NACF annual conference in Tucson Oct 8-10. Program Agenda includes lots of presentations relevant to new Ivacaftor, Orkambi clinical trial results on long term benefits in rollover trials, as well as reports on progress with Pharion drug licensed to Vertex and in clinical trials as monotherapy for all CF patient mutations, prior to combination treatment with Orkambi and 661/770 to be started next year.
3rd qtr earnings and conf call week of Oct 26, Will give indication of rapidity of uptake of Lumacaftor by the 508dd population and an estimate of revenue growth for coming quarters. (Judging
EU approval of Orkambi in 4th quarter and addition of EU sales of Orkambi throughout 2016 as each EU country works out pricing as they did with Ivacaftor.
From VRTX most recent 10Q filing:
We submitted a Marketing Authorization Application, or MAA, for ORKAMBI for the treatment of patients with CF twelve years of age and older who are homozygous for the F508del mutation in their CFTR gene to the European Medicines Agency, or EMA, in November 2014. We do not expect significant net product revenues from ORKAMBI from ex-U.S. markets in 2015 due to the reimbursement discussions that will be required in these markets following its potential approval by the European Commission in the fourth quarter of 2015. We believe that there are approximately 12,000 patients with CF twelve years of age and older who are homozygous for the F508del mutation in Europe.
Thank all of you for sharing your experience. Nick Jonas promotion will certainly heighten awareness of using CGM among the young Type 1 Diabetics and the ease of use, accuracy, connectivity and comfort of the G5 DXCM sensor will drive sales for the next several quarters. The DXCM partnership with Tandem and JNJ'/Animus insulin pumps will further boost sales. The FDA only requires twice a day finger stick validation of the DXCM G4 sensor with Tandem's insulin pump. It's only a matter of time before fingersticks have been eliminated by CGM. The only question in my mind is whether a bigger player in the glucose testing market e.g. JNJ will make a takeover bid for Dexcom?
Way overblown reaction by the market to factors already well known or without obvious merit. Ironic that comments by the Piper analyst, who just 2 days earlier reiterated his BUY rating on VRTX, (something not mentioned in any of the news flow by financial press) is being used as the excuse for yesterday's drop because the analyst thought that GILD would not likely pursue a takeover of VRTX because it is not a 'good fit' for a merger. Some reports claimed a 20% premium for such a potential takeover was baked into the share price of VRTX. Who but shorts or options players betting on a drop in VRTX share price would want to push such comments in the financial press on a triple witch options expiration day, coincident with a big drop in the market averages following the fed's decision to delay raising interest rates due to concerns of the slowing world economy not evident in the U.S.?
Lastly the announcement of an investigation by a law firm specializing in shareholder class action lawsuits against public corporations for an unspecified allegation of breach of fiduciary duty by VRTX BOD in the middle of yesterday's overall bad market day, seemed also timed for maximum negative effect on VRTX share price during a general market sell-off. Hard to prove market manipulation but one has to wonder about the timing of these 'reports' and motivation of the people releasing them on this particular day. Lastly, the comments about potential competitors like Pro QR Therapeutics and GLPG never mention the facts that VRTX is actively pursuing improvements in it's CF treatments, is years ahead in it's program compared to these unproven competitors and ignore the points made by Michael Yee from RBC capital in yesterday's Barron's article about the pipeline from VRTX likely to make the barriers to competitors extremely high. Lastly the Pharion drug which can be used in the entire CF population without respect to mutation type will augment of the benefit of the VRTX CF drugs.
Third, thanks again for a beautiful explanation of the physiology and the mechanism of the synergy to be expected in pairing VX 371 with Orkambi. VX 371 Should improve the beneficial effect in all VRTX clinical trials combining correctors with a potentiator of CFTR in all CF mutations. And in the next few weeks at the NACF meeting in Tucson, we will be hearing about the benefits and safety using VX 371 as monotherapy in all CF mutations, and can then learn about the timeline of initial clinical trials studies combing Orkambi with VX 371 in the 508 homozygous CF population..
Each province in Canada negotiates it's own purchase price for meds. They are not purchased beyond what is used in each province on it's citizens based on a strict budget. They usually get a substantial discount compared to list price, but then so does Medicaid subsidized patients in the US, as do patients treated in Europe and Australia. Negotiated discounts for 'bulk purchasing' has been in play for years for large insurers (commercial and government run healthcare systems)..... none of this is new.
The initial days on CFTR correctors/potentiators involve hydrating and loosening of dried out chronically infected mucus secretions in the lungs of CF patients. The sicker the patient was at baseline (ie FEV-1 less than 40% of predicted) before starting Orkambi, the more symptomatic they are likely to be initially as they start to cough up all that dried out phlegm stuck in their bronchial tubes. Once that #$%$ is finally coughed up, sometimes requiring antibiotics and even occasional in-hospital treatment, the patients tend to stabilize and improve significantly with decreased number of infections, better exercise tolerance, weight gain, and somewhat improved FEV1 leading to decreased subsequent hospitalization and slowing the progression of loss of pulmonary function that naturally occurs without Orkambi. That's why the rollover study at the completion of the Phase 3 Orkambi clinical trials had well over 90% voluntary enrollment (over 1000 patients) whose sustained benefit from treatment has already been reported and will be again published after 2 years on treatment next month and the NACF national meeting. The anecdotal blogs of CF patients first starting Orkambi reflect the same experience as in the clinical trials, with patients with more severe disease having an initial harder time coughing up the old mucous do to their advanced lung disease, but those with higher baseline FEV-1 having an easier time initially, and most patients reporting overall improvements in their FEV-1 and overall condition within the first few weeks of treatment. This drug is a huge breakthrough for the 508dd, with further improvements coming in the next year for them and the rest of the CF population as mid and late stage clinical trials with 661/770, and the addition of VX 371 and second generation correctors start reporting results in 2016 extending the benefit to most CF mutations and improve results for patients currently on first gen treatment from VRTX.
As a CF parent, you are certainly aware that PFT's deteriorate on 2% yearly average, even with all the palliative CF treatments currently approved before Orkambi . The lumacaftor/ivacafator rollover study has demonstrated durable stability in PFTs and decreased incidence of hospitalization and infection weight gain and reported quality of life assessments compared to being on existing treatments alone two years after initiating treatment. Just one of these criteria needs to be reported to allow renewal of Orkambi at 6 months under Medicaid guidelines issued in the first week of August this year. BTW: CF patients have a legal precedent in demanding insurers to give necessary treatment after the court case in Arkansas challenging that state's medicaid denial of Ivacaftor to qualified CF patients. Those patients are now receiving Kalydeco under their Medicaid insurance and the state had to pay the legal costs for the plaintiff's victory in this case.
Longlivevrtx, one last thought. I hope you child can benefit from these new CFTR modulators. If insurers are giving your health care provider a hard time in starting Orkambi, VRTX is assisting patients and health care providers in getting the necessary authorizations from the insurers. Whatever coure of treatment you choose, I wish you and your child well in battling this disease.
Glad, tt does seem odd he does not acknowledge the benefits proven in Transport and Traffic, the Phase 3 trials that produced statistically significant benefit in over 1000 patients after just 6 months of treatment with Orkambi meeting primary endpoint goals and allowing FDA approval. Only a 4.2% dropout rate was reported in these Phase 3 trials, and on completion of Transport and Traffic, over 1000 patients (greater than 90% of those enrolled in the phase 3 trials) voluntarily have continued in the rollover study including the patients previously on placebo during the Phase 3 trials whose improvements after starting Orkambi in the open label rollover again duplicated the results of the treatment group at 6 months and all patients have had sustained benefit for the past 2 years. Certainly the first few weeks of treatment can be challenging for some of the 508dd patients starting Orkambi, but the pay off after just 6 months is already proven, so renewal of medication for the majority of patients started on Orkambi should not be a problem for the great majority of patients.
Orkambi launch must be tracking well. Looking forward to CF clinical trial data release from VRTX and Pharion at NACF meeting next week and third quarter conference call the week of Oct 26.
More than 15 abstracts related to Vertex's CF development program were accepted for presentation at NACFC. Vertex today provided the following updates to its development program in CF and highlighted select presentations from the conference:
Two Next-Generation Correctors To Enter Clinical Development
Vertex today announced that it is advancing two next-generation correctors from its research program into clinical development. Known as VX-152 and VX-440, these next-generation correctors will be evaluated alone and in combination with VX-661/ivacaftor in Phase 1 studies in healthy volunteers beginning in November 2015. Pending results of these studies, Vertex plans to initiate Phase 2 studies in people with CF evaluating VX-440 or VX-152 in combination with VX-661/ivacaftor in the second half of 2016. The studies of a triple combination (VX-152/VX-661/ivacaftor and VX-440/VX-661/ivacaftor) planned for the second half of 2016 are expected to enroll people with CF who have two copies of the F508del mutation and people who have one copy of the F508del mutation and a second mutation that results in minimal CFTR function. VX-152 and VX-440 are designed to further improve processing and trafficking of the CFTR protein to the cell surface, beyond that observed with a single corrector combined with ivacaftor, which may enable increased CFTR chloride transport, a measure of the function of the CFTR protein at the cell surface.
In human bronchial epithelial (HBE) cells with two copies of the F508del mutation and in HBE cells with one copy of the F508del mutation and one copy of a mutation known to result in minimal CFTR function, the triple combinations (VX-152/VX-661/ivacaftor and VX-440/VX-661/ivacaftor) resulted in chloride transport (percent of normal) that was approximately three-fold greater than the use of the lumacaftor/ivacaftor combination in these cells.
Should have a positive impact on VRTX stock price . Parion drug and new second gen CFTR correctors entering VRTX clinical trials next month should allow VRTX to continue to expand and improve it's CF treatments that address the underlying cause of the disease in 90% of the CF population. Improvements in it's existing treatment with VX661/770 and Parion's 1037 will and will allow it to maintain it's leadership position, and addition of 2nd gen correctors will offer hope for more effective treatment of both 508 homozygotes and heterozygotes.
Preclinical triple combo data measuringCFTR function and cilia beat show major improvements likely in the treatment of 508 dd homozygotes and heterozygotes, especially with the addition of EnAc inhibitors from Parion. Expect co-formulationof the triple drug regimen in a single tablet to ease compliance by reducing pill burden. Automated continuous manufacturing of these drugs by VRTX will make supply of drugs smooth and predictable, and will likely given the increased number of patients to be treated make the cost of these meds actually go down. I suspect the benefit of treatment of the youngest children will be seen in the lack of progression of lung disease (they won't be as sick) eliminating need for treatments 2 hrs daily using nebs, vests, feeding tubes as welll as thetreatments for CF when the disease advances e.g. hospitalizations for recurrent infections and lung transplants. That in the long run will mitigate the overall cost of care for CF over the lifetime of the youngest CF patients.
RBC Capital analyst Michael Yee reiterated an Outperform rating and $145 price target on Vertex Pharma. (NASDAQ: VRTX) saying the stock remains their top idea and they'd be buying here on the pullback.
"Based on channel checks at the NACF conference we're buyers and believe VRTX will post a solid Q3 result. VRTX is executing on multiple fronts: likely good launch of Orkambi, 2 new correctors into the clinic that should be in Phase II as a "triple pill" next year, introducing pipeline they haven't talked about yet, and likely becoming very profitable..."
UBS reiterated a Buy rating and $160.00 price target on Vertex (NASDAQ: VRTX) following the North American Cystic Fibrosis Conference. VRTX presented preclinical data showing enhanced CFTR function with the two triple combo candidates over Orkambi.
Analyst Matthew Roden commented, "We attended the North American Cystic Fibrosis Conference, where Vertex provided an update to their cystic fibrosis (CF) programs. Of note, the company presented preclinical data showing enhanced CFTR function with the two triple combo candidates over Orkambi. In addition, they highlighted early data showing the benefit of combining Orkambi with ENaC blocker VX-371 (P-1037). Although the focus of the meeting was understandably on CF, management plans to discuss programs outside CF on the 3Q call and at a competitor conference in January. We continue to expect VRTX shares to be a good performer in the fall and into 2016 with what could be an explosive launch, a turn to profitability in 4Q, and several catalysts in 2016
GLPG data is based on it's own HBE assay to test it's triple combo for 508DD homozygotes, and comparing it to Orkambi pre-clinical data published by VRTX. VRTX says it's own triple combo will be tested with VX 661/770 and one of the two selected second gen correctors noted below in the press release from VRTX last week at the NACFC. (Note that VRTX triple combination treatment has demonstrated a three fold improvement in the company's own HBE assay in cells from 'het-min' CF patients who are 508D heterozygotes for which no treatment is yet available. The six fold increase cited by GLPG is not specified to be in the het min 508 heterozygotes (which are harder to treat) and is reported using it's own HBE assay and comparing it to results from separate HBE studies done by VRTX presumably on 508dd homozygotes. Not comparing the effects of Orkambi using the same HBE assay in a double blinded study in the same mutations makes comparisons between the two drugs impossible in terms of clinical superiority.
From VRTX press release at NACFC meeting last week:
"In human bronchial epithelial (HBE) cells with two copies of the F508del mutation and in HBE cells with one copy of the F508del mutation and one copy of a mutation known to result in minimal CFTR function, the triple combinations (VX-152/VX-661/ivacaftor and VX-440/VX-661/ivacaftor) resulted in chloride transport (percent of normal) that was approximately three-fold greater than the use of the lumacaftor/ivacaftor combination in these cells. A significant increase in cilia beat frequency was also observed with triple combination therapy as compared to the use of the lumacaftor/ivacaftor combination in these cells. These in vitro data suggest that a triple combination of a next-generation corrector with VX-661/ivacaftor may improve CFTR function in cells with two copies of the F508del mutation and cells with one copy of the F508del mutation and one copy of a mutation known to result in minimal CFTR function.
Harvey, I agree that VRTX will remain a long term winner in the CF space because it's 'quad' treatment will own the space with very few CF patients left, who are not already benefiting from VRTX treatments. The limited ability for potential competitors to recruit treatment naïve CF patients for advanced stage clinical trials since the great majority of CF patients will already be benefiting from on effective VRTX treatments and not want to risk worsening their clinical condition by experimenting with untested/unapproved alternatives. This will create high hurdles for potential competitors like GLPG and CNCE to overcome because their CF drugs will not likely offer significant incremental clinical advantages in safety and efficacy (as opposed to theoretical test tube benefits they are claiming in test tube assays ). And the potential for VRTX in it's pipeline of non CF drug candidates in influenza, oncology, neurologic disease (spinal cord injury, chronic MS and Huntington's) and in the treatment of genetic diseases with gene editing technologies (yet to be announced) under CSO David Altshuler's leadership will represent growth prospects for VRTX not yet taken into account by Wall Street analysts.