Radar on Specialty Pharmacy

FDA Approves First Oral Treatment for HAE Attack Prevention

January 12, 2021

When the FDA approved BioCryst Pharmaceuticals, Inc.’s Orladeyo (berotralstat) last month, the drug became the first oral treatment for prophylaxis to prevent hereditary angioedema (HAE) attacks. According to Zitter Insights, payers with nearly three-quarters of covered lives plan to manage it at parity to other prophylactic treatments.

The FDA approved the first drug to treat HAE, Shire plc’s Cinryze (C1 esterase inhibitor [human]), on Oct. 10, 2008. Since then, the FDA has approved eight drugs to treat HAE: half for acute attacks and half for prophylaxis.

By Angela Maas

When the FDA approved BioCryst Pharmaceuticals, Inc.’s Orladeyo (berotralstat) last month, the drug became the first oral treatment for prophylaxis to prevent hereditary angioedema (HAE) attacks. According to Zitter Insights, payers with nearly three-quarters of covered lives plan to manage it at parity to other prophylactic treatments.

The FDA approved the first drug to treat HAE, Shire plc’s Cinryze (C1 esterase inhibitor [human]), on Oct. 10, 2008. Since then, the FDA has approved eight drugs to treat HAE: half for acute attacks and half for prophylaxis.

Orladeyo will compete against Cinryze, Haegarda (C1 esterase inhibitor [human]) and Takhzyro (lanadelumab-flyo) to prevent HAE attacks.

For the Managed Care Biologics and Injectables Index: Q1 2020, between Feb. 25, 2020, and April 1, 2020, Zitter surveyed 51 commercial payers with 138.1 million covered lives about their anticipated management of Orladeyo. Payers covering 93% of lives said they likely would manage it to label and not allow off-label use.

Among 46 commercial payers with 130.3 million covered lives surveyed during the same time period, payers with 74% of covered lives said they were likely to manage Orladeyo at parity to the prophylactic therapies. And even though it is the only oral HAE drug, payers with 80% of lives said they were unlikely to manage it separately from the other drugs based on route of administration.

Among providers who would transition current patients to Orladeyo, the most likely prophylactic agent to transfer from was Cinryze, cited by 42%; followed by Haegarda, at 25%; and Takhzyro at 8%.

BioCryst has priced Orladeyo at $485,000 per person per year, which is slightly more than the $450,000 PPPY that Evercore ISI expected, according to analyst Liisa Bayko in a Dec. 4 research note. That price, though, is lower than Haegarda’s $510,000 PPPY and Takhzyro’s $566,000, she pointed out.

“As an oral, once-daily option, Orladeyo provides significant attack reduction without the burden associated with injectables — the hallmark of treatment options,” wrote Bayko. “Our market research showed that patients and physicians were eagerly awaiting an oral option, with anticipated use of Orladeyo reaching 34% of prophylaxis HAE market by [year-end] 2021 — driven by switching and growth of the market with use of prophylaxis rising from 60% to 80% over time.”

Supreme Court’s ACA Ruling May Upend Biosimilars Market

January 6, 2021

As the Supreme Court decides on the fate of the Affordable Care Act (ACA), much of the focus has been on the people who would lose health insurance coverage and protections for pre-existing conditions if the law is overturned. Another ramification of such a ruling is that the biosimilars market could be completely upended.

The Biologics Price Competition and Innovation Act of 2009 (BPCIA) created the 351(k) biosimilar pathway. After more than one attempt to get a stand-alone bill to pass, lawmakers made it part of the ACA, and it became law on March 23, 2010.

By Angela Maas

As the Supreme Court decides on the fate of the Affordable Care Act (ACA), much of the focus has been on the people who would lose health insurance coverage and protections for pre-existing conditions if the law is overturned. Another ramification of such a ruling is that the biosimilars market could be completely upended.

The Biologics Price Competition and Innovation Act of 2009 (BPCIA) created the 351(k) biosimilar pathway. After more than one attempt to get a stand-alone bill to pass, lawmakers made it part of the ACA, and it became law on March 23, 2010.

Industry observers expect a decision on the case California v. Texas by June 2021, according to various sources. And opinions among industry experts vary on what the court will decide.

“I do think it is severable, but I am optimistic that that won’t be needed,” says one industry expert who declines to be identified.

A second industry expert who declines to be identified points out that “there have been a fair amount of amicus briefings,” which will make the court “think twice” about doing away with the BPCIA.

“I think the outcome of the Affordable Care Act case before the Supreme Court will be similarly mixed as a ruling like last time,” says F. Randy Vogenberg, Ph.D., principal at the Institute for Integrated Healthcare. “I doubt they will rule the ACA is severable but will keep that door open….If the court strikes down the ACA entirely, biosimilars on the U.S. market or in the FDA approval pipeline would have to either be grandfathered in or face a regulatory wind-down.”

If the ACA and thus the BPCIA are struck down, “personally, I think it’s unlikely that medicines would be pulled off the market,” says source No. 2. However, if the ACA is invalidated, the Supreme Court likely would include “guidance to regulators for carrying out their order.”

“I would not expect FDA to de-approve anything already approved, but the pipeline might get more muddled,” says the first source.

All that said, “[g]ood business practices would recommend that biosimilar manufacturers should be preparing for the possibility of the ACA, and thus the BPCIA, being struck down,” recommends Vogenberg. “What should they be doing is scenario planning and being prepared for the best or worst and everything in between. If biosimilars are not available, this could impact payers that have them on formulary should a disruption occur in their marketing.”

FDA’s Approval of Sogroya May Change GH Class Management

November 4, 2020

When the FDA approved Novo Nordisk, Inc.’s Sogroya (somapacitan-beco) for the replacement of growth hormone in adults with growth hormone deficiency on Aug. 28, it became the only long-acting agent on the market.

There are seven short-acting growth hormones currently available to treat adults with growth hormone deficiency, all of them branded forms of somatropin. Differences among the products, all of which are self-administered, include the strengths available and the type of device to deliver the treatment. But all of them must be administered daily. Sogroya, which also is self-administered, is the only FDA-approved product with weekly dosing.

By Angela Maas

When the FDA approved Novo Nordisk, Inc.’s Sogroya (somapacitan-beco) for the replacement of growth hormone in adults with growth hormone deficiency on Aug. 28, it became the only long-acting agent on the market.

There are seven short-acting growth hormones currently available to treat adults with growth hormone deficiency, all of them branded forms of somatropin. Differences among the products, all of which are self-administered, include the strengths available and the type of device to deliver the treatment. But all of them must be administered daily. Sogroya, which also is self-administered, is the only FDA-approved product with weekly dosing.

Mesfin Tegenu, R.Ph., president of PerformRx, LLC, points out that Sogroya “is a human growth hormone (hGH) analog — an hGH with an added albumin-binding moiety. Up until this point, all hGH products have been a recombinant product, identical copies of hGH (rhGH). The half-life of somapacitan is measured in days (two to three days) while the half-life of rhGH (somatropin) is measured in hours (approximately two-and-a-half hours). The extended half-life of somapacitan allows less frequent (weekly) dosing.”

He says that payers typically have prior authorization on somatropin, with “controls including diagnostic and lab values as prerequisites.” A prescription from an endocrinologist is also a “common practice.”
“Somapacitan is likely to be managed similar to all the other rhGH class of drugs,” Tegenu says, adding that “it is reasonable to classify it as a second-line or nonpreferred agent whose use is allowed only after a trial and failure of or other medical reason for not using a preferred daily rhGH.”

For the Managed Care Biologics and Injectables Index: Q1 2020, Zitter Insights surveyed between Feb. 25 and April 1 51 commercial payers with 138.1 million covered lives, and respondents with 55% of the lives said they expect to cover at least one long-acting therapy at parity with a preferred short-acting one. Payers with 11% of the covered lives said they expected to prefer a long-acting agent over all other products.

Zitter also polled 25 endocrinologists about their anticipated reaction to the availability of a long-acting growth hormone. Three-fourths of them said they were somewhat likely and highly likely to prescribe it to patients new to therapy, and 68% said they were somewhat likely and highly likely to shift current patients to it.

FDA Approved Two PARP Inhibitors for Prostate Cancer

August 11, 2020

Although poly ADP-ribose polymerase (PARP) inhibitors are not new to the market, two of them recently gained approval for use in prostate cancer for the first time. The therapies will bring a new option for the treatment of certain subpopulations of patients.

On May 19, the FDA expanded the label of AstraZeneca and Merck & Co., Inc.’s Lynparza (olaparib) to include the treatment of people with deleterious or suspected deleterious germline or somatic homologous recombination repair gene-mutated metastatic castration-resistant prostate cancer who have progressed following treatment with Xtandi (enzalutamide) or Zytiga/Yonsa (abiraterone acetate).

By Angela Maas

Although poly ADP-ribose polymerase (PARP) inhibitors are not new to the market, two of them recently gained approval for use in prostate cancer for the first time. The therapies will bring a new option for the treatment of certain subpopulations of patients.

On May 19, the FDA expanded the label of AstraZeneca and Merck & Co., Inc.’s Lynparza (olaparib) to include the treatment of people with deleterious or suspected deleterious germline or somatic homologous recombination repair gene-mutated metastatic castration-resistant prostate cancer who have progressed following treatment with Xtandi (enzalutamide) or Zytiga/Yonsa (abiraterone acetate).

On May 15, the FDA gave accelerated approval to Clovis Oncology, Inc.’s Rubraca (rucaparib) for the treatment of adults with a deleterious BRCA mutation (germline and/or somatic)-associated metastatic castration-resistant prostate cancer who have been treated with androgen receptor-directed therapy and a taxane-based chemotherapy.

Two other PARP inhibitors — GSK’s Tesaro, Inc.’s Zejula (niraparib) and Pfizer Inc.’s Talzenna (talazoparib) — are on the market, and both are in clinical trials for prostate cancer.

Lynparza’s and Rubraca’s approvals are “indicative of the growing knowledge we are gaining with respect to the intermediary pathways within the cells regulating DNA repair as it relates to tumor growth,” says Winston Wong, Pharm.D., president of W-Squared Group.

The PARP inhibitors will impact “refractory patients who have failed standard-of-care therapies,” notes Mesfin Tegenu, R.Ph., president of PerformRx, LLC. First-line treatment will be with antiandrogens or taxanes, he explains: Zytiga, Yonsa, Jevtana (cabazitaxel), Taxotere (docetaxel) or Xtandi. Then the top competitors in the second-line setting will be Lynparza, Rubraca and Keytruda (pembrolizumab), he says.

Asked how the two PARP inhibitors compare with other therapies in the class, Tegenu points out that “Lynparza had higher objective response rates and better radiographic progression-free survival compared to enzalutamide and abiraterone. It also showed benefit compared to docetaxel. Men with specific mutations may benefit more with PARP inhibitors.”

“Rubraca after receiving taxane therapy showed benefit,” he continues. “It is currently being compared to abiraterone, enzalutamide or docetaxel in an ongoing clinical trial. It has accelerated approval contingent upon verification of success in this trial.”

Uncertainties Over Effectiveness and High Costs Surround DMD Therapies

June 10, 2020

Since 2016, the FDA has approved a handful of therapies to treat Duchenne muscular dystrophy (DMD). But some uncertainty exists over their effectiveness, in addition to concerns about their costs.

When DMD is suspected, a blood test that measures creatine kinase (CK) levels is performed. “CK is an enzyme found in abnormally high levels when muscle is damaged,” says Mesfin Tegenu, R.Ph., president of PerformRx, LLC. “The detection of an elevated CK level leads to molecular genetic testing to confirm a definitive diagnosis of DMD.”

By Angela Maas

Since 2016, the FDA has approved a handful of therapies to treat Duchenne muscular dystrophy (DMD). But some uncertainty exists over their effectiveness, in addition to concerns about their costs.

When DMD is suspected, a blood test that measures creatine kinase (CK) levels is performed. “CK is an enzyme found in abnormally high levels when muscle is damaged,” says Mesfin Tegenu, R.Ph., president of PerformRx, LLC. “The detection of an elevated CK level leads to molecular genetic testing to confirm a definitive diagnosis of DMD.”

In February 2017, the FDA approved then-manufacturer Marathon Pharmaceuticals LLC’s Emflaza (deflazacort). The company said it would be priced at $89,000, which sparked outrage since people have been buying a generic version from overseas since the 1990s for about $1,000 per year. After the backlash, Marathon ultimately sold the drug to PTC Therapeutics Inc., which launched it later that year with a $35,000 annual price tag. Since then, PTC has raised the price to more than Marathon’s original one.

In September 2016, the FDA gave accelerated approval to Sarepta Therapeutics, Inc.’s Exondys 51 (eteplirsen). The dystrophin gene has 79 exons, and about 80% of people with DMD have genotypes that are amenable to exon skipping. Exondys 51 targets those with a mutation of the DMD gene that is amenable to exon 51 skipping.

Sarepta also has a second exon-skipping therapy, Vyondys 53 (golodirsen), which treats DMD in people with a mutation amenable to exon 53 skipping. The FDA gave the drug accelerated approval in December, almost four months after the agency rejected the drug through a complete response letter.

Both drugs are weight-based with similar prices: about $300,000 per year but up to $1 million annually.

“It’s unclear how much a health plan may spend on someone with DMD; however, a recent study from the Muscular Dystrophy Association found that the annual cost for DMD for U.S. society as a whole is around $362-$488 million dollars,” says Tegenu. “The price of the newer DMD therapies (Exondys 51 and Vyondys 53) are both estimated to cost approximately $750,000 per year for the treatment of one patient.”

Pharma manufacturers continue to focus on the DMD space, and several products, including gene therapies, are in the pipeline.