From an article posted on the Gladstone Institue web site:
Once the scientists discovered this key process, as described in Nature, they began to investigate how the body senses the fragments of HIV’s DNA in the first place, before alerting the enzyme caspase-1 to launch an immune response in the CD4 T cells. To identify the so-called DNA sensor, the scientists found a way to genetically manipulate CD4 T cells in spleen and tonsil tissue. In doing so, they discovered that reducing the activity of a protein known as IFI16 inhibited pyroptosis, explained Zhiyuan Yang, PhD, a Gladstone postdoctoral fellow who is one of the paper’s two lead authors.
“This identified IFI16 as the DNA sensor, which then sends signals to caspase-1 and triggers pyroptosis,” says Kathryn M. Monroe, PhD, the Science paper’s other lead author, who completed the research while a postdoctoral fellow at Gladstone. “We can’t block a process until we understand all of its steps—so this discovery is critical to devising ways to inhibit the body’s own destructive response to HIV. We have high hopes for the upcoming clinical trial.”
The Phase 2 trial—which will test an existing anti-inflammatory’s ability to block inflammation and pyroptosis in HIV-infected people—promises to validate a variety of expected advantages to this therapy. For example, by targeting the human body, or host, instead of the virus, the drug is likely to avoid the rapid emergence of drug resistance that often plagues the use of ARVs. The anti-inflammatory may also provide a bridge therapy for the millions without access to ARVs, while also reducing persistent inflammation in HIV-infected people already on ARVs. Many suspect this inflammation drives the early onset of aging-related conditions such as dementia and cardiovascular disease. By reducing inflammation, the drug might also prevent expansion of a reservoir of latent virus that hides in the body where it thwarts a cure for HIV/AIDS
Here's the opinion of the biotech analyst from JP Morgan from an interview on May 15, 2014:
GM: We also like Vertex Pharmaceuticals Inc. (VRTX:NASDAQ)—a much smaller large cap than Gilead. This name has caused worry in the current biotech equity environment, with the recent shift in sentiment. I think a lot of investors are unwilling to take on a binary event in this environment—the appetite for that is very low now.
Vertex has two Phase 3 trials, called TRAFFIC and TRANSPORT, for a form of CF where patients are homozygous (have the same gene from both parents) for a mutation called delta F508. The data are due out literally any day now, with the latest date in July of this year. Some investors say this trial could fail. Well, yes, that’s true. I would say that the probability of the combination of Kalydeco (ivacaftor) + the experimental drug VX-809 (lumacaftor) not showing any signal of activity at all is less than 5%. Three different Phase 2 trials prove that Kalydeco plus a corrector, whether it’s VX-661 or VX-809, is efficacious. That’s why we like the risk/reward on Vertex at these current levels.
The major risk is currently out of the stock after the 'binary event' . Those who sold their shares on the advise of Geoff Porges before the release of the binary event TRAFFIC/TRANSPORT data last Tuesday have sellers remorse. Those who bought expensive put options or shorted Vertex before Tuesday lost a bundle. Those who bought shares this past week and have some patience will IMO at least double their money over the next 18 to 24 months. Currently, it's relatively safe to be long Vertex and not worry too much about day to day price fluctuations. Each positive data release on 770 monotherapy and 661/770 and 809/770 ongoing trials, as well as news about the initiation of addition clinical trials for both CF second gen correctors and non CF assets, and news of sNDA filing and NDA filings for 770 and 809 will bring increasing price per share going forward from now until 809/770 receives approval next year. Then the market will reward the stock on a ten fold increase in revenue over the next two years. Enjoy the ride.
The cost of drug research is not unique to Vertex. It is largely mandated by the federal law enforced by the FDA. The difference between the Vertex of 15 years ago (the time of the publication of Werth's first book prior to the approval of any Vertex drug) and now is like night and day. Business people are at the helm of the company and are prioritizing development resources which has resulted in financial stability of the company, Look at the street's analyst's average revenue and eps projections for VRTX in 2015 and you can see the science is finally going to generate a sustained profit with 809/770 being approved by the FDA. The R&D focus of the company will continue to be pursued with a reasonable allocation of the company's assets to allow for future growth. The initial vision of the founder will finally be realized but within the context of responsible financial stewardship for shareholders, That is why the stock is quite stable at the current stock price, and with each press release detailing further progress in the approval process for it's pipeline assets, the share price is only likely to rise further given the growth potential of these breakthrough treatments.
Hopefully clinical trials using VX 765 treating HIV infected patients will be announced this summer. I think Jeff Chodakewitz (an authority on HIV) being hired as CMO at Vertex at the time Warner Green published his work testing VX 765 in HIV infected human tissue was no coincidence. Now that thephase 3 809/770 CF data has been released, and is positive, Vertex will likely start advancing some of it's non-CF R&D pipeline assets as well, and VX 765 is certainly advanced far enough from a safety standpoint in humans to resume it's testing in this new potentially breakthrough clinical application. Warner Green said in interviews last December that Vertex was negotiating with his Gladstone Institute at UCSF to start clinical trials and estimated those trials could start in a matter of months. That suggests an announcement for those clinical trials may be announced very soon.
Drs. Leiden, Chodakewitz, Boger and the Vertex scientific advisory committee will recruit someone comparable to Peter Mueller to lead the Vertex R&D program. I suspect they will have an easy time finding such a candidate given the growth trajectory and revenue stream Vertex is now expecting with the approval of 809/0770 just months away and a pipeline of preclinical drug candidates for cancer, neurologic disease, autoimmune disease as well as second generation correctors for CF. Their experience and contacts in the pharmaceutical and academic research worlds will certainly give them plenty of candidates to consider for the position. At this time, Vertex is a great career move for the right person wanting to lead the growth of the R&D arm of this growing company.
Boomer Esiason is a major fund raiser for the CFF. Listen to the above interview but especially the 6:00 to 6:30 minute mark in this interview, where Boomer answers the question "do you expect a cure?" He talks about the amazing beneficial effects his 23 yo son, Gunnar, who has CF, is experiencing on a study drug with results of study soon to be released. Sounds like VX 809/770 to me, which is going to have a profound effect on CF patients. Its going to allow patients like Gunnar Esiason the chance to outlive their parents.
The calls from certain members of Congress to explain high drug prices has no teeth in terms of laws. Both Gilead and Vertex continue to get their negotiated current rates for their breakthrough drugs world wide, often with discounts. Regulation on pricing would stopfurther drug research and development unless they eliminated the legally required and extremely costly regulatory development process which will never happen. If there is no reward for the high costs of development and the high risk of failure and potential competition, there would be no advances in treatments for these dreadful diseases by the pharm industry. Society eventually gets the opportunity to get the drugs at a severe discount after the patents expire and the drugs are generic (80% of all drugs sold in the US are now generic). In the meantime the investors who take all the financial risk for new drug development are entitled to the reward if they succeed after the average wait of 10 to 15 years in takes in the US from pre-clinical testing to approval. It's a high risk, but high reward investment, The investment process is part of capitalism. It is the reason HIV, Cancer, hep C and diseases like CF have finally received breakthroughs in treatment and patients are benefiting, along with those investors who took the financial risk . Also remember, government taxes the profits made on these drugs both from the drug companies and it's investors and employees, and thereby benefits as well from the tax revenues and the productivity of patients who are now able to work instead of being ill and disabled by their disease when these drugs are approved and getting prescribed.
It's probably not unreasonable to wonder if the lack of any public discussion by Vertex management about their plans for their development of the non CF drug pipeline assets is a 'lack of any enthusiasm on the part of VRTX management' for the application of VX 765 to treat HIV. But sometimes you need to read between the lines of what has transpired since December's announcement by Warner Greene's lab and their discovery of the effect of VX 765 on HIV infected tissues in vitro. Vertex announced it had hired in early January 2014, Jeffrey Chadakewitz as it's new CMO. His expertise and academic career at Yale and subsequently at Merck was devoted in large part to trying to develop a cure for HIV infection. The timing of his hiring at Vertex is hardly a coincidence and represents anything but a lack of enthusiasm on the part of VRTX management for the development of VX 765 to treat HIV. The only reason it has not yet been discussed publicly by VRTX management IMO, is that management does not want to distract Wall Street from the focus Jeff Leiden has made to the company's commitment to CF. The need to timely execute the NDA submission of 809/770 is a business priority to monetize the company sufficiently to allow it to self finance the development of it's earlier stage non CF assets. I suspect if no mention of VX 765's application to HIV is made by management on this coming Thursday's May 1. 2014 first quarter conference call, it will certainly be announced sometime soon following the release of the clinical trial data from TRAFFIC and TRANSPORT. And this will likely raise the price of the stock and any theoretical projected value of any Vertex buyout offer by a larger drug company. VX 765 could be worth more than all the CF drugs combined.
Six separate postings just listed recruiting for in house corporate counsel to support launch of new orphan drug in separate international markets: Here's one example in Germany:
Functional Area: General Business / Operations
Seeking in-house attorney to provide legal support for the international operations of a US-based pharmaceutical organization.
Duties include advising Country Managers and functional teams on EU and national law matters, advertising and promotion of pharmaceuticals, contracting, competition law, data privacy, transparency, supply and distribution and compliance with internal policies and applicable regulations and industry codes.
The company has recently set up commercial operations in countries, including Germany, France, UK, Spain, Italy and Australia. Candidates must demonstrate ability to manage multiple clients and provide clear advice in a fast paced work environment.
The successful candidate will upon hire be supporting one or more regions with all commercial legal matters. Excellent communication skills, good judgment, ability to work independently, and strong business acumen are essential. The role will report to the Legal Director, International in Switzerland, but can be based in any of the European offices. Travel is required (approximately 25%) mainly in Europe
European Law Degree
Previous professional experience
Experience in a life sciences or pharmaceutical company, preferably supporting an orphan drug
Good knowledge of commercial law and competition law
Experience with privacy and regulatory issues
More likely JNJ would buy out DXCM, since it's finger stick blood testing franchise is threatened by this technology and it's insulin pump sensing capability is being co-developed with DXCM.
Phase 3 study to be started which would allow 3000 more patients to be approved to use kalydeco monotherapy.
The facts are that preclinical tests in theoretical competitors are years away from proving efficacy and safety. The facts are that since 809/770 has sustained benefit in slowing the loss of lung function in 508dd XF patients, it is the first and only approvable treatment that can make an impact on prolonging life in this otherwise fatal disease. In younger patients, it will prevents progression of irreversible lung damage. Sure competition is on the horizon, and the most advanced competitor is coming from Vertex itself, in the form of VX 661 and second gen competitors already in, or about to enter clinical trials (not preclinical testing years behind Vertex). Vertex owns this space for the next few years and long term, (after telaprevir's rise and fall) VRTX will certainly be aggressive in developing and/or acquiring next generation treatments to improve outcomes and expand the CF treatment population. .
Final raw data from TRAFFIC and TRANSPORT has been in for two weeks. Why would just this week, Vertex management start to recruit experienced in house counsel to establish the marketing of a new orphan drug in six countries around the world, if the raw data available for their review did not support the hiring of such highly paid professionals to establish a successful commercial launch. Wouldn't one wait to hire such expensive professionals until one was certain of their imminent need?
Key Account Manager - NWS & QLD
Functional Area: General Business / Operations
Vertex Pharmaceuticals Inc. is seeking a Therapeutic
Specialist (Key Account Manager) to be a part of the exciting launch effort of an innovative
breakthrough treatment for Cystic Fibrosis (CF). The Therapeutic Specialist
will be responsible for ensuring that all barriers to usage of this new orphan
product are addressed and that all patients who could benefit from the product
have access to it. This goal will be achieved by the development and execution
of specific account level business plans at all CF centers; communicating
disease and product knowledge to healthcare professional customers and ensuring
that the full long term value of the product is fully understood by all
relevant stakeholders This elite individual must thrive in a fast-paced, highly
collaborative environment, drive for results, understand market dynamics,
demonstrate excellent judgment, and be motivated by the desire to improve
patients' lives. The ability to see the world through the eyes of the varied
customers and stakeholders with which this role will interact will be a
necessary and differentiating quality.
Needham & Company analyst Alan Carr weighed in on Vertex (NASDAQ: VRTX) following top-line results from a Phase 2 trial of ivacaftor in cystic fibrosis patients with residual function CFTR mutations.
"We note statistically significant, but modest absolute changes in FEV1 in the two-part trial (2.8% vs. 0.6% placebo [p=0.004] in 2-wk blinded Part 1 and 4.7% [p=0.0001] in 8-wk open-label Part 2)," Carr said. "Based on these results, the company plans to move forward with a Phase 3 trial after discussions with regulators around trial design. Results from the pivotal TRAFFIC and TRANSPORT trials are expected soon. These trials are testing ivacaftor/lumacaftor in homozygous F508del pts and are at the core of the company's CF strategy. We continue to expect a positive outcome and reiterate our BUY rating and $95 target."
Vertex Pharmaceuticals Incorporated is looking to hire a Senior Director to join the Global Talent Acquisition Team in Boston, MA. The Senior Director, Global Talent Acquisition will provide strategic and operational leadership to Vertex as the company continues its rapid growth. With their business mindset this HR leader will bring a proactive planning focus to Talent Acquisition at Vertex. He/she will focus on Talent Acquisition Operations, the quality of candidates to ensure they fit not only technically but culturally and to drive workforce planning.
Consider the possibilities: At a minimum the above article suggests the possibility of using VX 765 in every HIV infected patient. VX 765 would prevent the the infected patient's self destruction of it's own CD4 T cells that seems to naturally occur in response to HIV infection. Furthermore, it would prevent the emergence of resistance to ARV drugs, and thereby enhance the effects of ARV therapy. Lastly, it may prevent the inflammatory complications of long term ARV therapy which include premature aging and death due to heart disease and dementia. This would be an incredible step forward in the treatment of HIV worldwide. Another first to market opportunity for Vertex with incredible benefit to a large and suffering population worldwide.. It could reduce health care costs overall by preventing the emergence of HIV resistance requiring changes in ARV treatment, prevent the development and need for treatment of the long term complications of ARV drugs (heart disease and dementia) and could be part of a treatment that actually eradicates the latent HIV reservoir in patients being treated for a potential cure for HIV infection.
Papa ... I think you mean VX 787 and VX 509 have not been partnered yet. I would not assume they are 'dead' I would rather describe their status as 'dormant'. They could still be developed internally .once VX 809/770 is approved and cash flow at VRTX permits expanding the R&D budget to further develop their potential. Likewise no mention of VX 765.for the treatment of HIV. Management at VRTX wants the focus of Wall Street to be strictly on CF;, and I agree that VX 809 Phase 3 studies will be positive and that will be the catalyst for the stock move to new highs, and the trigger to announce the development of the non CF assets in the VRTX pipeline.