Author: Randy Chase

The FDA recently approved a new ORAL therapy, Rezurock (belumosudil) from Kadmon Pharmaceuticals, with an indication for adult and pediatric patients with chronic graft-versus-host disease (chronic GVHD).

There are about 14,000 patients with GVHD in the U.S. each year, and between 7,000 and 10,000 of them need systemic therapy. Roughly 60% of those patients have already tried and failed on two or more prior therapies.

Kadmon plans to launch Rezurock in late August at a monthly ‘bargain’ price of $15,500 per 30-count bottle….. that’s $186,000 annually.

Given the relatively small US patient population and cost, Kadmon has decided to launch this new therapy into limited distribution. Onco360 has announced that it will be a limited distribution partner.

Click here for patient information

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FDA approves Belumosudil for chronic graft-versus-host disease

On July 16, 2021, the Food and Drug Administration approved belumosudil (Rezurock, Kadmon Pharmaceuticals, LLC), a kinase inhibitor, for adult and pediatric patients 12 years and older with chronic graft-versus-host disease (chronic GVHD) after failure of at least two prior lines of systemic therapy.

Efficacy was evaluated in KD025-213 (NCT03640481), a randomized, open-label, multicenter dose-ranging trial that included 65 patients with chronic GVHD who were treated with belumosudil 200 mg taken orally once daily.

The main efficacy outcome measure was overall response rate (ORR) through Cycle 7 Day 1 where overall response included complete response (CR) or partial response (PR) according to the 2014 criteria of the NIH Consensus Development Project on Clinical Trials in Chronic Graft-versus-Host Disease. The ORR was 75% (95% CI: 63, 85); 6% of patients achieved a CR, and 69% achieved a PR. The median time to first response was 1.8 months (95% CI: 1.0, 1.9). The median duration of response, calculated from first response to progression, death, or new systemic therapies for chronic GVHD, was 1.9 months (95% CI: 1.2, 2.9). In patients who achieved response, no death or new systemic therapy initiation occurred in 62% (95% CI: 46, 74) of patients for at least 12 months since response.

The most common adverse reactions (≥ 20%), including laboratory abnormalities, were infections, asthenia, nausea, diarrhea, dyspnea, cough, edema, hemorrhage, abdominal pain, musculoskeletal pain, headache, phosphate decreased, gamma glutamyl transferase increased, lymphocytes decreased, and hypertension.

The recommended dosage of belumosudil is 200 mg taken orally once daily with food.

This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with Australia’s Therapeutic Goods Administration, Health Canada, Switzerland’s Swissmedic, and the United Kingdom’s Medicines and Healthcare products Regulatory Agency.

This review used the Real-Time Oncology Review (RTOR) pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application 6 weeks ahead of the FDA goal date.

This application was granted priority review and breakthrough therapy designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

We’ve often written about the legal pitfalls that specialty pharmacies may encounter that end up costing them financially (HIPAA violations are top of mind). Today we take a more positive tack. The article below is an insightful review of a number of tactics that can navigate around some of those pitfalls.

Written by an attorney with the rights of specialty pharmacies in mind, we are alerted to options available to address several of the most irksome issues faced by specialty pharmacies today (some have been around for years).

Here is a short list to whet your appetite to read the full article:
How does my specialty pharmacy navigate through Network Access / Payer & PBM Obstacles / and Any Willing Provider Laws?
What are the emerging challenges related to White and Brown Bagging?
Can I do employ Fair Pharmacy Audit Laws/ and what are the legal implications related to Clawbacks?
What Prompt Payment Laws can safeguard my reimbursements?

These won’t cure all that ails specialty pharmacies in today’s complicated market, but it may help put out some of the fires.

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Legal Tools to Protect Specialty Pharmacies

JULY 16, 2021 — In today’s complicated pharmacy benefits landscape, with increasing dominance by a collection of vertically integrated payor and pharmacy benefit manager (PBM) networks, hospital and health-system specialty pharmacies have some legal tools that they can use to address challenges, such as network access, mandatory white-bagging policies and payor activities in the 340B space.

That was the message from Jesse Mr. Dresser, Esq, an attorney with the health care law firm Frier Levitt LLC, in a session on legal conundrums in specialty pharmacy held during the 2021 ASHP Specialty Pharmacy Conference, held virtually.

Mr. Dresser advised specialty pharmacies that no matter the issue—compliance, network admission, site-of-care policies or reimbursement—it’s important to start with the patient and their type of plan. “That will dictate what laws and rules apply and what your rights and obligations are,” he said.

Types of specialty pharmacy networks

1. Closed or exclusive. “These are the ones where the sponsors are not allowing anyone in except their own wholly owned specialty pharmacy,” Mr. Dresser said. “We typically see these arrangements in the employer-sponsored commercial market. Large plan sponsors with thousands or hundreds of thousands of employees, like Pepsi-Cola, typically self-insure rather than spend an extra 10% to 15% on premiums on behalf of their employees, but they will still contract with an insurance company to administer their claims and PBMs to administer their pharmacy benefits. In this context, state laws don’t really apply and federal rules like those involving Medicare or Medicaid [also] don’t really apply.” Plans like these, he noted, are subject only to the Employee Retirement Income Security Act (ERISA), which is silent on what pharmacies must be in a network.
2. “Open,” but with heightened admission criteria. Such criteria include requirements for multiple forms of accreditation or licensure in all 50 states.
3. Truly open specialty pharmacy networks. “These are typically found in Medicare networks, where there is a robust federal Any Willing Provider law and a prohibition on payors from limiting who can be in the network,” Mr. Dresser said.

White and Brown Bagging
The growing trend among PBMs to move claims processing from the medication side to the pharmacy side, requiring more white and brown bagging—a hot topic throughout the meeting—has had a major impact on hospital infusion, Mr. Dresser said. “About this time last year, several large payors took virtually identical steps to begin to require that in-office infused medications be filled at their wholly owned specialty pharmacies, and placing limitations, or removing the ability altogether, on providers’ ability to source and seek reimbursement for medications administered in their facilities.”

There are laws being proposed in some states that would make mandatory white bagging illegal, but what can hospital and health-system specialty pharmacies do in the meantime?

“Depending on the type of plan involved, you might be able to deploy Any Willing Provider,” he said. “All 50 states and the District of Columbia, through Medicare Part D, are subject to the federal Any Willing Provider law, meaning that any willing pharmacy able to participate in a network’s terms and conditions has to be allowed in. The law is fairly robust, and its guidance requires that those terms and conditions have to be reasonable and relevant. It has been used successfully to protect not only network access, but fair and appropriate reimbursement for specialty pharmacies to participate in Medicare Part D programs.”

There also are some state-based Any Willing Provider laws as well as state laws banning mandatory mail-order pharmacy. “About 33 states have some level of this kind of protection,” Mr. Dresser said. “I would encourage anyone facing any kind of exclusion to figure out what type of network the patients you are not being able to fill for are in, and then see if you can use some of these legal tools to your advantage.”

Other legal tools available to specialty pharmacies include:
Fair pharmacy audit laws.
“These laws apply at the state level, typically in the context of commercial insurance and not necessarily ERISA or Medicare,” Mr. Dresser said. “They provide time limits on PBM audits, as well as audit appeal procedures. They often limit the number of prescriptions that can be looked at in a given audit, and helpfully, prohibit recoupment for clerical errors or things that can be ‘cured.’”

Prompt payment laws
“These include look-back periods limiting PBM audits,” Mr. Dresser explained. “Florida, for example, says you can’t go back more than 30 months in terms of a repayment demand. They also prohibit PBMs from unilaterally offsetting claims to recoup on audits, saying, ‘You owe us $100,000, and we’re going to recoup it immediately. You can appeal but we’re going to start now.’ If you’re facing an audit and potential recoupment, this is a good tool to have in your arsenal.

Mr. Dresser also spotlighted recent actions by PBMs in the 340B space. “They are trying to retain the spread between the costs of the 340B drug and the PBM reimbursement,” he said. “They send out notices to pharmacies requiring them to submit 340B claims with a submission clarification code to signal to the PBM that it is a 340B claim.”

This typically involves the use of a Submission Clarification Code of “20” in the NCPDP Field 420-DK. If a claim is 340B, the PBM then reimburses the pharmacy at a lower rate, for example, average wholesale price (AWP) – 30%, compared with a rate of AWP – 15% for non-340B claims.

“Essentially, PBMs are looking to usurp that savings for themselves,” Mr. Dresser said. “This is not necessarily limited to Medicaid programs managed by PBM; it could include commercial plans and often does. They are also using third-party administrators to get access to this information. Some PBMs own their own third-party administrators, so they might have the ability to make the determination, even if the pharmacy didn’t submit the clarification code at the point of sale.”

Mr. Dresser noted that there has been some success in pushing back against these efforts. “The tides have turned a bit in state legislation,” he said. “Some states, including most recently Ohio, have passed laws prohibiting PBMs from differentiating 340B and non-340B pricing. So, if you are facing mandates from a PBM that you use the clarification code, or otherwise encountering 340B-specific pricing, I encourage you to speak to counsel who can guide you on some of the recent tools that are available.”

Click Here to access the article in Specialty Pharmacy Continuum

Earlier this month the FDA approved a ‘new’ combination therapy, Darzalex Faspro (daratumumab and hyaluronidase-fihj), from Janssen Biotech. Darzalex was originally approved in 2015 with an indication for multiple myeloma. The combo therapy is ‘new and improved’ for the same indication.

Darzalex Faspro is a subcutaneous combination injection (over 5 minutes) and is used together with bortezomib, melphalan, and prednisone to treat newly diagnosed multiple myeloma (a type of bone marrow cancer) in patients who cannot receive autologous stem cell transplant (transplant that uses their own stem cells).

Dosing Schedule:
Once weekly Weeks 1-8, Once every 2 weeks from Weeks 9 to 24, Once every 4 weeks starting with Week 25 — until disease progression or unacceptable toxicity (see prescribing information for full details).

The standard dose schedule requires 23 doses over the first 52 weeks on therapy. Published price for the 15ml dose is $8296. The annual cost tips in at $190,800.

The ‘improved’ formulation is a lot more expensive than the early version Darzalex as well as its leading competitors, Pomalyst at$147,000 and Kyprolis at $114,000 per year.

Janssen did not announce details for distribution. Patients may be burdened with frequent office visits in the early stage of therapy, but that shifts to once monthly after the first nine weeks. As such, it is likely that patients will receive therapy in the office vs. home injection. That will diminish the need for a specialty pharmacy distribution model, but Janssen is very prone to SP limited distribution. Time will tell.

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FDA approves daratumumab and hyaluronidase-fihj with pomalidomide and dexamethasone for multiple myeloma

On July 9, 2021, the Food and Drug Administration approved daratumumab and hyaluronidase-fihj (Darzalex Faspro, Janssen Biotech, Inc.) in combination with pomalidomide and dexamethasone for adult patients with multiple myeloma who have received at least one prior line of therapy including lenalidomide and a proteasome inhibitor.

Efficacy was evaluated in APOLLO (NCT03180736), an open-label, active-controlled trial with 304 patients randomized (1:1) to Darzalex Faspro with pomalidomide and dexamethasone (Pd) vs Pd alone.

The main efficacy outcome measure was progression-free survival (PFS). The median PFS was 12.4 months in the Darzalex Faspro-Pd treatment group and 6.9 months in the Pd treatment group (HR 0.63; 95% CI: 0.47, 0.85; p=0.0018), representing a 37% reduction in the risk of disease progression or death for patients treated with Darzalex Faspro-Pd versus Pd.

The most common adverse reactions (≥20%) in patients with multiple myeloma who received Darzalex Faspro-Pd are fatigue, pneumonia, upper respiratory tract infection, and diarrhea.

The recommended dosage of Darzalex Faspro is 1,800 mg/30,000 units (1,800 mg daratumumab and 30,000 units hyaluronidase) administered subcutaneously into the abdomen over approximately 3 to 5 minutes according to the recommended schedule.

View full prescribing information for Darzalex Faspro.

The FDA approved this application 2 months ahead of the FDA goal date.

It’s about time.
It has been quite a while since we’ve heard about a specialty pharmacy acquisition. Over recent years there was a race to the top to acquire the remaining ‘gems’ that were primed for acquisition. Suddenly that well ran dry.

The news detailed below isn’t quite on par with those earlier big acquisitions. Two ‘relatively’ small companies will result in BioMatrix growing again. They have had several other small add-ons to bolster size and scale. The most recent acquisition of InfuCare will open new therapeutic avenues for BioMatrix, especially with infusion services. Those with any hands-on experience in the infusion market know that running an infusion shop is much more complicated than traditional (pick-pack-ship-service) specialty pharmacy.

So, turn back the clock quite a few years to when specialty pharmacies grew both organically and by scooping up relatively small organizations especially if they were acretive. It would not be surprising, therefore, to see BioMatrix emerge as a much larger organization should it continue to follow that strategy and become a gem in its own right.

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BioMatrix Specialty Pharmacy Acquires InfuCare Home Infusion Pharmacy

PLANTATION, Fla., July 6, 2021 /PRNewswire/ — BioMatrix Specialty Pharmacy announced today the acquisition of InfuCare LTD, in Tyler, Texas. This infusion focused specialty pharmacy adds a brick-and-mortar location in a key geographic area, expands the organization’s national footprint, and provides access to additional covered lives in one of the nation’s largest states. The acquisition is the latest of several transactions that have positioned BioMatrix as one of the largest privately held specialty pharmacies in the United States.

The staff at InfuCare have extensive experience in key therapeutic categories for BioMatrix. The organization is well versed in chronic, complex conditions requiring home infusion including IVIG, anti-infectives, parenteral nutrition and more. The organization has been recognized for providing exemplary home infusion and specialty pharmacy services in Texas. InfuCare is accredited by the National Association of Boards of Pharmacy.

BioMatrix CEO Nick Karalis commented, “We are pleased to welcome the InfuCare team as part of the BioMatrix family. A Texas pharmacy location is part of our strategic plan to expand our infusion services and increase access to covered lives. With complimentary core competencies and shared values of exceptional patient care, together we will improve health and shape a more promising future for the patients we serve,” Karalis said.

“The leadership and staff at InfuCare are delighted to begin our partnership with BioMatrix,” stated Gary Wyatt, Partner of InfuCare, LTD. “Our goal over the last 21 years has been to provide an exceptional and personal level of infusion care to our patients in the east Texas region. Having interacted with BioMatrix leadership over the last several months, we are confident that our focus and theirs will be complementary and will lead to an even greater level of care for both infusion and specialty patients in our region and beyond. We are excited to join such a highly respected company and look forward to a long and impactful relationship with BioMatrix.”

Additional information on BioMatrix and InfuCare can be found at www.biomatrixsprx.com and https://infucare.net

About BioMatrix Specialty Pharmacy
BioMatrix Specialty Pharmacy, an Inc. 5000 company, offers comprehensive, nationwide specialty pharmacy services and digital health technology solutions for patients with chronic, difficult to treat conditions. Our commitment to every patient is to provide individualized pharmacy services, timely access to care, and focused education and support. We offer a tailored approach for a wide range of therapeutic categories, improving health and empowering patients to experience a higher quality of life.

The public relations battle surrounding White Bagging is heating up.
Who’s on each side?
Depends on who you ask….!
On one side, hospitals are claiming that their very existence is being threatened due to White Bagging policies.
On the other side are the PBMs and the payers.
But, is there yet a third side? We will get to that.

First, what is White Bagging?
As defined by the hospitals in the article link below…..
White Bagging consists of “policies that require hospitals administering certain high-cost medications in an outpatient setting [actually inpatient as well] to receive those medications from third parties contracted with the health plan, instead of providing those medications directly from the hospital pharmacy inventories.” Increasingly, those third parties are specialty pharmacies acting as specialty distributors, under a distributor’s license (no prescription required) or as the pharmacy (with a prescription).

What’s at stake? Money and control.
The number of rare therapies approved over the past two years has mushroomed. Most of the therapies have been $HUGE$ dollar meds that are hospital administered, often at leading national medical centers. These providers are very concerned about money and control. If they can buy directly and bill under often outdated, traditional contract terms (which never envisioned meds costing in the hundreds of thousands of dollars for a one-time infusion and may still pay them at U&C rates) then chances are they will realize a larger Net profit. If a specialty pharmacy is inserted into that scenario, they may not be able to realize any profit if the SP directly bills the PBM as a pharmacy claim or payer via a medical claim.

It is no surprise that the hospitals are now upping the ante and turning to the courts and even state legislatures, where they may have significant influence, to seek relief and regain control.

But…. who is the third party to this battle? Manufacturers.
The pharmaceutical manufacturers proliferated the “White Bagging” war by selecting one or a handful of specialty pharmacies to be their preferred distributor(s) for these new infused therapies. Traditional distributors can’t perform all the functions of a specialty pharmacy as they are prohibited from making direct patient contact. Manufactures realized that SPs can help them out with managing patient care, ensuring compliance, tracking outcomes for FDA reporting, in addition to all the traditional SP patient stuff such as clearing prior authorizations and financial assistance. When payers and PBMs realized what was happening they got creative and saw a way to insert utilization review and tighter benefits management into the mix, things that SPs are also adept at juggling.

It is also noteworthy to mention that SPs are also inventorying their meds for distribution. Traditional distributors charge manufacturers a percentage for their limited services…. better to pay an SP for the full-service package vs. just “park, pack, and ship.”

So, it is surprising that the hospital lobby is focusing its ire only on the payers and PBMs, allowing the manufacturers off the hook. Then again, there are a lot of big research dollars that flow from manufacturers to the same big medical centers in new drug trials….. just sayin’.

So, read the article below for a good update on what the leading payers are doing related to “White Bagging”.

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Payers Attempt to Impose “White-Bagging” Policies on Hospitals

CLICK HERE TO READ THE FULL ARTICLE

Here’s something that you don’t see every day…..

We published the report below in November 2019 detailing the approval of Exservan, a drug first approved twenty-five-years ago. Well, it is back in the news. Specifically, Mitsubishi Tanabe Pharma America, just announced that it is now changing its marketing strategy and is pushing this product into limited distribution. It has selected PANTHERx Rare as their exclusive specialty pharmacy provider of this oral film product.

That FDA approval was originally given to Aquestive Therapeutics. The shift to Mitsubishi may be the catalyst behind the change in access strategy.

There was uncertainty about the cost of Exservan when it was approved. It is now priced on par with its primary competitor, Tiglutik (oral suspension). The current cost for Exservan oral film 50 mg is around $3,291 for a supply of 60 films.

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FDA Approves New Form of a 25-Year-Old Drug – Exservan

11/2019

The FDA just approved a new (actually not so new) therapy for a very under served disease, amyotrophic lateral sclerosis (ALS). The approval was for an oral film version of a therapy, Riluzole, that was approved in 1995….. yes, 24 years ago!

Riluzole is a generic of the brand drug Rilutek, which is still on the market. The brand runs about $35,000 a year while the generic is now only $10,000 annually. Both, however are in tablet form, which presents a real challenge for patients that can’t easily swallow.

Before you ask why we are covering the approval of a copy of a very old drug let me explain.
In 2017 the FDA approved a next generation therapy for ALS, Radicava, which now costs about $145k annually. However, Radicava is IV therapy requiring multiple infusions per month….. and that presents access challenges for the majority of ALS patients who are not ambulatory. As such, Radicava hasn’t had much uptake.

Then, in 2018, the FDA approved Tiglutik, a form of Riluzole (yes, the same old generic). Tiglutik is an oral suspension….. easier for ALS patients to take…. but requires the patient or care giver to use a syringe to slowly drip-drip the medication into the mouth. The cost of Tiglutik, however, is $25k annually (2.5X the cost of the generic oral tablet form). (NOTE: The cost of Tiglutik has risen more than $10,000 since 2019.)

Finally we reach the end of this now convoluted story….. Exservan.
Because it is an oral film, Exservan can be easily administered to an ALS patient allowing the medication slowly dissolve under the tongue. While pricing hasn’t been announced it is likely to be in line with Tiglutik.

We missed one….!
The drug being recapped today was approved back in late February. We put it on the shelf till we could determine whether this would be distributed by a specialty pharmacy and, lo and behold, it will.

The FDA approval is for a new INFUSED therapy, Nulibry (fosdenopterin) from Origin Biosciences (one of several BridgeBio affiliates), to reduce the risk of death due to Molybdenum Cofactor Deficiency Type A, a rare, genetic, metabolic disorder. The condition typically presents in the first few days of life as evidenced by intractable seizures, brain injury and death.

Once approved following genetic testing, Nulibry will require daily infusions .
Only around 150 patients worldwide are believed to have the disease,

The drug will carry a list price of $500,000 per year. Yet, it’s only expected to bring in some $10 million at its peak….. I’ll do the math for you….. that’s only 20 patients.

It was also announced that Biologics by McKesson was selected by Origin Biosciences as the exclusive specialty pharmacy provider for Nulibry.

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FDA Approves First Treatment for Molybdenum Cofactor Deficiency Type A

February 26, 2021 — Today, the U.S. Food and Drug Administration approved Nulibry (fosdenopterin) for injection.

“Today’s action marks the first FDA approval for a therapy to treat this devastating disease,” said Hylton V. Joffe, M.D., M.M.Sc, director of the Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine in the FDA’s Center for Drug Evaluation and Research. “The FDA remains committed to facilitating the development and approval of safe and effective therapies for patients affected by rare diseases—an area of critical need.”

Patients with Molybdenum Cofactor Deficiency Type A experience severe and rapidly progressive neurologic damage including intractable seizures, feeding difficulties and muscle weakness from the accumulation of toxic sulfite metabolites in the central nervous system. Most patients die in early childhood from infections. Before today’s approval, the only treatment options included supportive care and therapies directed towards the complications arising from the disease.

Patients with Molybdenum Cofactor Deficiency Type A cannot produce a substance known as cyclic pyranopterin monophosphate (cPMP). Nulibry is an intravenous medication that replaces the missing cPMP. The effectiveness of Nulibry for the treatment of Molybdenum Cofactor Deficiency Type A was demonstrated in 13 treated patients compared to 18 matched, untreated patients. The patients treated with Nulibry had a survival rate of 84% at three years, compared to 55% for the untreated patients.

The most common side effects included complications related to the intravenous line, fever, respiratory infections, vomiting, gastroenteritis and diarrhea.

Phototoxicity (injury to the skin and eyes from certain types of light, such as sunlight) was seen in animals, so patients treated with Nulibry should avoid exposure to sunlight and wear sunscreen, protective clothing, and sunglasses when exposed to the sun.

The FDA granted this application Priority Review and Breakthrough Therapy designations. Nulibry also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases. The sponsor is also receiving a Rare Pediatric Disease Priority Review Voucher under a program intended to encourage development of new drugs and biologics for the prevention and treatment of rare pediatric diseases. A voucher can be redeemed by a sponsor at a later date to receive Priority Review of a subsequent marketing application for a different product.

The FDA granted the approval of Nulibry to Origin Biosciences, Inc.

The FDA recently approved a specialty ORAL therapy, Truseltiq (infigratinib) from QED Therapeutics (one of several BridgeBio affiliates). Truseltiq was granted an indication for unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test.

Cholangiocarcinoma (CCA), a cancer of the bile ducts in the liver, affects some 20,000 people in the U.S. and European Union a year, and FGFR2 genetic aberrations are present in around 15% to 20% of those patients. Currently, the median five-year survival rate is just 9%.

BridgeBio will launch Truseltiq at a price of $21,500 per month, according to analysts. It will cost around $64,500 every three months with an average treatment duration of around six months and eight or nine cycles. It is priced nearly on par with a competing therapy with the same indication, Premazyre.

Given the small patient population, the need to obtain a genetic test, its on/off dosing schedule, and high cost, it is highly likely that Truseltiq will launch in limited distribution.

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FDA grants accelerated approval to Truseltiq for metastatic cholangiocarcinoma

On May 28, 2021, the Food and Drug Administration granted accelerated approval to infigratinib (Truseltiq, QED Therapeutics, Inc.), a kinase inhibitor for adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test.

The FDA also approved FoundationOne® CDx (Foundation Medicine, Inc.) for selection of patients with FGFR2 fusion or other rearrangement as a companion diagnostic device for treatment with infigratinib.

Efficacy was demonstrated in CBGJ398X2204 (NCT02150967), a multicenter open-label single-arm trial, that enrolled 108 patients with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with an FGFR2 fusion or rearrangement as determined by local or central testing. Patients received infigratinib 125 mg orally once daily for 21 consecutive days followed by 7 days off therapy, in 28-day cycles until disease progression or unacceptable toxicity.

The major efficacy outcome measures were overall response rate (ORR) and duration of response (DoR), as determined by blinded independent central review according to RECIST 1.1. The ORR was 23% (95% CI: 16, 32), with 1 complete response and 24 partial responses. Median DoR was 5 months (95% CI: 3.7, 9.3). Among the 23 responders, 8 patients maintained the response for 6 months or more.

The most common (incidence ≥ 20%) adverse reactions were hyperphosphatemia, increased creatinine, nail toxicity, stomatitis, dry eye, fatigue, alopecia, palmar-plantar erythrodysesthesia syndrome, arthralgia, dysgeusia, constipation, abdominal pain, dry mouth, eyelash changes, diarrhea, dry skin, decreased appetite, vision blurred and vomiting. The serious risks include hyperphosphatemia and retinal pigment epithelial detachment and monitoring for these adverse reactions during treatment is recommended.

This indication is approved under accelerated approval based on the overall
response rate and duration of response. Continued approval for this indication
may be contingent upon verification and description of clinical benefit in
confirmatory trial(s).

This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with the Australian Therapeutic Goods Administration (TGA) and Health Canada. The application reviews are ongoing at the other regulatory agencies.

This review used the Real-Time Oncology Review (RTOR) pilot program, which streamlined data submission prior to the filing of the entire clinical application, as well as the Assessment Aid and the Product Quality Assessment Aid (PQAA), voluntary submissions from the applicant to facilitate the FDA’s assessment.

This application was granted priority review, fast-track designation, and orphan drug designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

Get yer Lumakras!
Lumakras here!

90+% of FDA specialty approvals launched through limited distribution in 2011….. and that trend continues in 2021. As frequent readers know, we very often have to say that the limited distribution partners, be they specialty pharmacies and/or specialty distributors, have not been disclosed by the manufacturer. That was the case in last week’s report on the FDA approval of Lumakras for Alzheimer’s where we were only able to confirm one SP in the program as of the time we sent the report.

Given the significant buzz about this new product we were delighted to receive, and now share, a chart listing all LD Specialty Pharmacies and Specialty Distributors that will be handling this new product. (See Below) We hope that more manufacturers similarly follow Amgen’s lead in publishing such a list.

In a flood of approvals in the last days of May the FDA green lighted a new ORAL therapy, Lumakras (sotorasib) from Amgen, three months ahead of schedule. Lumakras is the first treatment for adult patients with non-small cell lung cancer (NSCLC) with a genetic KRAS G12C mutation and have received at least one prior systemic therapy.

KRAS mutations account for approximately 25% of mutations in NSCLC with the G12C variant representing about 13%. Of the 2.2 million new lung cancer cases diagnosed each year globally, about 84% are of the NSCLC type.

Oncologists are very upbeat about this approval as there were no good therapy options for NSCLC patients with the mutation. Amgen is first to get a new therapy to the FDA finish line, but other companies are on well into late stage trials.

Analysts expressed some surprise at the of $17,900 price per month announced by Amgen. None the less, Lumakras is forecast to be a $1 billion drug somewhat quickly. That may be tempered by the FDA’s request to Amgen that they evaluate a significantly lower dose for the drug. If that happens, the forecast likely be revised.

We have confirmed that Lumakras will launch into Limited Distribution. Onco360 has been named as the specialty pharmacy selected by Amgen to dispense the product.

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FDA Approves First Targeted Therapy for Lung Cancer Mutation Previously Considered Resistant to Drug Therapy

May 28, 2021 — Today, the U.S. Food and Drug Administration approved Lumakras (sotorasib) as the first treatment for adult patients with non-small cell lung cancer whose tumors have a specific type of genetic mutation called KRAS G12C and who have received at least one prior systemic therapy. This is the first approved targeted therapy for tumors with any KRAS mutation, which accounts for approximately 25% of mutations in non-small cell lung cancers. KRAS G12C mutations represent about 13% of mutations in non-small cell lung cancers.

“KRAS mutations have long been considered resistant to drug therapy, representing a true unmet need for patients with certain types of cancer,” said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research. “Today’s approval represents a significant step towards a future where more patients will have a personalized treatment approach.”

Lung cancer, the most common cancer type with the highest mortality, can largely be categorized by the genetic mutations that cause it. KRAS is a type of mutation in a group of genes that help regulate cell growth and division.

Researchers evaluated the efficacy of Lumakras in a study of 124 patients with locally advanced or metastatic KRAS G12C-mutated non-small cell lung cancer with disease progression after receiving an immune checkpoint inhibitor and/or platinum-based chemotherapy. The major outcomes measured were objective response rate (proportion of patients whose tumor is destroyed or reduced) and duration of response. The objective response rate was 36% and 58% of those patients had a duration of response of six months or longer.

The approved 960 milligram dose is based on available clinical data, as well as pharmacokinetic and pharmacodynamic modeling that support the approved dose. As part of the evaluation for this accelerated approval, the agency is requiring a postmarketing trial to investigate whether a lower dose will have a similar clinical effect.

The most common side effects of Lumakras include diarrhea, musculoskeletal pain, nausea, fatigue, liver damage and cough. Lumakras should be withheld if patients develop symptoms of interstitial lung disease and permanently discontinued if interstitial lung disease is confirmed. Health care professionals should monitor a patient’s liver function tests prior to starting and when taking Lumakras. If a patient develops liver damage, Lumakras should be withheld, dose reduced or permanently discontinued. Patients should avoid taking acid-reducing agents, drugs that induce or are substrates for certain enzymes in the liver and drugs that are substrates of the P-glycoprotein while taking Lumakras.

Lumakras was approved using the Accelerated Approval pathway, under which the FDA may approve drugs for serious conditions where there is unmet medical need and a drug is shown to have certain effects that are reasonably likely to predict a clinical benefit to patients. Further study is required to verify and describe anticipated clinical benefits of Lumakras.

The FDA granted this application Fast Track, Priority Review and Breakthrough Therapy designations.

Lumakras also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with the Australian Therapeutic Goods Administration (TGA), the Brazilian Health Regulatory Agency (ANVISA), Health Canada and Medicines and Healthcare products Regulatory Agency (MHRA; United Kingdom). The application reviews are ongoing at the other regulatory agencies.

The FDA granted approval of Lumakras to Amgen Inc.