MPNforum Magazine

Jakafi has changed everything.  Except the price.

 In a small French laboratory, a scientist working with only three patients, followed his hunch that events in the heart of the cell’s nucleus were behind polycythemia vera. His hunch paid off and turned the MPN world upside down. 

 In the Spring of 2005, Dr. William Vainchenker’s discovery that PV was related to a sub-atomic mutation in the JAK2 gene on chromosome 9  was corroborated by three other independent groups taking different research directions.

 Thus was born the JAK2 mutation revelation and the start of a race to find a small molecule that would inhibit its biological activity. It was a race won by Incyte Corporation in  2011 while the rest of the field to this day is still on the backstretch struggling to the finish line.

 The resulting development and marketing of ruxolitinib (Jakafi) by Incyte offered new hope to MPN patients and has dominated the pharmaceutical industry’s MPN R&D work. Today, myeloproliferative neoplasms–  this tiny MPN backwater of blood disease —  has moved center stage in hematology, attracting billions of dollars in investment capital, changing the outlook for patients and caregivers alike. 

Not only are the JAK2 inhibitors likely to fill the MPN drug formulary for years, these mysterious  molecules — working in still largely inexplicable ways — are the launchpad for drugs impacting major unrelated diseases.

 The findings in Vainchenker’s quiet little lab (INSERM U1009) at the Gustave Roussy Institute, Rue Camille Desmoulins, Villejuif, created a drug revolution bringing enormous relief to patients…at a heavy price.

 Jakafi — is it effective?
Myelofibrosis is like the Black Queen on the MPN chess board…powerful and capable of slashing destruction.  It can also just sit there behind a  wall of pawns and do very little. It all depends on development, progression of the game. Jakafi is like the White Knight that suddenly appears on the board.  In the right hands and at the right point in the game, the Knight is able to limit and control the Queen’s moves.

The myelofibrosis world without Jakafi lacked an adequate defense against the Queen.  Jakafi made that big a difference in our MF lives.  There were drugs but none able to reliably control splenomegaly or constitutional symptoms.  The arrival of Jakafi made treatment of MF a whole new game.

But is it cost effective?

It’s never a comfortable exercise to establish the cost effective price of a drug based on some arbitrary value of a human life-year.  Still, in the real world those decisions are made all the time. The UK’s healthcare oversight commission, NICE, recently declined to recommend use of Jakavi in the National Health Service based on just such considerations.

Exploring the potential for greater survival as a result of Jakafi therapy, Dr Srdan Verstovsek of MD Anderson, the principal investigator of ruxolitinib and heavily published author of scientific papers on Jakafi, presented a paper at ASH on the long-term followup of 107 MF patients.

Dr. Andrea Messori, (ESTAV Centro Toscana and University of Firenze)  produced a lifetime survival analysis of Dr Verstovsek’s data, published in Blood.  He concluded ruxolitinib provided a “lifetime survival gain of 5.4 months per patient.”  Using a cost-effectiveness threshold of 60,000 euros per life year gained, these 5.4 months of increased survival have an economic value of 27,000 euros, the equivalent to a cost of 0.9 euros per mg. of Jakafi.

Messori noted, based on mean dosage and current pricing, the cost of Jakafi is actually 3.5 euros per mg or more than three times higher than the cost-effective price.  And that’s if Jakafi is indeed capable of life extension.

Life extension, booming sales

Dr. Verstovsek’s preliminary findings of life extension – mainly a statistical presumption based on review of trial data —  could be part of the reason for Incyte’s stronger than anticipated earnings and upgraded projection of revenues this year to $225 million. 

Offering life extension benefits extends Jakafi’s application to less symptomatic patients.  Considering the common sense conclusion that reduction of swollen spleen permits greater mobility, increased appetite and thus a higher quality of life, these retrospective findings of life extension are not surprising.  

The longevity benefit – along with preliminary indications of possible fibrosis reversal after continued extended Jakafi therapy – are, however, far from confirmed. Dr. Verstovsek himself in presenting these data questions the methodology and conclusions based on historic and unmatched control samples.  The so-called rebound effect – the pronounced resumption of intensified MF symptoms upon sudden interruption of Jakafi therapy — seems to confirm that the underlying MF disease is not affected by the relief of symptoms.

A blockbuster drug, nevertheless

Jakafi’s market acceptance will only expand based on these very early indications of possible  bone marrow fibrosis reversal and the likely FDA approval of Jakafi for PV patients after completion of the current Phase III clinical trials this year.. It seems clear Jakafi is on track to become a blockbuster billion dollar drug,  Incyte’s partner, Novartis, with over 3000 Jakavi patients in Europe already, confidently predicts a billion dollar market on the Continent.

All in all, not a bad performance for Incyte, an old California genomic database company that just entered the drug development business a few years ago.

So is it time to lower the price?

Given all this good news, high profits, booming sales and good prospects… maybe it’s time for Incyte to lower the price of Jakafi.

MPN patients have several drugs to choose from. Intermediate and high-risk MF patients have few options. And the interferons are generally considered effective only at early stages of symptomatic myelofibrosis. Incyte has a temporary monopoly on the most effective drug to treat MF.  By comparison, the most common drugs used to relieve MPN symptoms and prevent thrombosis have radically different price points…with Jakafi towering at the top of the heap. .

 Drug                                                              Estimated Annual Cost ($)

Bayer Aspirin, 100: 81mg,                                                     33.85

Hydroxyurea   30:  500mg capsules                                      298.00

Peg Interferon alpha-2b  (120MCG)                                      20,000 – 41,964

Pegasys                                                                                40,000 – 42,000

Jakafi  (dosage tolerance-limited)                                         56,000 – 84,000

• ·     *Source http://rxusa.com/cgi-bin2/db/db.cgi and B&B Pharmacy, Asheville, NC.

What Incyte did to bring Jakafi to market

Incyte took the multimillion dollar do-or-die risk of betting on ruxolitinib. As did several hundred MF patients. Over several years through international trials ruxo made its way through the approval process. It was never a sure thing that, in the end, an effective med would finally emerge, approved by FDA, to provide symptomatic relief to MF patients.

Paul Friedman:  MPN patients are part of a grand plan to roll out JAK inhibitors.

Before Jakafi was approved, MPNforum asked Incyte CEO Dr. Paul Friedman, why us, why put all this money and effort behind a drug to relieve symptoms of a disease affecting a small population with a rare blood disease?

Friedman: Well there are a lot of diseases where a JAK inhibitor can work. MF frankly, we thought would be the quickest path to a first approval and that has turned out to be the case although we’re not approved yet. I don’t want to put the cart before the horse. But for something like rheumatoid arthritis where these drugs work dramatically well there’s a much longer development path, an order of magnitude more patients who have to be studied and approved therapies. We looked at diseases where we thought shutting down JAK signaling would have therapeutic benefit. There’s a list and MF is on the list and we’ll get fairly dramatic results.

So we thought there were multiple therapeutic areas into which you could go and MF is just one of them and one we felt there was an obvious unfulfilled therapeutic need. And we thought we could develop the drug the quickest So that’s kind of why we went into it.

And the payoff?

Friedman was prophetic.  In the second quarter of this year, Incyte revenues surged 17.5% to $101.7  million.  A big chunk of that is licensing and royalty fees but Jakafi sales of $54 million + in the quarter were up 82% over last year.

And those other therapeutic areas Friedman was talking about?  Novartis is in a Phase III RESPONSE clinical trial testing Jakafi on PV and Roche has a Phase II trial in process combining Jakafi with its own Xeloda for metastatic pancreatic cancer.  And rheumatoid arthritis?  Incyte and Eli Lilly are wrapping up a Phase III trial of baracitinib, another JAK inhibitor for treatment of RA and other inflammatory and autoimmune diseases.

For the full year, Incyte is now expecting sales of a quarter billion dollars plus royalities from Novartis on Jakavi sales. And sits on a product pipeline swollen with promising offshoots of Jakafi.

So should Incyte’s shareholders and partners be happy?  Thanks to Jakafi, they should be chuckling all the way to the bank. Before Jakafi was approved for sale Incyte was selling below $12/share. Today’s quote is over $27

And what about that other Jakafi stakeholder:  MF patients?

Jakafi has been an unquestioned blessing for MF patients.  Many MF patients got the option to regain a reasonable quality of life, to find relief from pain, to recover from weakness.  The drug has not worked for everyone.  Some suffered and died in clinical trial.  Some suffered after interruption of therapy.  And for those for whom it has worked it hasn’t always continued to be effective. There are serious side effects, some of which can be managed, some can’t.   But Jakafi is an option where before there was none.

Jakafi offered us an alternative to splenomegaly or risky stem cell transplant. However, there’s is a dark side to this option. Since Jakafi doesn’t affect the natural course of the disease but may control the worst of MF symptoms, an early MF patient can easily slip into high-risk MF or progress to AML or grow too anemic or thrombocytopenic for a SCT during the course of the therapy.

And an even more fundamental consequence affecting all MPN patients: The very success of Jakafi in the marketplace has drawn research investment dollars into the JAK inhibitor pool, funding lookalike compounds instead of seeking the source and cure of MPNs.

Incyte’s out-sized footprint

Incyte’s dominating influence over the MPN research conversation is powered by its investment, with its partner Novartis, in the long and successful trials leading through COMFORT I and II.  Dozens of medical research and teaching facilities in the United States and Europe and the work of leading hematology clinical investigators have been heavily supported by Incyte in its large scale effort to bring Jakafi to market. 

As a result, both those presenting Jakafi scientific findings and those reviewing and reporting on those presentations alike have received funding from Incyte. Through outright grants, honoraria, travel perks, consulting positions, and other inducements, Incyte has helped create a compromised environment. The Incyte influence extends beyond the medical arena.  In support of Jakafi marketing, Incyte contributes to MPN non-profits as well as MPN commercial service companies until there are few MPN voices independent of this drug company’s influence.

Incyte Cares

Incyte has set up a special website to help patients access Jakafi and get co-pay reimbursements.  It’s a sensible move since few humans can pay $7000 a month for a drug and reluctant insurers will only grow increasingly resistant.  But to demonstrate that Incyte cares about patients – patients who helped pave the way for this billion dollar drug –  perhaps a direct and substantial price cut would be more convincing.

Reasons to lower the price of Jakafi…

In these unsettled economic times, with medical insurance and access to medical care undergoing radical revision, fielding a life-saving drug at a price that is demonstrably not cost effective is a strategy clearly in need of review.  Severely stressed national budgets and anticipated reluctance of insurance companies to cover Jakafi automatically suggests some adjustment is in order.  Besides, it’s the right thing to do. Incyte took the risks and is entitled to the rewards. But Jakafi is not the product of a single team in a single company but includes Dr. Vainchenker and his associates in VilleJuif, William Dameshek, independent MF and genomic researchers, taxpayers funding the Human Genome Project, and mostly  MF patients, some of whom are frozen out of the benefits of Jakafi by its price.

Incyte’s monopoly over MF JAK2 inhibitors is coming to an end, With shareholder return on investment assured and both sales and profits rising, this may well be the time to broaden access to Jakafi through price adjustment .The effect might even be felt across the Atlantic and help Novartis to reverse the NICE decision and relieve English MF patients reliant on the National Health Service.

Mostly, why not lower the price simply because Incyte cares?

— Zhenya Senyak

Incyte Corporation response

Incyte is science-driven and patient-focused.  We believe in operating openly, honestly and with the highest degree of ethics and integrity. This includes making sure that we comply with all applicable laws and regulations globally.  Incyte is committed to patient health and ensuring they have access to Jakafi® (ruxolitinib) despite any financial hardship through its IncyteCARES program. IncyteCARES helps patients receiving Jakafi overcome access and cost barriers through a generous suite of support programs that include free patient assistance to those without insurance, co-pay assistance for patients with private insurance and who will pay no more than $50/month for their Jakafi, and referral support to charitable foundations that can assist patients with their cost share. In addition the program offers education and resources that help patients understand their disease and treatment with Jakafi.
     

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