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Post by jpg on Oct 14, 2015 22:04:52 GMT -5
I see the 'party logic' of using sildenifil by inhalation to be 'good to go' quickly if used for ED but certainly not for PH. There seems to be no obvious reason why sildenifil would need to be taken by inhalation or using technosphere for PH. I am rather certain that giving it by inhalation will be dangerous (and not just 'might be dangerous'). It would be like giving IV nitroglycerin or nitroprusside (don't do this at home kids...).
I haven't thought of this very much but a few musings about what to look for:
Using technosphere for PH would possibly be best suited to a molecule or peptide that can't be taken PO (because of digestive degradation or first pass metabolism), that has a relatively slow onset of effect (no inhalation peak effect) and relatively long half life (hours not minutes or seconds). The medication would also likely be generic but not used that much because of complexity (injections) or proprietary but injected (which would involve a partnership)?
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Post by lakers on Oct 15, 2015 4:01:24 GMT -5
I see the 'party logic' of using sildenifil by inhalation to be 'good to go' quickly if used for ED but certainly not for PH. There seems to be no obvious reason why sildenifil would need to be taken by inhalation or using technosphere for PH. I am rather certain that giving it by inhalation will be dangerous (and not just 'might be dangerous'). It would be like giving IV nitroglycerin or nitroprusside (don't do this at home kids...). I haven't thought of this very much but a few musings about what to look for: Using technosphere for PH would possibly be best suited to a molecule or peptide that can't be taken PO (because of digestive degradation or first pass metabolism), that has a relatively slow onset of effect (no inhalation peak effect) and relatively long half life (hours not minutes or seconds). The medication would also likely be generic but not used that much because of complexity (injections) or proprietary but injected (which would involve a partnership)? That's GSK Flolan 1. Blood vessel dilators (vasodilators). Vasodilators open narrowed blood vessels. One of the most commonly prescribed vasodilators for pulmonary hypertension is epoprostenol (GSK's Flolan). The drawback to epoprostenol is that its effects last only a few minutes. This drug is continuously injected through an intravenous (IV) catheter via a small pump that you wear in a pack on your belt or shoulder. This means that you'll learn to prepare your own medication mixture, operate the pump and care for the IV catheter. You'll need comprehensive follow-up care. Potential side effects of epoprostenol include jaw pain, nausea, diarrhea, leg cramps, as well as pain and infection at the IV site. Another form of the drug, iloprost (Ventavis), avoids many of these problems. Iloprost can be inhaled every three hours through a nebulizer, a machine that vaporizes your medication, making it far more convenient and less painful to use. And because it's inhaled, it goes directly to the lungs. Side effects associated with iloprost include chest pain — often accompanied by headache and nausea — and breathlessness. Read more: mnkd.proboards.com/thread/3694/flolan-migrained-imitrex-antiematic-zofran#ixzz3ocpxFKWG |
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Post by jpg on Oct 15, 2015 7:39:47 GMT -5
I see the 'party logic' of using sildenifil by inhalation to be 'good to go' quickly if used for ED but certainly not for PH. There seems to be no obvious reason why sildenifil would need to be taken by inhalation or using technosphere for PH. I am rather certain that giving it by inhalation will be dangerous (and not just 'might be dangerous'). It would be like giving IV nitroglycerin or nitroprusside (don't do this at home kids...). I haven't thought of this very much but a few musings about what to look for: Using technosphere for PH would possibly be best suited to a molecule or peptide that can't be taken PO (because of digestive degradation or first pass metabolism), that has a relatively slow onset of effect (no inhalation peak effect) and relatively long half life (hours not minutes or seconds). The medication would also likely be generic but not used that much because of complexity (injections) or proprietary but injected (which would involve a partnership)? That's GSK Flolan 1. Blood vessel dilators (vasodilators). Vasodilators open narrowed blood vessels. One of the most commonly prescribed vasodilators for pulmonary hypertension is epoprostenol (GSK's Flolan). The drawback to epoprostenol is that its effects last only a few minutes. This drug is continuously injected through an intravenous (IV) catheter via a small pump that you wear in a pack on your belt or shoulder. This means that you'll learn to prepare your own medication mixture, operate the pump and care for the IV catheter. You'll need comprehensive follow-up care. Potential side effects of epoprostenol include jaw pain, nausea, diarrhea, leg cramps, as well as pain and infection at the IV site. Another form of the drug, iloprost (Ventavis), avoids many of these problems. Iloprost can be inhaled every three hours through a nebulizer, a machine that vaporizes your medication, making it far more convenient and less painful to use. And because it's inhaled, it goes directly to the lungs. Side effects associated with iloprost include chest pain — often accompanied by headache and nausea — and breathlessness. Read more: mnkd.proboards.com/thread/3694/flolan-migrained-imitrex-antiematic-zofran#ixzz3ocpxFKWGMaybe but why use Technosphere for this? The half life is really short. What would be the upside over iloprost? There might be a detail about Iloprost that would be significantly improved by Technoshere? Simpler obviously as no need for the use of a nebulizer (which is a big advantage in itself) but theoretically the downside would be that you get more vascular uptake and quicker so might need to take it ore often than iloprost asit would be less pulmonary specific? Than again they might be able to modify the properties of the PK molecules to stay more in the lungs (more deposit and slower absorption)? |
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Post by me on Oct 15, 2015 10:09:49 GMT -5
Not my quote Lefty I said we were sleeping in separate bedrooms. For The Record. In case you wanted to quote me correctly I correctly quoted ricguy. The confusion was caused by the fact that if you delete language you are NOT responding to, there seems to be no way to delete the name of the author of that language. The confusion was that ricguy incorrectly quoted kball - ricguy put his "terd" comment within kball's comment, rather than below it. |
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Post by lakers on Oct 17, 2015 13:02:43 GMT -5
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Post by jpg on Oct 17, 2015 13:40:12 GMT -5
Pulmonary hypertension has been mentioned by management more then once. It does not appear on your list so I would speculate that this is because another entity is pushing for this? GSK and Flolan as you mentioned previously? Mannkind does not have the $ to move much (any) of this pipeline forward. To all of the above candidates are exciting (not so certain about Flolan if it is Flolan) but the Torrey Pines Pain Peptide and OXM would both be very long and expensive new molecular entities and need very deep pockets. GLP-1 has Sanofi with first rights so that is kind of tied up I would guess (and who knows if Sanofi wants to do this right now?). Without partners not much of this is going very far until we get traction with Afrezza. |
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Post by Deleted on Oct 17, 2015 14:16:02 GMT -5
Meaning no disrespect; but you sure don't sound like a Long to me at least. Aloha.
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Post by stevil on Oct 17, 2015 14:24:06 GMT -5
Meaning no disrespect; but you sure don't sound like a Long to me at least. Aloha. Lol |
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Post by lakers on Oct 17, 2015 15:00:53 GMT -5
Guiding Principle:
Looking at drugs which take advantage of TS features besides just eliminating the injection. Not practical to develop new chemical entities so working for next product to be a known drug. Occasionally look at NCE’s which are nice to look at but it would be a 10 year process.
10:00 Spent a lot of time and money on the consulting process to select 2 new applications / drug candidates. First indication would be pulmonary hypertension. This is a serious effort on the company’s behalf. The R&D activities are fully staffed and preclinical work has been/is being done. We can look forward to hearing more news about this soon but not at the moment. Licensing tech to other companies - have to be careful not create competitors to ourselves.
PAH being fast tracked ahead of Pain meaning that Mnkd may have had a silent partner w/ a known popular, commercial drug: Viagra, Cialis, Flolan. Torrey Pine has finished animal trial, waiting to start on human. But this is not a known drug. Imitrex Sumatriptan TS is more likely for migraine as it's popular. IMHO, PAH partner will be announced first. From Toledo, Colby deals, the upfront payment could be $200M plus 35% royalty when biotech is hot.
This is followed by Sumatriptan, rheumatoid arthritis (as announced w/ Tolero).
Humira (Adalimumab)
Humira is made by the pharmaceuticals giant AbbVie (NYSE:ABBV) and is approved for the treatment of, among other diseases, rheumatoid arthritis. The drug was made to inhibit production of TNF, or tumor necrosis factor, because TNF can cause severe inflammation and can impair the mobility of limbs and joints. Sales of Humira for full-year 2013 totaled a whopping $5.2 billion in the U.S. alone, a sales increase of nearly 18% year-over-year. The drug is taken by injection either by syringe or by injection pen usually weekly or biweekly in a new injection site every time.
Pfizer (NYSE:PFE) has developed an oral form of the drug called Xeljanz, but a combination of sluggish sales and rejection by European regulatory authorities who questioned the drugs benefit-risk profile have taken a lot of the air out of the potential for the drug. Xeljanz causes side effects that Humira does not cause, so even the fact that it's taken orally does not convince many to use it. The opportunity is still open for a non-injected therapy to come in and steal market share from Humira, which is expected to see peak annual sales of $11.2 billion in 2016. Additionally, the rheumatoid arthritis market is expected to grow to $18.2 billion in 2023.
Technosphere could be used to create an inhaled TNF inhibitor treatment that could compete with Humira for the sizable market that AbbVie's drug now dominates. The process would be simple: create a formulation with Technosphere particles and monoclonal antibodies that bind to and inhibit the TNF protein, and get FDA approval. Now I mean simple in theory, because actually making the formulation and getting passed regulatory hurdles is anything but simple. But the potential is there, and MNKD could benefit greatly from either creating this inhaled TNF inhibitor treatment itself or by licensing out Technosphere to another company that wants to try and develop the treatment.
#2 Neulasta (Pegfilgrastim)
Neulasta is a drug that patients take while undergoing chemotherapy, and the injection is taken once every chemotherapy cycle, which varies depending on the type of cancer and the patient. Specifically, Neulasta stimulates the bone marrow to produce more white blood cells to help fight off infection because chemotherapy leaves the immune system weak and vulnerable. The drug is produced by Amgen (NASDAQ:AMGN) and achieved sales of $3.5 billion for full-year 2013. Though sales growth has been slightly decreasing, Neulasta is the 9th best selling drug in the world.
There are currently no non-injectable alternatives to Neulasta, leaving the market wide open to an inhaled treatment to gain some market share. The same argument I made for Humira can be made here: there is a large market opportunity, a need for a non-injected treatment and a company with the technology to create an alternative treatment. This all translates into a great opportunity for a Technosphere drug.
#3 Copaxone (Glatiramer acetate)
Copaxone was developed by Teva Pharmaceutical (NYSE:TEVA) to treat multiple sclerosis (MS), an inflammatory disease that affects the nerve cells. The drug is thought to reduce the progression of the disease, which causes disability by affecting nerves in the spinal cord and elsewhere.
For full-year 2013, the drug generated sales of $4.3 billion, only a 1% increase year-over-year. Now, I don't know if you caught this, but sales of Copaxone are higher than #2 on this list, Neulasta. This is because Teva's best-selling drug is struggling with a lot of competition from both oral versions of the drug and generics, and Copaxone sales are expected to tumble 56% by 2016. However, the market opportunity for MS drugs is so large (the global MS market is projected to be $18.3 billion by 2018) that an inhaled MS treatment could carve out a good amount of market share.
#4 Rituxan (Rituximab)
Rituxan is a monoclonal antibody treatment that binds to the CD20 protein presented on B cells and kills the cells. The drug is used to treat diseases where B cells are either proliferating rapidly or becoming dysfunctional, such as lymphomas, leukemias and autoimmune diseases.
Rituxan is produced by Roche (OTCQX:RHHBY) and generated sales of $3.2 billion in the U.S. with a growth rate of 6% year-over-year. Rituxan is administered intravenously by a healthcare provider and dosage depends on the patient and the disease. Like most blockbuster drugs, many companies are out to create a generic copy of Rituxan, but so far none have been able to get past regulatory agencies.
An inhaled version of Rituxan could be a big hit, as the intravenous treatment now requires an appointment and a healthcare professional to administer the drug. A monoclonal antibody treatment or some other formulation taken through an inhaler to accomplish what Rituxan accomplishes could be a much more convenient alternative to what is now the only treatment on the market for this area.
Peppy said:
What interests me here is the use of technosphere and monoclonal antibodies.
monoclonal antibodies are being used to treat cancer.
. A deal structure that perhaps could best be described as “double-jointed,” in April new company Tolero Pharmaceuticals licensed exclusive worldwide rights to MannKind Corp.’s preclinical Bruton’s tyrosine kinase (BTK) inhibitor program, which Tolero believes could yield novel therapies for hematological cancers and inflammatory diseases. We think the deal could yield the companies this year's Roger in the alliance category.
MannKind, of course, is focused almost exclusively on its perennially troubled effort to develop a recombinant inhaled insulin product, Afrezza. The deal with Tolero puts development of the BTK compounds in the hands of the privately held, Utah-based biotech, but allows MannKind the ability to opt back in after Phase I if it likes what Tolero has uncovered. If MannKind opts back in to develop the compounds, the potential milestones and royalties would flow instead to Tolero.
“It’s a different model that we proposed and one that I think MannKind really liked,” Tolero Chairman and CEO Dallin Anderson told “The Pink Sheet” DAILY at the time. “It aligned incentives and made our negotiation progress very smooth. I think us proposing a structure that de-risked the opportunity for MannKind and gave them a chance to still be involved down the road helped us with not only terms but also to get to an agreement that makes sense for both parties.”
Tolero paid an undisclosed upfront amount with the potential for development, approval and commercialization milestones going to MannKind, along with tiered royalties on any product sales. The upfront and milestones could total $130 million, Anderson said. However, MannKind also retains the right to re-acquire the BTK assets at pre-specified terms up to 60 days after the conclusion of Tolero’s first Phase I study. If MannKind elects this option, it would assume all development and commercialization responsibilities and costs.
“BTK currently represents one of the most exciting therapeutic targets in oncology, and we feel that our collaborative approach to targeting BTK may uncover some novel utilities not yet fully realized,” Anderson said. He did not elaborate, however, on what those additional “utilities” might be.
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Post by jpg on Oct 17, 2015 16:47:26 GMT -5
Have we seen any news or money form Colby or Tolero?
I think we can safely discount these partnerships for the forceable future. Bringing them up does not inspire confidence as to the rest of the info you provide (the highly detailed 'conversation' you claim to have had with Roberta comes to mind...). I've called out a few people on this board as being 'overly pessimistic' but in your case I would go the other way and suggest you are being 'overly optimistic'.
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Post by lakers on Oct 17, 2015 17:26:25 GMT -5
Tolero was brought up to show a detail not well known to public, what is the precedence. Just gently ask Dey whether there will be a BoD meeting this Nov ... Many skeptics didn't do the heavy lifting but arm chair quarterbacking.
I was able to independently verify some information regarding Kevinmk's conversation w/ Matt, Dey before. Some were harsh on him w/o due diligence.
Some of his information was valuable to me. Some have condescending attitude towards Dye thinking what can a secretary tell you. She is actually quite nice, knowledgeable, professional as an IR rep. Depending on how you approach her, I glean some good information.
Hakan mentioned some companies signed NDA w/ Mnkd to deep dive on TS API. He has more information than he lets on. Hope he will reveal the silent partner for PAH.
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Post by lakers on Oct 21, 2015 23:38:34 GMT -5
TS PAH Competition IMPORTANT SAFETY INFORMATION FOR TYVASO Tyvaso is intended for oral inhalation only. Tyvaso is approved for use only with the Tyvaso Inhalation System The safety and efficacy of Tyvaso have not been established in patients with significant underlying lung disease (such as asthma or chronic obstructive pulmonary disease) and in patients under 18 years of age. Patients with acute pulmonary infections should be carefully monitored to detect any worsening of lung disease and loss of drug effect Tyvaso may increase the risk of bleeding, particularly in patients receiving anticoagulants In patients with low systemic arterial pressure, Tyvaso may cause symptomatic hypotension. The concomitant use of Tyvaso with diuretics, antihypertensives, or other vasodilators may increase the risk of symptomatic hypotension Hepatic or renal insufficiency may increase exposure to Tyvaso and decrease tolerability. Tyvaso dosage adjustments may be necessary if inhibitors of CYP2C8, such as gemfibrozil, or inducers of CYP2C8, such as rifampin, are added or withdrawn There are no adequate and well-controlled studies with Tyvaso in pregnant women. It is not known whether treprostinil is excreted in human milk The most common adverse events seen with Tyvaso in ≥4% of PAH patients and more than 3% greater than placebo in the placebo-controlled clinical study were cough (54% vs 29%), headache (41% vs 23%), throat irritation/ pharyngolaryngeal pain (25% vs 14%), nausea (19% vs 11%), flushing (15% vs <1%), and syncope (6% vs <1%) INDICATION Tyvaso is a prostacyclin vasodilator indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise ability. Studies establishing effectiveness included predominately patients with NYHA Functional Class III symptoms and etiologies of idiopathic or heritable PAH (56%) or PAH associated with connective tissue diseases (33%). The effects diminish over the minimum recommended dosing interval of 4 hours; treatment timing can be adjusted for planned activities. While there are long-term data on use of treprostinil by other routes of administration, nearly all controlled clinical experience with inhaled treprostinil has been on a background of bosentan (an endothelin receptor antagonist) or sildenafil (a phosphodiesterase type 5 inhibitor). The controlled clinical experience was limited to 12 weeks in duration. www.tyvaso.com/hcp/tyvaso-treprostinil/faq#isi-area |
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Post by jpg on Oct 22, 2015 1:10:09 GMT -5
I see what you are saying... Not a great amount of competition! Yes theoretically TS could certainly take all that market if it is as effective. Thanks for the info. |
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Post by lakers on Oct 22, 2015 2:22:27 GMT -5
Inhaled Treprostinil for the Treatment of Pulmonary Arterial Hypertension Five-year View The search for an effective oral prostanoid is ongoing. Initial encouraging results were seen for oral beraprost, with participants in the first placebo-controlled trial seeing improvements in 6MWD and dyspnea scores at 12 weeks. However, a subsequent trial, following subjects for 12 months, showed loss of efficacy in clinical end points after 6 months of therapy. Oral treprostinil has been the subject of three recent Phase III clinical trials – FREEDOM-M, FREEDOM-C and FREEDOM-C2 – as monotherapy and as an add-on to other drug classes. Preliminary analyses suggest benefits on exercise ability in the monotherapy group only. Although the eventual emergence of an oral prostanoid is anticipated, a continued role for inhaled prostanoids in PAH is still quite likely given their excellent tolerance and minimal overlapping side-effect profile. The potential for a more convenient inhaled delivery mechanism has been described. Acute administration of varying doses of treprostinil via a handheld metered-dose inhaler led to significant and sustained decreases in mPAP and PVR. A direct comparison of metered-dose inhaler and ultrasonic nebulizer-delivered treprostinil has not been performed in a single investigation, but studies utilizing similar protocols suggest similar effects. TRIUMPH I, the central study supporting inhaled treprostinil use, included a population of almost entirely functional class III patients. How the drug might fare in other populations, such as those with less severe disease, has not been established. Although minimally symptomatic PAH is rarely identified, the use of treprostinil (and other PAH therapies) for these individuals provides an interesting question. As more understanding about the pathogenesis of PAH is gained, treatment of those with early stages of disease or of those simply at risk for the disease, needs more attention. Treprostinil and other prostanoids can no longer be thought of as simple vasodilators and antiplatelet agents. Treprostinil's effects on smooth muscle proliferation and inflammation seem to be equally important, or potentially more important, in long-term outcomes. Demonstration of this type of benefit, however, requires longer, more expensive clinical work. If early action indeed proves fruitful in overturning the natural history of PAH, the inhaled prostanoids may have a niche as efficacious, well-tolerated therapies with few serious risks. Inhaled treprostinil's localized effects, theoretically maximal in regions of a well-ventilated lung, make it attractive as therapy for pulmonary hypertension related to underlying lung disease (WHO group 3). Case series involving other inhaled prostanoids have been promising. Eight patients with fibrosis and associated pulmonary hypertension demonstrated improvements in mPAP, PVR and cardiac output acutely with inhalation of epoprostenol. One patient in the series had presented with decompensated right-ventricular failure with functional class IV symptoms despite medical therapy. Intravenous epoprostenol improved mPAP, PVR, cardiac output and right ventricular ejection fraction, but significantly worsened gas exchange (PaO2 decrease from 72 to 62 mmHg, which was associated with a shunt increase from 5 to 23%). However, inhaled epoprostenol caused comparable improvements in the aforementioned hemodynamic parameters with additional improvement in oxygenation (PaO2 82 mmHg). Based on these findings, the patient was given long-term inhaled iloprost, with resulting improvements in hemodynamics, functional class and 6MWD at 1 year of therapy. Similar effects have been suggested in obstructive lung diseases. Dernaika et al. observed the effects on lung function, ventilatory parameters, gas exchange and exercise tolerance when inhaled iloprost was given to ten patients with chronic obstructive pulmonary disease and echocardiographic evidence of pulmonary hypertension. 6MWD improved in all patients (mean improvement of 50 m) while arterial oxygenation remained stable. Ventilatory equivalents for oxygen and carbon dioxide were significantly reduced, suggesting improvement in ventilation–perfusion matching. Success with longer-term use of inhaled iloprost has been described in case reports of patients with pulmonary hypertension secondary to chronic obstructive pulmonary disease and cystic fibrosis. www.medscape.com/viewarticle/768207_12REGULATORY AFFAIRS Inhaled treprostinil was approved by the FDA on 30 July 2009 for the treatment of WHO Group 1 PAH to improve walk distance in those with functional class III symptoms. In Europe, a marketing authorization application was submitted to the European Medicines Agency, but was subsequently withdrawn in February 2010. Inhaled Treprostinil for the Treatment of Pulmonary Arterial Hypertension Safety & Tolerability Common adverse effects following administration of inhaled treprostinil in the double-blind trial included cough (54%), headache (41%), nausea (19%), flushing (15%) and throat irritation (14%) or pain (11%). Over a 2-year treatment period in the TRIUMPH trial extension, adverse events resulting in drug discontinuation occurred in 19% of patients; these included worsening PAH, cough, headache, throat discomfort and pneumonia. No effect on pulmonary function studies or routine laboratory values has been seen. Given the antiplatelet effect, increased risk of bleeding, particularly in anticoagulated patients, is a potential concern. Hemoptysis, including a single fatal episode, was reported infrequently during the blinded and extension portions of TRIUMPH. It is unclear to what degree hemoptysis results from inhalation of treprostinil in particular, drug effect of treprostinil by any route, or underlying pulmonary hypertension unrelated to therapy. The systemic hemodynamic effects of inhaled treprostinil are minimal in the published literature. Unlike with intravenous and subcutaneous treatments, which can significantly affect systemic blood pressure, hypotension has not been routinely demonstrated with inhaled treprostinil. During one early study, administration of a single 120-µg dose (more than twice the currently approved dose) resulted in arterial desaturation; besides this, there have been no adverse effects on arterial oxygenation. Assessment of ventilation–perfusion matching in PAH patients following coadministration of sildenafil and inhaled treprostinil demonstrated no increase in shunt or areas of low ventilation/perfusion ratio. Expert Commentary While therapeutic possibilities for patients have greatly expanded over the last 10 years, PAH remains a diagnosis associated with high mortality, morbidity and functional impairment. Three major classes of medications have emerged, including the prostacyclin analogs. Administration of the prostanoids by intravenous and subcutaneous routes, while efficacious, carries risk. Inhaled treprostinil has demonstrated acute hemodynamic improvements with high selectivity of the pulmonary circulation. In addition to this local vasodilation, evidence supports an important disruption of the pathologic remodeling processes in PAH. Phase III work confirms inhaled treprostinil's efficacy in enhancing exercise ability and quality of life when initiated in patients already on monotherapy with oral bosentan or sildenafil. There have not been any controlled data published so far on the long-term use of inhaled treprostinil as monotherapy; although benefits may exist, routine application of this approach cannot yet be advocated. With strong academic rationale, combination therapy in PAH is an evolving area of research. Most, but not all, individual trials argue for an advantage of using two therapeutic classes. Consensus papers from both the USA and Europe now support consideration of combination therapy for those failing monotherapy. Thus, the use of combination therapy in PAH can only be expected to increase in the future. Inability to uptitrate oral or parenteral medications could be an important limitation on the efficacy of combination therapy in some patients. As agents predominantly promoting local effects, the inhaled prostanoids may hold a unique position as ideal add-on therapies with minimal additional systemic adverse effects. |
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Post by lakers on Oct 23, 2015 0:44:27 GMT -5
Lilly ER CC 10/22/15 In Bio-Medicines, we announced results from two Phase III rheumatoid arthritis studies evaluating baricitinib head to head against two of the most widely used RA treatments. In one study, baricitinib showed superior efficacy to methotrexate in treatment-na•ve patients. And in the second study it showed superior efficacy to adalimumab, the market-leading biologic in patients with inadequate response to conventional DMARDs. These are outstanding results. Our team is now squarely focused on global regulatory submissions. We'll present detailed data from these trials at the American College of Rheumatology meeting in San Francisco in November, and we will host an investor call on November 11 to review the results with you. David A. Ricks (Lilly Bio Medicines): Yeah, thanks for the question, Chris, on bari. We're very excited now that we have the full set of data in hand. Recall we have four separate Phase III programs, which really span the whole spectrum of rheumatoid arthritis, from refractory patients to biologics. Recall that was the first study we read out, and our study has, I think, a unique feature in it's a very real-world assessment. Many patients had failed on two or three or more biologics before entering that study, and still baricitinib showed very strong, robust efficacy. We then read out a study in conventional DMARD refractory patients. Again, baricitinib really helped patients who had been refractory to methotrexate and other conventional DMARDs. We then demonstrated superiority to really the established standard of care for disease modification, which is methotrexate, in the RA-BEGIN study, and most recently a superiority to adalimumab in DMARD-refractory patients, sort of this first-line biologic space. So I think we've gotten what we wanted when we started the program. And, to your question on safety, so far, through clinical trial observations, we're very reassured by the safety profile we see. So we're now onto submission. In terms of what to expect in the market, I think the RA market has some features where one would say this will not be sort of an overweight phenomena of share gain. You mentioned one, which is a natural caution on safety in any new drug where you're suppressing the immune system. We're very confident in the data we've produced on that dimension through our clinical trials, but understandably physicians like to see that play out over time, and I think that's been sort of the normal pattern in this market. As more reassuring safety data from a real-world setting is produced, doctors become more comfortable. It's also a very competitive space. We understand that, and we're prepared to compete in that. On the other hand, baricitinib I think offers a new choice, which is when I'm failing on inexpensive generic conventional DMARDs, rather than step two, a TNF, I have another alternative now, and that alternative appears to be superior to the standard of care in that setting. And there are a number of patients in that situation have not made that step two, anti-TNFs, for all kinds of reasons, and we'll be competing aggressively in that space. And so we like our hand. We obviously will have baricitinib for a while to come. We're stepping into a new market for Lilly; we want to do it right. And my view is I think we'll see good uptake. It won't be some overnight phenomena, but on the other hand, we do expect to make incremental gains as we enter the market. Humira (Adalimumab) Humira is made by the pharmaceuticals giant AbbVie (NYSE:ABBV) and is approved for the treatment of, among other diseases, rheumatoid arthritis. The drug was made to inhibit production of TNF, or tumor necrosis factor, because TNF can cause severe inflammation and can impair the mobility of limbs and joints. Sales of Humira for full-year 2013 totaled a whopping $5.2 billion in the U.S. alone, a sales increase of nearly 18% year-over-year. The drug is taken by injection either by syringe or by injection pen usually weekly or biweekly in a new injection site every time. Pfizer (NYSE:PFE) has developed an oral form of the drug called Xeljanz, but a combination of sluggish sales and rejection by European regulatory authorities who questioned the drugs benefit-risk profile have taken a lot of the air out of the potential for the drug. Xeljanz causes side effects that Humira does not cause, so even the fact that it's taken orally does not convince many to use it. The opportunity is still open for a non-injected therapy to come in and steal market share from Humira, which is expected to see peak annual sales of $11.2 billion in 2016. Additionally, the rheumatoid arthritis market is expected to grow to $18.2 billion in 2023. Technosphere could be used to create an inhaled TNF inhibitor treatment that could compete with Humira for the sizable market that AbbVie's drug now dominates. The process would be simple: create a formulation with Technosphere particles and monoclonal antibodies that bind to and inhibit the TNF protein, and get FDA approval. Now I mean simple in theory, because actually making the formulation and getting passed regulatory hurdles is anything but simple. But the potential is there, and MNKD could benefit greatly from either creating this inhaled TNF inhibitor treatment itself or by licensing out Technosphere to another company that wants to try and develop the treatment. AbbVie needs inhaled TS-based Humira to ward off Lilly for RA. Read more: mnkd.proboards.com/thread/3694/flolan-migrained-imitrex-antiematic-zofran?page=3#ixzz3pMnwBkSV |
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