Month: June 2021

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.

The FDA approval of the new therapy for Alzheimer’s is like no other in recent memory and has generated a firestorm reaction from both supporters and opponents.

Public Comments include…..
Cons: “The proof of efficacy just isn’t there!” and “The clinical benefit was barely detectable!”
Pros: “Finally my mother has hope.” and “We now have something to offer our patients who have been waiting years for a new therapy.”

The new once-monthly, infused drug is Aduhelm (aducanumab) from Biogen. It is easy to understand desperate patients and families wanting hope, but, members of the FDA advisory panel were not convinced. None voted to support the approval and three members have since resigned in protest. The FDA did mandate a post -launch clinical trial, however. Biogen, and its partner Esai, now have until 2029 to complete that trial to confirm the drug’s benefits for Alzheimer’s patients. That did not impress the advisory panel members and a very large number of medical experts nationally.

At the crux of the matter, Aduhelm hasn’t been shown to help slow the brain-destroying disease. A reassessment of data from only one trial arm showed statistically small slowing of declines in cognition and day-to-day function. A Biogen statement suggested that even for those for whom it has little or no effect, it offers that hope consumers are demanding. “Hope is a good thing.” That argument seems to have saved the day for Biogen.

Why such pressure to offer hope?
The last therapy approved for Alzheimer’s was 18 years ago. Alzheimer’s gradually attacks areas of the brain needed for memory, reasoning, communication and basic daily tasks. It’s the most common cause of dementia and the sixth leading cause of death in this country. After diagnosis, senior patients only live four to eight years, on average. So, the approval of a new any drug is a spark of hope.

But, that hope comes at a cost.
First, about 35 percent of all trial patients experienced painful brain swelling and, in some cases, bleeding in the brain.
Second, the therapy will hit the market with a price tag of $56,000 annually. Much of the media coverage in recent days has speculated about how payers will cover the drug. For example, Medicare Part B is expected to cost patients upwards of $11,000 annually out-of-pocket.

Biogen estimates that about 1.4 million people would be eligible to be treated by Aduhelm. Let’s assume that only 5% of these patients receive Aduhelm therapy. In that case, Biogen sales could hit upwards of $4 billion annually! According to Biogen about 900 U.S. medical facilities are ready to begin prescribing the drug, with many more expected.

Biogen did not announce distribution details. However, we are already hearing that a handful of specialty pharmacies will be integral to channel access. If a limited distribution program (direct to provider) is adopted, those specialty pharmacies may be realizing a huge revenue tsunami in coming months.

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FDA Grants Accelerated Approval for Alzheimer’s Drug

June 07, 2021 — Today, the U.S. Food and Drug Administration approved Aduhelm (aducanumab) for the treatment of Alzheimer’s, a debilitating disease affecting 6.2 million Americans. Aduhelm was approved using the accelerated approval pathway, which can be used for a drug for a serious or life-threatening illness that provides a meaningful therapeutic advantage over existing treatments. Accelerated approval can be based on the drug’s effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients, with a required post-approval trial to verify that the drug provides the expected clinical benefit.

“Alzheimer’s disease is a devastating illness that can have a profound impact on the lives of people diagnosed with the disease as well as their loved ones,” said Patrizia Cavazzoni, M.D., director of the FDA’s Center for Drug Evaluation and Research. “Currently available therapies only treat symptoms of the disease; this treatment option is the first therapy to target and affect the underlying disease process of Alzheimer’s. As we have learned from the fight against cancer, the accelerated approval pathway can bring therapies to patients faster while spurring more research and innovation.”

Alzheimer’s is an irreversible, progressive brain disorder that slowly destroys memory and thinking skills, and eventually, the ability to carry out simple tasks. While the specific causes of Alzheimer’s disease are not fully known, it is characterized by changes in the brain—including amyloid plaques and neurofibrillary, or tau, tangles—that result in loss of neurons and their connections. These changes affect a person’s ability to remember and think.

Aduhelm represents a first-of-its-kind treatment approved for Alzheimer’s disease. It is the first new treatment approved for Alzheimer’s since 2003 and is the first therapy that targets the fundamental pathophysiology of the disease.

Researchers evaluated Aduhelm’s efficacy in three separate studies representing a total of 3,482 patients. The studies consisted of double-blind, randomized, placebo-controlled dose-ranging studies in patients with Alzheimer’s disease. Patients receiving the treatment had significant dose-and time-dependent reduction of amyloid beta plaque, while patients in the control arm of the studies had no reduction of amyloid beta plaque.

These results support the accelerated approval of Aduhelm, which is based on the surrogate endpoint of reduction of amyloid beta plaque in the brain—a hallmark of Alzheimer’s disease. Amyloid beta plaque was quantified using positron emission tomography (PET) imaging to estimate the brain levels of amyloid beta plaque in a composite of brain regions expected to be widely affected by Alzheimer’s disease pathology compared to a brain region expected to be spared of such pathology.

The prescribing information for Aduhelm includes a warning for amyloid-related imaging abnormalities (ARIA), which most commonly presents as temporary swelling in areas of the brain that usually resolves over time and does not cause symptoms, though some people may have symptoms such as headache, confusion, dizziness, vision changes, or nausea. Another warning for Aduhelm is for a risk of hypersensitivity reactions, including angioedema and urticaria. The most common side effects of Aduhelm were ARIA, headache, fall, diarrhea, and confusion/delirium/altered mental status/disorientation.

Under the accelerated approval provisions, which provide patients suffering from the disease earlier access to the treatment, the FDA is requiring the company, Biogen, to conduct a new randomized, controlled clinical trial to verify the drug’s clinical benefit. If the trial fails to verify clinical benefit, the FDA may initiate proceedings to withdraw approval of the drug.

Aduhelm was granted Fast Track designation, which seeks to expedite the development and review of drugs that are intended to treat serious conditions where initial evidence showed the potential to address an unmet medical need.

Aduhelm is made by Biogen of Cambridge, Massachusetts.

Here’s something that you don’t see every day….. CVS has announced that it is opening a new division to provide Clinical Trial Services. Yep, the whole magilla, including patient recruitment.

So, are clinical trial services a good fit for CVS? In short, yes.

With the number of new therapies growing exponentially the need for effective clinical trial management partners are top of mind with manufacturers. There are many CRO / Clinical Trial companies, but demand is now exceeding supply. Also, the track record for established companies is less than stellar. Participant recruitment and retention prevent many trials from finishing successfully. Upwards of 80% of studies don’t meet participant enrollment deadlines, and around 30% of participants drop out before a study is completed due to reasons ranging from inconvenient site location, complex participation requirements, and trial duration.

CVS has some limited experience with clinical trials and offers some good results to showcase. One example includes CVS’ infusion subsidiary, Coram. That particular trial achieved a patient retention rate close to 90% – well over the 70% average rate – due to Coram’s integrated position as the home care / infusion & enteral nutrition provider for the trial participants.

CVS can fast-track recruitment by tapping into its massive customer base as pharmacy benefit manager, its national retail pharmacy network, and its insurance business to find eligible patients. The cherry on the top is that 75% of people in the US live within 3 miles of a CVS store, which boosts accessibility….. about 40% of patients say that distance from trial sites and schedule conflicts are top reasons for dropping out.

But….. the there is one huge reason to use clinical trials as a way to get in on the ground level with manufactures….. CVS can increase its chances of being selected as the HUB provider, and/or the exclusive or a select specialty pharmacy if the product launches through limited distribution.
A good example of having one’s cake and eating it too!

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CVS Health Introduces Clinical Trial Services

The new business is uniquely positioned to continue delivering research solutions for COVID-19 and beyond with community presence, data capabilities and health care expertise

WOONSOCKET, R.I., May 20, 2021 /PRNewswire/ — Clinical trials are critical in evaluating the safety and efficacy of investigational new drugs and devices and making them available to those who need them. Despite their importance, less than 4 percent of the U.S. population participates in clinical studies. In addition, 80 percent of studies don’t meet participant enrollment deadlines, and an average of 30 percent of participants drop out before a study is completed.1 CVS Health (NYSE: CVS) today announced its new Clinical Trial Services business that brings together innovation and experience to help solve these challenges, driving greater access to clinical trials across the communities it serves and creating a more efficient, convenient experience to improve participant retention and research effectiveness.

CVS Health
“Traditionally low patient enrollment, diversity and engagement coupled with inconvenient trial sites, challenging study participation requirements, including the length of participation, show the need to improve the current model – particularly in response to the COVID-19 pandemic,” said Troyen A. Brennan, M.D., MPH, Executive Vice President and Chief Medical Officer of CVS Health. “Combining clinical trial expertise from across the CVS Health enterprise with our growing connection to the communities we serve, will help create a new clinical trial experience that works better for participants, health care providers, clinical research organizations and study sponsors.”

CVS Health Clinical Trial Services is working with key stakeholders in the biopharmaceutical industry and across the clinical trial ecosystem to design and deliver innovative approaches to research and real-world evidence generation. The new business will initially focus on scaling three core capabilities:

Precision patient recruitment: Leveraging analytics, national reach, and local community connections to engage individuals by helping them learn about clinical trial opportunities that may be appropriate for them
Clinical trial delivery: Innovative, decentralized options for the delivery of Phase III/IV clinical trials and real-world evidence studies at CVS locations, at home or virtually
Real-world evidence generation and studies: Retrospective and prospective studies that measure the impact of novel devices and therapeutics in real-world settings
CVS Health collaborated with the pharmaceutical industry to help facilitate clinical trials for investigational COVID-19 vaccines and treatments. Using a specially designed digital model and screening protocols, CVS Health engaged more than 300,000 volunteers who met the study inclusion criteria for COVID-19 vaccine trial consideration and helped them connect to studies close to where they live.

The Clinical Trial Services business will continue to use CVS Health’s expertise in both health care services and clinical research, including more than 200 in-home clinical trials, real-world evidence studies, and support for publication of peer-reviewed articles.

The FDA recently approved a new Specialty Infusion therapy, Rybrevant (amivantamab-vmjw) from Janssen Pharmaceutical, as the first treatment for adult patients with non-small cell lung cancer (NSCLC) with specific genetic mutations.

Infused specialty therapies were once relegated only to the medical benefit and traditional buy-and-bill. However, Rybrevant’s approval continues the growing trend that has created an integral role for specialty pharmacies supporting distribution under the medical benefit or direct-to-office using PBM billing (payer specific).

As with many of these next generation therapies, Rybrevant was approved in combination with a companion diagnostic test to identify targeted EGFR exon 20 mutations. This group represents only 2 or 3 percent of NSCLC patients.

Pricing for Rybrevant has not yet been confirmed by Janssen. Additionally, Janssen has not announced its plans for distribution and pharmacy access once the product launches. Analysts have indicated that its expected cost, the very small patient population, and need for genetic testing will push this therapy into limited distribution.

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FDA Approves First Targeted Therapy for Subset of Non-Small Cell Lung Cancer

May 21, 2021 — Today, the U.S. Food and Drug Administration approved Rybrevant (amivantamab-vmjw) as the first treatment for adult patients with non-small cell lung cancer whose tumors have specific types of genetic mutations: epidermal growth factor receptor (EGFR) exon 20 insertion mutations.

The FDA also approved the Guardant360 CDx (Guardant Health Inc.) as a companion diagnostic for Rybrevant today.

“Advances in precision oncology continue to facilitate drug development, allowing diseases like lung cancer to be subset into biomarker-defined populations appropriate for targeted therapies,” said Julia Beaver, M.D., chief of medical oncology in the FDA’s Oncology Center of Excellence and acting deputy director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research.

Lung cancer is the most common cancer type and the leading cause of cancer-related deaths worldwide, with non-small cell lung cancer accounting for 80% to 85% of all lung cancers, according to the American Cancer Society. Approximately 2% to 3% of patients with non-small cell lung cancer will have EGFR exon 20 insertion mutations, which are a group of mutations on a protein that causes rapid cell growth, and consequently, helps cancer spread. EGFR exon 20 insertion mutations are the third most common type of EGFR mutation.

Researchers evaluated Rybrevant’s efficacy in a study of 81 patients with non-small cell lung cancer and EGFR exon 20 insertion mutations whose disease had progressed on or after platinum-based chemotherapy. The main outcome measured was overall response rate (proportion of patients whose tumor is destroyed or reduced by a drug). In the trial population in which all patients received Rybrevant, the overall response rate was 40%. The median duration of response was 11.1 months, with 63% of patients having a duration of response of 6 months or more.

The most common side effects of Rybrevant include rash, infusion-related reactions, skin infections around the fingernails or toenails, muscle and joint pain, shortness of breath, nausea, fatigue, swelling in the lower legs or hands or face, sores in the mouth, cough, constipation, vomiting and changes in certain blood tests. Rybrevant should be withheld if patients develop symptoms of interstitial lung disease and permanently discontinued if interstitial lung disease is confirmed. Patients taking Rybrevant should limit sun exposure during and for two months after treatment. Rybrevant may cause problems with vision. Rybrevant can also cause fetal harm when administered to a pregnant woman; therefore, the pregnancy status of females of reproductive potential should be confirmed before treatment is started.

Rybrevant received Priority Review and Breakthrough Therapy designation for this indication. Priority Review directs overall attention and resources to the evaluation of applications for drugs that, if approved, would be significant improvements in the safety or effectiveness of the treatment, diagnosis or prevention of serious conditions when compared to standard applications. Breakthrough Therapy designation is designed to expedite the development and review of drugs that are intended to treat a serious condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s).

The FDA granted approval of Rybrevant to Janssen Pharmaceutical Companies of Johnson & Johnson.