. He writes, “On the multiyear weekly chart we see that Celgene stock has been in a sea of hurt over the past twelve months or so. After topping out at a fresh all-time high in September 2017, the stock fell off a cliff and ultimately in the spring of 2018 broke before its multiyear horizontal support line in the low to mid $90s.”
He goes on to say, “Over the past couple of months the stock has managed to claw back higher, but so far it is only getting back near this previous area of horizontal support … which now may or may not become technical resistance.”
A daily chart analysis notes a recent rally, which has brought the company back through intermediate-term moving averages and appears to be working its way over the 200-day moving average. Berger writes, “One could simply buy the stock here in the low $90s for a next upside target close to $97 and using any meaningful one-day bearish reversal as a stop loss signal. Alternatively and a trade with much higher probability of steady success, one could look to sell out of the money put option spreads on Celgene stock, simply making the bet that the stock won’t fall much from here.”
Celgene has projected its revenue will grow at a compound annual growth rate (CAGR) of 14.5 percent through 2020 and predicted earnings-per-share (EPS) of about 19 percent annually. Those are consistent with Wall Street expectations, numbers that should make most investors optimistic.
Speights notes, “As a result of the big sell-off over the past year, Celgene stock now trades at less than 8.7 times expected earnings. Its price-to-earnings-to-growth ratio is a super-low 0.53. You won’t find other biotechs with the revenue and earnings that Celgene generates with stocks so attractively valued.”