|
Post by lakers on Jun 16, 2017 10:15:50 GMT -5
We need Tom Hanks gets on board as well. And Nick Jonas. It's just a matter of time.
|
|
|
Post by lakers on Jun 15, 2017 1:04:56 GMT -5
Afrezza Safety and Pharmacokinetics Study in Pediatric Patients clinicaltrials.gov/ct2/show/NCT02527265Pediatric PK Study is supposed to start 6/15/17. JDRF Round-Up with Aaron Kowalski Kowalski mentioned how much he likes using Afrezza, an inhaled insulin. “It’s almost a miracle drug for me.” But the company that created it, MannKind, “is having a hard time staying afloat. If MannKind fails, that’s a big deal for other companies spending money on better diabetes treatments.”) asweetlife.org/jdrf-round-up-with-aaron-kowalski/Next slide, the subsequent pediatric Phase 3 trial which we will file for pediatric indication, we will incorporate evidence not only from the PK study that we have conducted previously but as well as data from recent publications. These publications, as you can see on this slide, include dosing simulation work and the Afrezza with the artificial pancreas. The use of Afrezza with the artificial pancreas is impressive and promising and an area that we are actively investigating. When you take all of this data around the dosing and titration of Afrezza it helps to inform us as to the proposed pediatric protocol changes that we will need in the Phase 3 trial, which we believe will substantially improve study recruitment and retention and thereby expediting our filing dates. Read more: mnkd.proboards.com/thread/6959/afrezza-safety-pharmacokinetics-study-pediatric#ixzz4k383IUIqImproving Efficacy of Inhaled Technosphere Insulin (Afrezza) by Postmeal Dosing: In-silico Clinical Trial with the University of Virginia/Padova Type 1 Diabetes Simulator Roberto Visentin, PhD,1 Clemens Giegerich, MS,2 Robert Ja ̈ger, PhD,2 Raphael Dahmen, MD,2 Anders Boss, MD,3 Marshall Grant, PhD,4 Chiara Dalla Man, PhD,1 Claudio Cobelli, PhD,1 and Thomas Klabunde, PhD2 Abstract Background: TechnosphereÒ insulin (TI), an inhaled human insulin with a fast onset of action, provides a novel option for the control of prandial glucose. We used the University of Virginia (UVA)/Padova simulator to explore in-silico the potential benefit of different dosing regimens on postprandial glucose (PPG) control to support the design of further clinical trials. Tested dosing regimens included at-meal or postmeal dosing, or dosing before and after a meal (split dosing). Methods: Various dosing regimens of TI were compared among one another and to insulin lispro in 100 virtual type-1 patients. Individual doses were identified for each regimen following different titration rules. The resulting postprandial glucose profiles were analyzed to quantify efficacy and the risk for hypoglycemic events. Results: This approach allowed us to assess the benefit/risk for each TI dosing regimen and to compare results with simulations of insulin lispro. We identified a new titration rule for TI that could significantly improve the efficacy of treatment with TI. Conclusion: In-silico clinical trials comparing the treatment effect of different dosing regimens with TI and of insulin lispro suggest that postmeal dosing or split dosing of TI, in combination with an appropriate titration rule, can achieve a superior postprandial glucose control while providing a lower risk for hypoglycemic events than conventional treatment with subcutaneously administered rapid-acting insulin products. online.liebertpub.com/doi/pdfplus/10.1089/dia.2016.0128?download=true
|
|
|
Post by lakers on Jun 11, 2017 14:25:36 GMT -5
It's 2016 news, though. What's happened since? Do we know? Is Cipla's product dead in the water or are they just readying a new application for any day now? They explore other venues...
|
|
|
Post by lakers on Jun 11, 2017 14:11:28 GMT -5
the article was just too relevant not to in-line here lest it's deleted. BRIC expansion has started. A was trade marked in R. CIPLA’S INHALABLE INSULIN FAILS TO GET APPROVAL FOR TRIALS ON INDIAN PATIENTS Mon, 12/05/2016 - 16:27 EDT - The Economic Times RDF10 MUMBAI: Drug maker Cipla’s plan of developing a pump-delivered inhalable form of insulin has suffered a setback with an expert committee denying it permission to conduct trials on Indian patients. The panel has said the company’s preliminary data on safety and efficacy of the trial drug is insufficient. Cipla had based its application to the panel on the bioequivalence studies with Exubra, an inhalation drug and device combination that was being marked by Pfizer. Exubra was withdrawn from the market in 2007 due to slowdown in sales mainly because of issues revolving around product design. In November, the Subject Expert Committee — a group comprising experts in diverse fields of endocrinology and metabolism-—met and noted, "The firm (Cipla) has presented BA/BE (bioavailability/bioequivalence) study data and requested for phase IV study which is not acceptable and not scientifically justified with respect to inhaled insulin." Cipla declined to comment on the development. A year ago, Cipla’s application was examined by the same committee. It was directed to establish the safety, efficacy and dose finding study (phase I and II) before carrying out phase III study. That apart, Cipla was asked to provide safety and toxicological data from experimental/animal studies. "The firm should also carry out the coefficient of variation and stability of the device intended to be used for delivering of inhaled/powder insulin," the committee had then said in its report. A veteran in clinical research told ET the chances of Cipla getting a green signal appear slim given the issues related to studies to establish safety, efficacy and immunogenicity of the product in the new formulation. However, he said, carrying out large-scale studies and improving on the product design would enable Cipla to prove that it has bettered the safety and technology profile of the product. Although drug makers have explored technological disruptions to deliver insulin in forms other than needles and bring in convenience to the patients, those have met with little success. It was not just Pfizer’s Exubra that was junked. More recently, French drug maker Sanofi ended its deal with US-based Mannkind which had developed Afrezza. The product could not reach a scale due to lower-than-expected response from prescribers. Novo Nordisk, the biggest insulin maker in the world, recently dropped its project on oral insulin. Instead, it is focusing on a non-insulin drug that can be had as a tablet. Those failures, however, do not take away from Cipla’s capabilities in developing products using the inhalation technology. www.bullfax.com/?q=node-cipla’s-inhalable-insulin-fails-get-approval-trials-ind
|
|
|
Post by lakers on Jun 11, 2017 13:59:53 GMT -5
Cipla’s inhalable insulin fails to get approval for trials on Indian patients www.bullfax.com/?q=node-cipla’s-inhalable-insulin-fails-get-approval-trials-indRead more: mnkd.proboards.com/thread/8042/cipla-inhalable-insulin-approval-trials#ixzz4jimSKXhCMike gave a not-so-subtle hint, analogous to leaks by Comey:-). Cipla USA Inc., Inc., the US subsidiary of Cipla Limited, is the first Indian company to be approved by US FDA in 1985. Through a comprehensive partnership approach model, Cipla has been dedicated to providing access to medicines to US patients for over 30 years. The company has executed US partnerships and has commercialized products in the US. Cipla has supported the development of more than 170 ANDAs. Cipla has an active internal pipeline including several key respiratory products and other complex generics. Cipla launched its US label in January 2015. In September 2015, Cipla's UK arm, Cipla EU has entered into definitive agreements to acquire two US-based companies, InvaGen Pharmaceuticals Inc., and Exelan Pharmaceuticals Inc. Cipla Limited is an Indian multinational pharmaceutical and biotechnology company, headquartered in Mumbai, India.[3][4][5] Belgium, Surrey in the European Union, Miami, Florida, in the United States and Cape Town in South Africa; with manufacturing facilities in Goa (eleven), Bengaluru (one), Baddi (one), Indore (one), Kurkumbh (one), Patalganga (one), and Sikkim (one), along with field stations in Delhi, Pune, and Hyderabad[6] and Durban, South Africa. Cipla primarily develops medicines to treat cardiovascular disease, arthritis, diabetes, weight control and depression; other medical conditions. Cipla’s vision for the USA: US FDA approved drugs A global pharmaceutical company whose top priority is ensuring no patient shall be denied access to high quality & affordable medication and support. Cipla Limited is a global pharmaceutical company which uses technology and innovation to meet the everyday needs of all patients. For more than 70 years, Cipla has emerged as one of the most respected pharmaceutical names in India as well as across more than 150 countries. Our portfolio includes over 1500 products with 60 plus dosage forms across wide range of therapeutic categories. Cipla USA Inc., the US subsidiary of Cipla Limited, is based in Miami, FL. Our story in the US market started in 1984, when Cipla became the first Indian company to receive US FDA approval. Today in a tightly regulated environment, Cipla's 30 plus manufacturing facilities across India have been approved by major international regulatory agencies including US FDA, MHRA-UK, WHO, Department of Health-Canada, MCC – South Africa, ANVISA – Brazil, and PMDA – Japan. Cipla maintains world-class quality for its products and services across domestic and overseas markets, thereby ensuring that every patient has access to the best medicines in the world. cipla pharmaceutical companyThrough a comprehensive partnership model approach, Cipla has been dedicated to providing access to medicines at an affordable price for over 30 years in the US. The company has executed over 20 US partnerships and currently has commercialized products in the US. Cipla has supported the development of more than 170 ANDAs. Cipla USA brings a variety of technologies to the US markets in order to keep its ongoing commitment to provide access to high quality complex products at affordable prices. Cipla aims to continue to bring its wealth of pharmaceutical experience to develop innovative products and advanced drug delivery systems to offer meaningful healthcare solutions to patients in the US. www.ciplausa.com/about-us
|
|
|
Post by lakers on Jun 11, 2017 3:48:17 GMT -5
* Mannkind - pursuant to amendment, term of Amphastar agreement was extended from December 1, 2019 to December 31, 2023 * Mannkind - delivery schedule modified so that Amphastar will ship eur 2.7 million of insulin to co in q4 of 2017, eur 8.9 million in 2018, eur 11.6 million in 2019 * Mannkind - delivery schedule was modified to provide that amphastar will ship eur 15.5 million in 2020 and in 2021, and eur 19.4 million in 2022 and in 2023 * Mannkind corp - also granted Amphastar a right of first refusal to participate in development and commercialization of Afrezza in China Source text for Eikon: Further company coverage: (Reporting by Anil D'Silva) www.google.com/amp/mobile.reuters.com/article/amp/idUSFWN1DA16O
|
|
|
Post by lakers on Jun 11, 2017 3:15:49 GMT -5
|
|
|
Post by lakers on Jun 5, 2017 15:24:00 GMT -5
Other thing we're focused on is around the risk benefit or the safety profile of Afrezza. We are going to increase the awareness of lung function in cancer data or evidence that currently exists. There is a tremendous amount of missed information out there and these efforts will be directed to counteract that information.
Next let me talk a little bit about the long-term safety study. The protocol has been finalized and we're putting the operational components into place. As you may have been heard from me previously, we are aggressively managing the cost of this study while still driving to meet the FDA timelines. We are still on target to do so.
Dr Bode said "Most ENDOs won't prescribe because of the safety."
It's true from my meetings with PCPs and Endos. It's #1 impediment. When we can debunk that myth scientifically and officially, the floodgates will open wide.
|
|
|
Post by lakers on Jun 5, 2017 14:42:02 GMT -5
|
|
|
Post by lakers on Jun 2, 2017 21:21:15 GMT -5
Two more studies starting June 15, July/Aug 2017.
The dose optimization study is the Afrezza dynamic dosing study, which we're calling [AED-1] study. This protocol is very close to finalization and we're aiming for a July/August start with the possible Q4 completion, date available soon after.
We are putting together an Afrezza pediatric program that will include not only the regulatory required studies, but ancillary studies to address patient, provider and payer needs. We anticipate the first study in this program the PK-Start program I should say to start around June 15th. We are hoping to capitalize on the summer months to recruit these pediatric patients a little bit more quickly.
|
|
|
Post by lakers on Jun 2, 2017 20:54:39 GMT -5
Flash Glucose Monitoring: The Future Is Here online.liebertpub.com/doi/full/10.1089/dia.2017.0098www.clinicaltrials.gov/ct2/show/NCT03143816?term=Mannkind&rcv_s=05%2F01%2F2017&rank=1Satish K. Garg Halis Kaan Akturk © Satish K. Garg and Halis Kaan Akturk, 2017; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. Address correspondence to: Satish K. Garg, MD Barbara Davis Center for Diabetes - Adult Clinic 1775 Aurora Court, A140 Aurora, CO 80045 E-mail: satish.garg@ucdenver.edu Diabetes Technology & Therapeutics Vol. 19: Issue. S2: Pages. S-1-S-3 (Issue publication date: May 2017) doi.org/10.1089/dia.2017.0098New Rochelle, NY, May 30, 2017--Continuous Glucose Monitoring (CGM) sensors are now so accurate that two CGM devices, including the first approved "Flash Glucose Monitoring" system, have received regulatory approval for nonadjunctive use by individuals with type 1 diabetes to guide insulin dosing. The critical factors related to CGM accuracy, clinical implications of accurate CGM and flash glucose monitoring, and results of the most recent clinical trials assessing this technology are the focus of an article published as part of a special supplement on Flash Glucose Monitoring to Diabetes Technology & Therapeutics (DTT), a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. The supplement is available open access on the DTT website. In the article "Clinical Implications of Accuracy Measurements of Continuous Glucose Sensors," Timothy Bailey, MD, AMCR Institute, Escondido, CA, examines the different measures and approaches used to evaluate the accuracy of CGM devices. Dr. Bailey describes how in silico simulation studies are proving to be more useful for assessing the clinical effects of CGM accuracy than traditional clinical trials. He provides a valuable review and comparison of recent clinical studies that have compared various strategies for using different types of CGM devices, including a flash glucose monitoring device that is approved for use in Europe (with a professional version only approved in the U.S.). In the Editorial "Flash Glucose Monitoring: The Future Is Here," DTT Editor-in-Chief Satish Garg, MD, Professor of Medicine and Pediatrics at the University of Colorado Denver (Aurora) presents several reasons for the early success and rapid uptake of flash glucose monitoring: low cost; no calibration needed (factory calibrated for 14 days of continuous use); accurate data available on demand; similar/lower mean absolute relative difference (MARD) throughout 14 days of use. Dr. Garg states, "We hope that flash glucose monitoring (FreeStyle Libre personal) will be made available soon in the United States after approval by the FDA. We also hope that it is approved as 'nonadjunctive.'" ### This supplement was supported by an educational grant from Abbott Diabetes Care Inc. About the Journal Diabetes Technology & Therapeutics (DTT) is a monthly peer-reviewed journal that covers new technology and new products for the treatment, monitoring, diagnosis, and prevention of diabetes and its complications. Led by Editor-in-Chief Satish Garg, MD, the Journal covers topics that include noninvasive glucose monitoring, implantable continuous glucose sensors, novel routes of insulin administration, genetic engineering, the artificial pancreas, measures of long-term control, computer applications for case management, telemedicine, the Internet, and new medications. Tables of contents and a free sample issue may be viewed on the Diabetes Technology & Therapeutics (DTT) website. DTT is the official journal of the International Conference on Advanced Technologies & Treatments for Diabetes.
|
|
|
Post by lakers on Jun 1, 2017 1:02:36 GMT -5
Another hint is perusing the next 2 countries Pfizer shipped Exubera or got approval for after the U.S. Just check the date. They are public info. From a 2006 PR: Exubera is the first insulin, and first ever biotechnology-based medicine to treat a systemic disorder, that can be administered without an injection. It is the only inhaled insulin to be approved for use in clinical practice in the European Union, U.S. , Brazil and Mexico, and it is pending approval in several other countries...Exubera is currently available in the U.S., United Kingdom, Ireland and Germany.ir.nektar.com/releasedetail.cfm?releaseid=210848Mnkd follows the same playbook as Pfizer in ex-US expansion, the South America Brazil.
|
|
|
Post by lakers on May 29, 2017 20:55:54 GMT -5
The company that manufacturers the Afrezza filling and assembly lines - Harro Hofliger - is located in Germany. I recall Matt stating a few years ago that it takes approximately 6-9 months to build and install, followed by testing and certifying the equipment. It would make more sense to order new equipment and ship it to a facility in China than for MannKind/Amphastar to disasemble, ship and re-assemble an existing fill line. Matt also stated the newer models are much faster than the originals, which is another reason to order new equipment and because of the potential sales volume potential for Afrezza in China, I doubt that one fill line would be able to keep up with demand anyway. Resource: www.hoefliger.com/en/applications/inhaling-insulin-instead-of-injecting/I agree with your assessment. Besides, Danbury needs to provide for ME, new North/South America countries.
|
|
|
Post by lakers on May 29, 2017 18:53:40 GMT -5
Insulin Min purchase part of CTO with AMPH revealed in AMPH's filing which corroborated significant international expansion. Expanding on this with a look at Amphastar SEC filings: In November 2016, the Company amended the Supply Agreement with MannKind, whereby MannKind's aggregate total commitment of RHI API under the Supply Agreement has not been reduced; however, the annual minimum purchase commitments of RHI API under the Supply Agreement have been modified and extended through 2023, which timeframe had previously lapsed after calendar year 2019. Specifically, the minimum annual purchase commitment in calendar year 2016 has been cancelled, and the minimum annual purchase commitments in calendar years 2017 through 2023 have been modified to be €2.7 million ($3,019,100) of insulin in the fourth quarter of 2017, €8.9 million ($9,951,847) in 2018, €11.6 million ($12,970,946) in 2019, €15.5 million ($17,331,868) in 2020 and in 2021, and €19.4 ($21,692,789) million in 2022 and in 2023. MannKind may request to purchase additional quantities of RHI API in excess of its annual minimum purchase commitments. The Supply Agreement Amendment also shortened the required expiry dates for RHI API delivered to MannKind pursuant to the Supply Agreement, (ii) modified the timing of MannKind's payment for the minimum annual purchase commitment in calendar year 2017, and (NASDAQ:III) added a pre-payment requirement for purchases of RHI API by MannKind in calendar years 2017 and 2018. The amendment can be renewed for additional, successive two-year terms upon 12 months' written notice, given prior to the end of the initial term or any additional two-year term. Concurrently with the amendment of the Supply Agreement, the Company amended the Option Agreement with MannKind, whereby the amendment to the Option Agreement extends the timing for payment of the capacity cancellation fee for 2017 and decreases the amounts payable as capacity cancellation fees for 2018 and 2019 in the event MannKind fails to exercise its minimum annual purchase option for any given year. The Company recognized the cancellation fee for 2017 of $1.5 million in net revenues in its consolidated statement of operations for the year ended December 31, 2016, and subsequently collected on this receivable. In addition to, and in consideration of the amended timeframe and other amendments contained in the amendment to the Supply Agreement in the amendment to the Option Agreement, the Supply Agreement Amendment provided the Company right of first refusal to participate in the development and commercialization of Afrezza ® in China through a collaborative arrangement. seekingalpha.com/instablog/175233-spencer-osborne/4992182-mannkind-contract-amphastar6.5 Right of First Refusal in China. In consideration of the amendments contained in this Second Amendment and in the Option Amendment, MannKind hereby grants Amphastar the right of first refusal to participate in the development and commercialization of Afrezza in China through a collaborative arrangement. Specifically, Amphastar and MannKind agree that MannKind will not commence the process of obtaining approval of Afrezza in China without first providing Amphastar with (NYSE:I) at least ninety (90) days prior written notice of MannKind's intention to commence the process of obtaining approval of Afrezza in China, and (ii) if Amphastar confirms its interest in collaborating in the development or commercialization of Afrezza in China in writing within thirty (30) days of receipt of MannKind's notice, then the Parties shall reserve sixty (60) days to negotiate in good faith the terms of such a collaborative arrangement for Afrezza in China. In the event that the Parties are unable to agree on commercial terms for a collaborative agreement after the sixty (60) day negotiation period, then MannKind shall have the right to negotiate a collaborative agreement with another party ("Competing Terms"). MannKind shall present the Competing Terms to Amphastar in writing, and within sixty (60) days of receipt of the Competing Terms, Amphastar shall have the option to either decline to match the Competing Terms, or (ii) agree to match the same Competing Terms and enter into a collaborative agreement with MannKind in China. The existence of this protects both sides. It gives Amphastar the ability to be the partner in China. It helps MannKind ensure a stronger deal from a potential suitor. Cost of Goods Sold would be lower in Q1, Q2, and Q3 of this year because there is no insulin buy.
|
|
|
Post by lakers on May 29, 2017 15:15:21 GMT -5
|
|