Patients Report Barriers to Getting Afrezza, but A1C Results Are Worth It

In January 2016, an endocrinologist told his new patient that MannKind Corporation was “going out of business,” before he rambled on about having shorted the stock. The doctor said he didn’t want to write a prior authorization (PA) letter for Afrezza because it might damage his reputation with the insurer.

But the patient, Hillard Saveth, didn’t give up. As he relayed in an e-mail to Evidence-Based Diabetes Management (EBDM), Saveth had obtained Afrezza through his former primary care physician (PCP) before a policy change by his pharmacy benefit manager sent him looking for a “letter of medical necessity.” With Afrezza, he’d attained glycated hemoglobin (A1C) levels of 5.7%, his lowest ever. As a person with type 2 diabetes (T2D) and an aversion to needles, Saveth saw Afrezza as a godsend, and he was determined to continue.

By May, the endocrinologist had changed his mind on the fast-acting, prandial inhaled insulin. In the meantime, Saveth spent money out of pocket to stay on Afrezza and keep his A1C at 5.7%. During this period, Saveth even asked for a letter that said he could get Afrezza if he switched to metformin and experienced side effects. He never filled the prescription for metformin that his endocrinologist recommended.

“The long and short of it is, you need to have a plan,” Saveth said.

Saveth was one of several people who shared with EBDM their stories of trying to gain access to Afrezza, which the FDA approved in June 2014 to treat both T2D and type 1 diabetes (T1D), the latter in combination with a long-acting basal insulin.¹ When EBDM asked patients like Saveth to discuss problems with payer coverage, they volunteered stories about doctors reluctant to prescribe the drug, nurses who championed their cause, and a marketing decision by Sanofi that 1 patient found hard to fathom—and that MannKind is still working to undo.

Afrezza’s odyssey, both before and after FDA approval, seems like something from a novel. On one side sits a small core of devoted patients; on the other, there’s an equally active band of analysts who watch MannKind’s every move, tracking its cash position and Afrezza’s weekly script count. Through MannKind’s severed marketing relationship with Sanofi to Afrezza’s closely watched relaunch, one of the drug’s bright spots has been patient reports on social media, often complete with documentation of “lowest ever” A1C levels.^2-4

MannKind’s fortunes could rise or fall based on decisions by formulary managers who, so far, have put Afrezza outside the preferred tier in Tier 3, reserved for higher-cost branded drugs. Not only do physicians have to order spirometry tests to weed out patients with underlying lung problems (an FDA requirement),¹ but they also must navigate the PA process. Depending on the plan, some patients may not be able to get Afrezza through a PCP, only an endocrinologist. Patients also report having to justify why they haven’t tried older therapies first.

Michael Castagna, MannKind’s chief commercial officer, told EBDM in an interview that it’s frustrating to see a product that is “completely differentiated” from other insulins being treated like an injected product; he said it’s also frustrating that there’s been no recognition that Afrezza has not taken a price increase in 2 years while other insulins have. (Patients who spoke with EBDM reported paying between $180 and $300 out of pocket for Afrezza; a check of GoodRx in early September showed pricing between $272 and $300.)⁵

Among commercial plans, Castagna said, “we have 71% national coverage.” In Medicare, restrictions are still severe, but where coverage exists, he said 50% of the PAs go through.

This fall, Castagna embarks on the toughest of tasks: a second chance to make a first impression. He and his team must reintroduce Afrezza to patients, payers, and endocrinologists in the wake of Sanofi’s unsuccessful launch, which was abandoned in January 2016.⁴ MannKind has made new hires, is revamping its speaker program, and will concentrate on endocrinologists, not PCPs. MannKind does have some new tools: evidence presented this summer at the 76th Scientific Sessions of the American Diabetes Association (ADA) shows the drug works much faster than other insulins and leaves the body quickly relative to its rivals. It acts in 16 to 21 minutes compared with 45 to 52 minutes for insulin lispro, and its duration of action was shorter by 2 to 3 hours.⁶

The company plans an updated label,⁷ and it has announced a collaboration with JDRF (formerly the Juvenile Diabetes Research Foundation) to make the drug available in the pediatric population.⁸ But there have been setbacks, too: a snag with changing National Drug Codes delayed Medicaid and Medicare reimbursements in August.⁹

The inhaled insulin powder, which comes in color-coded cartridges of 4-, 8- or 12-units to allow patients to customize doses inside the purple-and-white inhaler (SEE FIGURE), will come in a revamped cartridge pack ideal for patients still learning to titrate the product (see Commentary SP473). Recognizing its reimbursement and out-of-pocket challenges, MannKind has reworked its co-pay card so that patients with commercial coverage can keep their costs to as little as $15 a month.⁷ In the interview, Castagna said the company is also working on a fixed cash price.

Still, the contrast between the advocates and the analysts is stark: on August 30, 2016, diaTribe said the advocacy foundation was “very enthusiastic about Afrezza’s potential for people with diabetes in need of alternatives to traditional insulin, and [we] hope very much that patients will be able to obtain access.”⁷

On September 2, 2016, Seeking Alpha’s Spencer Osbourne wrote, “From a pure investment perspective, the street does not care if Afrezza works or not, nor does it care to give a period of time for MannKind to ‘warm up’ into its new role. The street cares about whether there is investment potential in this equity or not.”¹⁰

Where’s the Inhaler?

Kevin Michelizzi thought there must be some mistake. His doctor gave him some Afrezza samples from Sanofi. In an interview, Michelizzi described opening the first box, then a second, then a third. The cartridges were there, but “none of them had an inhaler.” Michelizzi, who has T1D, thought this was absurd and later contacted MannKind to ask, “Are you guys going to fix that?”

Why did Sanofi separate the cartridges from the inhaler? One answer said it had to do with refrigeration, while other reports said it had to do with giving sales representatives a reason to make repeat calls on physicians.

Sanofi spokeswoman Anna Robinson first replied in an e-mail, “All Afrezza samples included 2 pieces—an inhaler and a box of cartridges. In the rare instance when just cartridges were received, Sanofi ensured that the physician was reminded to provide both pieces when sampling and would deliver a sample inhaler to the respective physician if necessary.” In a follow-up e-mail, Robinson said that the cartridges required refrigeration, while the inhalers did not, so this strategy saved refrigeration space.

“We’re stuck with that decision for the next few months,” said Castagna, who reluctantly confirmed the sample configuration. MannKind is retrofitting the manufacturing process so the sample will be in a single box by November, he said.

Overcoming Resistance

By the time of the sample incident, Michelizzi had many concerns about the way the rollout had been managed. He was having tremendous success with Afrezza, but his own experience and his encounters with doctors suggested the word was not getting out. Just to use the product, he’d overcome resistance from his endocrinologist’s nurse, who gave him a spirometry test and told him he didn’t pass. Michelizzi knew he didn’t have bronchitis, so he brought the results to his own nurse practitioner, who said he definitely was a candidate. Then, she went to battle with Michelizzi’s insurance company—who went through 20 years of his medical history. The payer considered the drug “experimental.”

The nurse practitioner pushed back harder. As with Saveth, Michelizzi paid out of pocket at first, which helped his nurse make his case when his blood sugar improved. Michelizzi had a medical reason to use Afrezza—as a long-term type 1 diabetic, he had absorption problems that were being addressed with this new product. In a matter of months, his A1C dropped from 8.1% to 6.0%.

Michelizzi still believes Afrezza can be a success if physicians are properly educated. He feels so strongly that he bought stock in the company. “I’m definitely a guy that’s on board. I’ve had exceptional results.” He’s made one more change, too. He has a new endocrinologist.

For Saveth, resistance gave way to belief, too. By the time he needed his letter of medical necessity in May, his endocrinologist “couldn’t have been more helpful.” When Saveth spoke with EBDM this summer, he had just received a call that his prescription was covered.

Working With the Evidence

If you had to find a patient and a doctor well-equipped to craft an appeal letter, it would be hard to top Mike Hoskins and George Grunberger, MD, FACP, FACE.

Hoskins is a journalist for DiabetesMine who has lived with T1D for more than 30 years, and Grunberger is the past president of the American Association of Clinical Endocrinologists. When Hoskins decided this spring it was time to switch off his insulin pump and go back to injections, he thought Afrezza was worth investigating. “I’d heard some good things in the community,” he told EBDM.

Hoskins obtained samples in May and gave Afrezza a try. By June, he knew he wanted to use it, but his HMO, which is part of Blue Cross Blue Shield of Michigan (BCBSM), initially denied coverage. BCBSM said Hoskins hadn’t done step therapy—meaning he had not tried and failed on other insulins.

A statement from Hoskins’ insurer to EBDM spells out the requirement. “Many of our Blue Cross Blue Shield of Michigan and Blue Care Network plans cover (Afrezza) for type 1 and type 2 diabetes. The criteria: when there is a treatment failure of, or intolerance to, at least 3 months of therapy with subcutaneous rapid-acting insulin (such as Novolog). Physicians are asked to provide information as to why the inhaled product is expected to work when the subcutaneous product did not. Members do not have to see an endocrinologist.”

The statement also says the insurer makes changes based on new evidence, but none are planned.

Hoskins’ timing was fortunate: he had just covered the ADA meeting in New Orleans, so he and Grunberger included information from MannKind’s late-breaking abstracts in the appeal letter. As with Saveth and Michelizzi, his endocrinologist was able to argue the “clinical reality” was that Hoskins had been using Afrezza for the past month. He’d achieved a lower A1C and less glucose variability; thus, he had less risk of ending up in the emergency department. Hoskins said his approval came through “within an hour.”

Afrezza isn’t perfect, Hoskins said, but “when it works, it’s outstanding.” He still uses Novolog at times, and like all those who live with T1D, he’s learned to navigate when using different forms of insulin make sense.

Although Hoskins is pleased his case worked out, he knows that not everyone with diabetes has the same access to information or a physician who is a savvy, well-informed advocate. He knows his $80 co-pay would put Afrezza beyond the reach of others. He also knows from personal experience that many doctors still won’t write the prescription—before he moved to Michigan, his former endocrinologist refused.

It also concerns Hoskins that those making payer coverage decisions about Afrezza—and diabetes, generally—don’t understand the need for people living with the disease to have choices. "They can say, ‘We’re not looking at the money,’” he said, “but they’re only looking at the dollars.”

References

1. FDA approves Afrezza to treat diabetes [press release]. Silver Spring, MD: FDA; June 30, 2014. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm403122.htm. Accessed September 4, 2016.

2. Caffrey MK. Sanofi addresses need for spirometry before physicians can prescribe Afrezza. Am J Manag Care. 2015;21(SP11)SP366.

3. Smith A. MannKind: path to Afrezza survival involves lower prices to woo payers. Am J Manag Care. 2016;22(SP4)SP137.

4. Osbourne S. MannKind: Afrezza scripts, class action suits, Nasdaq listing, insider buys, insurance woes, what investors need to keep in mind. Seeking Alpha website.

http://seekingalpha.com/article/4003058-mannkind-afrezza-scripts-class-actions-suits-nasdaq-listing-insider-buys-insurance-woes. Published August 30, 2016. Accessed September 4, 2016.

5. Afrezza. GoodRx website. http://www.goodrx.com/afrezza?drug-name=afrezza. Accessed September 7, 2016.

6. Baughman RA, Heise, Grant ML, et al. Technosphere insulin inhalation powder (TI) displays earlier onset and shorter duration than insulin lispro (lispro). Diabetes. 2016;65(suppl 1A):100-LB.

7. Marathe P. Afrezza is back with a better co-pay card program and a new cartridge pack. diaTribe website. http://diatribe.org/afrezza-back-better-co-pay-card-program-and-new-cartridge-pack. Published August 30, 2016. Accessed September 4, 2016.

8. MannKind announces collaboration with JDRF [press release]. Valencia, CA: MannKind Corporation; June 10, 2016. http://investors.mannkindcorp.com/releasedetail.cfm?ReleaseID=975283. Accessed September 6, 2016.

9. Update on Medicare/Medicaid coverage. MannKind Corporation website. http://www.mannkindcorp.com/index. htm. Accessed September 1, 2016.

10. Osbourne S. MannKind: 2 months into the relaunch of Afrezza: where things stand and what to expect. Seeking Alpha website. http://seekingalpha.com/article/4003843-mannkind-2-months-relaunch-afrezza-things-stand-expect. Published and accessed September 2, 2016.

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